Biological activities and medicinal properties of Gokhru (Pedalium murex L.)

PubMed Central

Rajashekar, V; Rao, E Upender; P, Srinivas

2012-01-01

Bada Gokhru (Pedalium murex L.) is perhaps the most useful traditional medicinal plant in India. Each part of the neem tree has some medicinal property and is thus commercially exploitable. During the last five decades, apart from the chemistry of the Pedalium murex compounds, considerable progress has been achieved regarding the biological activity and medicinal applications of this plant. It is now considered as a valuable source of unique natural products for development of medicines against various diseases and also for the development of industrial products. This review gives a bird's eye view mainly on the biological activities of some of this compounds isolated, pharmacological actions of the extracts, clinical studies and plausible medicinal applications of gokharu along with their safety evaluation. PMID:23569975

Proliferative activity of elastin-like-peptides depends on charge and phase transition.

PubMed

Yuan, Yuan; Koria, Piyush

2016-03-01

Elastin-like-peptides (ELPs) are stimulus-responsive protein-based polymers and are attractive biomaterials due to their biocompatibility and unique properties. This study shows that in addition to their physical properties, ELPs have biological activities that are conducive to tissue regeneration. Specifically, we found that ELPs induce fibroblast proliferation via cell surface heparan sulfate proteoglycans (HSPG). Furthermore, our data suggests that ELP based materials with differential proliferative potential can be designed by controlling the interaction of ELPs with HSPGs by incorporating either hydrophobic or positively charged residues within the ELP sequence. Fibroblast proliferation is important for granulation tissue formation which is important in chronic wounds as well as in healing of other tissues. The customizable biological activity of ELPs coupled with their unique physical properties will enable us to design novel, sustainable and cost effective therapies for different tissue regeneration applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 697-706, 2016. © 2015 Wiley Periodicals, Inc.

Plant recognition of Bradyrhizobium japonicum nod factors. Final report, September 15, 1992--March 14, 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stacey, G.

1998-01-01

This grant had three objectives: (1) isolate and identify the unique nod factor metabolites made by different wild-type B. japonicum strains; (2) investigate the biological activity of these unique nod factors, especially as it relates to host range; and (3) initiate studies to define the mechanism of plant recognition of the nod factors. This report summarizes the results of this research.

Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell.

PubMed

Kagan, Herbert M; Li, Wande

2003-03-01

Lysyl oxidase (LO) plays a critical role in the formation and repair of the extracellular matrix (ECM) by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent crosslinkages which stabilize these fibrous proteins. Its catalytic activity depends upon both its copper cofactor and a unique carbonyl cofactor and has been shown to extend to a variety of basic globular proteins, including histone H1. Although the three-dimensional structure of LO has yet to be determined, the present treatise offers hypotheses based upon its primary sequence, which may underlie the prominent electrostatic component of its unusual substrate specificity as well as the catalysis-suppressing function of the propeptide domain of prolysyl oxidase. Recent studies have demonstrated that LO appears to function within the cell in a manner, which strongly modifies cellular activity. Newly discovered LO-like proteins also likely play unique roles in biology. Copyright 2002 Wiley-Liss, Inc.

Molecular Architecture and Biomedical Leads of Terpenes from Red Sea Marine Invertebrates

PubMed Central

Hegazy, Mohamed Elamir F.; Mohamed, Tarik A.; Alhammady, Montaser A.; Shaheen, Alaa M.; Reda, Eman H.; Elshamy, Abdelsamed I.; Aziz, Mina; Paré, Paul W.

2015-01-01

Marine invertebrates including sponges, soft coral, tunicates, mollusks and bryozoan have proved to be a prolific source of bioactive natural products. Among marine-derived metabolites, terpenoids have provided a vast array of molecular architectures. These isoprenoid-derived metabolites also exhibit highly specialized biological activities ranging from nerve regeneration to blood-sugar regulation. As a result, intense research activity has been devoted to characterizing invertebrate terpenes from both a chemical and biological standpoint. This review focuses on the chemistry and biology of terpene metabolites isolated from the Red Sea ecosystem, a unique marine biome with one of the highest levels of biodiversity and specifically rich in invertebrate species. PMID:26006713

Biology and Systematics of Echinococcus.

PubMed

Thompson, R C A

2017-01-01

The biology of Echinococcus, the causative agent of echinococcosis (hydatid disease) is reviewed with emphasis on the developmental biology of the adult and metacestode stages of the parasite. Major advances include determining the origin, structure and functional activities of the laminated layer and its relationship with the germinal layer; and the isolation, in vitro establishment and characterization of the multipotential germinal cells. Future challenges are to identify the mechanisms that provide Echinococcus with its unique developmental plasticity and the nature of activities at the parasite-host interface, particularly in the definitive host. The revised taxonomy of Echinococcus is presented and the solid nomenclature it provides will be essential in understanding the epidemiology of echinococcosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical composition and biological activity of ripe pumpkin fruits (Cucurbita pepo L.) cultivated in Egyptian habitats.

PubMed

Badr, Sherif E A; Shaaban, Mohamed; Elkholy, Yehya M; Helal, Maher H; Hamza, Akila S; Masoud, Mohamed S; El Safty, Mounir M

2011-09-01

The chemical composition and biological activity of three parts (rind, flesh and seeds) of pumpkin fruits (Cucurbita pepo L.) cultivated in Egypt were studied. Chemical analysis of fibre, protein, β-carotene, carbohydrates, minerals and fatty acids present in the rind, flesh, seeds and defatted seeds meal was conducted. Chemical, GC-MS and biological assays of organic extracts of the main fruit parts, rind and flesh established their unique constituents. Chromatographic purification of the extracts afforded triglyceride fatty acid mixture (1), tetrahydro-thiophene (2), linoleic acid (3), calotropoleanly ester (4), cholesterol (5) and 13(18)-oleanen-3-ol (6). GC-MS analysis of the extract's unpolar fraction revealed the existence of dodecane and tetradecane. Structures of the isolated compounds (1-6) were confirmed by NMR and EI-MS spectrometry. Antimicrobial, antiviral and antitumour activities of the fruit parts were discussed. The promising combined extract of rind and flesh was biologically studied for microbial and cytotoxic activities in comparison with the whole isolated components.

20180129 - Computational Embryology: Translational Tools for Modeling in vitro Data (Toxicology Forum)

EPA Science Inventory

Integrative models are needed to "decode the toxicological blueprint of active substances that interact with living systems" (Systems toxicology). Computational biology is uniquely positioned to capture this connectivity and help shift decision-making to mechanistic pre...

Monolithic graphene transistor biointerface.

PubMed

Nam, SungWoo; Lee, Mi-Sun; Park, Jang-Ung

2012-01-01

We report monolithic integration of graphene and graphite for all-carbon integrated bioelectronics. First, we demonstrate that the electrical properties of graphene and graphite can be modulated by controlling the number of graphene layers, and such capabilities allow graphene to be used as active channels and graphite as metallic interconnects for all-carbon bioelectronics. Furthermore, we show that monolithic graphene-graphite devices exhibit mechanical flexibility and robustness while their electrical responses are not perturbed by mechanical deformation, demonstrating their unique electromechanical properties. Chemical sensing capability of all-carbon integrated bioelectronics is manifested in real-time, complementary pH detection. These unique capabilities of our monolithic graphene-graphite bioelectronics could be exploited in chemical and biological detection and conformal interface with biological systems in the future.

Marine natural flavonoids: chemistry and biological activities.

PubMed

Martins, Beatriz T; Correia da Silva, Marta; Pinto, Madalena; Cidade, Honorina; Kijjoa, Anake

2018-05-04

As more than 70% of the world's surface is covered by oceans, marine organisms offer a rich and unlimited resource of structurally diverse bioactive compounds. These organisms have developed unique properties and bioactive compounds that are, in majority of them, unparalleled by their terrestrial counterparts due to the different surrounding ecological systems. Marine flavonoids have been extensively studied in the last decades due to a growing interest concerning their promising biological/pharmacological activities. The most common classes of marine flavonoids are flavones and flavonols, which are mostly isolated from marine plants. Although most of flavonoids are hydroxylated and methoxylated, some marine flavonoids possess an unusual substitution pattern, not commonly found in terrestrial organisms, namely the presence of sulphate, chlorine, and amino groups. This review presents, for the first time in a systematic way, the structure, natural occurrence, and biological activities of marine flavonoids.

Proteomic characterisation of toxins isolated from nematocysts of the South Atlantic jellyfish Olindias sambaquiensis.

PubMed

Weston, Andrew J; Chung, Ray; Dunlap, Walter C; Morandini, André C; Marques, Antonio C; Moura-da-Silva, Ana M; Ward, Malcolm; Padilla, Gabriel; da Silva, Luiziana Ferreira; Andreakis, Nikos; Long, Paul F

2013-09-01

Surprisingly little is known of the toxic arsenal of cnidarian nematocysts compared to other venomous animals. Here we investigate the toxins of nematocysts isolated from the jellyfish Olindias sambaquiensis. A total of 29 unique ms/ms events were annotated as potential toxins homologous to the toxic proteins from diverse animal phyla, including cone-snails, snakes, spiders, scorpions, wasp, bee, parasitic worm and other Cnidaria. Biological activities of these potential toxins include cytolysins, neurotoxins, phospholipases and toxic peptidases. The presence of several toxic enzymes is intriguing, such as sphingomyelin phosphodiesterase B (SMase B) that has only been described in certain spider venoms, and a prepro-haystatin P-IIId snake venom metalloproteinase (SVMP) that activates coagulation factor X, which is very rare even in snake venoms. Our annotation reveals sequence orthologs to many representatives of the most important superfamilies of peptide venoms suggesting that their origins in higher organisms arise from deep eumetazoan innovations. Accordingly, cnidarian venoms may possess unique biological properties that might generate new leads in the discovery of novel pharmacologically active drugs. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Exploring Biological Classification: The Unique Organism Project

ERIC Educational Resources Information Center

Haines, Sarah; Richman, Laila; Hartley, Renee; Schmid, Rachel

2017-01-01

The unique organism project was designed as a culminating assessment for a biological classification unit in a middle school setting. Students developed a model to represent their unique organism. Using the model, students were required to demonstrate how their unique organism interacts with its environment, and how its internal and external…

Investigating the Relationship between Instructors’ Use of Active-Learning Strategies and Students’ Conceptual Understanding and Affective Changes in Introductory Biology: A Comparison of Two Active-Learning Environments

PubMed Central

Cleveland, Lacy M.; Olimpo, Jeffrey T.; DeChenne-Peters, Sue Ellen

2017-01-01

In response to calls for reform in undergraduate biology education, we conducted research examining how varying active-learning strategies impacted students’ conceptual understanding, attitudes, and motivation in two sections of a large-lecture introductory cell and molecular biology course. Using a quasi-experimental design, we collected quantitative data to compare participants’ conceptual understanding, attitudes, and motivation in the biological sciences across two contexts that employed different active-learning strategies and that were facilitated by unique instructors. Students participated in either graphic organizer/worksheet activities or clicker-based case studies. After controlling for demographic and presemester affective differences, we found that students in both active-learning environments displayed similar and significant learning gains. In terms of attitudinal and motivational data, significant differences were observed for two attitudinal measures. Specifically, those students who had participated in graphic organizer/worksheet activities demonstrated more expert-like attitudes related to their enjoyment of biology and ability to make real-world connections. However, all motivational and most attitudinal data were not significantly different between the students in the two learning environments. These data reinforce the notion that active learning is associated with conceptual change and suggests that more research is needed to examine the differential effects of varying active-learning strategies on students’ attitudes and motivation in the domain. PMID:28389428

AtPDS over-expression in tomato: exposing unique patterns of carotenoid self-regulation and an alternative strategy for the enhancement of fruit carotenoid content

USDA-ARS?s Scientific Manuscript database

The regulation of plant carotenogenesis is an active research area for both biological discovery and practical implementation. In tomato, we demonstrate additional bottlenecks exist in the poly-cis-transformation of phytoene to lycopene in the context of ripening-induced PSY1 expression and activity...

Plant defense activators as elicitors of oat avenanthramide biosynthesis

USDA-ARS?s Scientific Manuscript database

Oats produce a group of phenolic secondary metabolites termed “avenanthramides”. Among food crops these metabolites are unique to oat. In addition to their biological role as phytoalexins, the avenanthramides are potent antioxidants in vitro and have potential as nutraceuticals. In cellular assays ...

Conformationally Constrained Analogues of Diacylglycerol. 29. Cells Sort Diacylglycerol-Lactone Chemical Zip Codes to Produce Diverse and Selective Biological Activities

PubMed Central

Duan, Dehui; Sigano, Dina M.; Kelley, James A.; Lai, Christopher C.; Lewin, Nancy E.; Kedei, Noemi; Peach, Megan L.; Lee, Jeewoo; Abeyweera, Thushara P.; Rotenberg, Susan A.; Kim, Hee; Kim, Young Ho; Kazzouli, Saïd El; Chung, Jae-Uk; Young, Howard A.; Young, Matthew R.; Baker, Alyson; Colburn, Nancy H.; Haimovitz-Friedman, Adriana; Truman, Jean-Philip; Parrish, Damon A.; Deschamps, Jeffrey R.; Perry, Nicholas A.; Surawski, Robert J.; Blumberg, Peter M.; Marquez, Victor E.

2008-01-01

Diacylglycerol-lactone (DAG-lactone) libraries generated by a solid-phase approach using IRORI technology produced a variety of unique biological activities. Subtle differences in chemical diversity in two areas of the molecule, the combination of which generates what we have termed “chemical zip codes”, are able to transform a relatively small chemical space into a larger universe of biological activities, as membrane-containing organelles within the cell appear to be able to decode these “chemical zip codes”. It is postulated that after binding to protein kinase C (PKC) isozymes or other non-kinase target proteins that contain diacylglycerol responsive, membrane interacting domains (C1 domains), the resulting complexes are directed to diverse intracellular sites where different sets of substrates are accessed. Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCα to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses. PMID:18698758

BioArena studies: unique function of endogenous formaldehyde and ozone in the antibiotic effect--a review.

PubMed

Tyihák, Erno; Móricz, Agnes M; Ott, Péter G

2012-01-01

The investigations demonstrated clearly a unique function and role of endogenous formaldehyde (HCHO) and ozone (O3) in the antibiotic effect of diverse molecules having different chemical structure. Elimination of HCHO and/or O3 from the layer chromatographic spots resulted in a decrease in the antimicrobial activity. On the basis of detection and measure of endogenous HCHO and O3 BioArena enables to both direct isolation and biological evaluation of new bioactive compounds.

An integrated cell-free metabolic platform for protein production and synthetic biology

PubMed Central

Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

2008-01-01

Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements. PMID:18854819

Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity.

PubMed Central

Basu, S; Mandal, C; Allen, A K

1988-01-01

A unique sialic acid-binding lectin, achatininH (ATNH) was purified in single step from the haemolymph of the snail Achatina fulica by affinity chromatography on sheep submaxillary-gland mucin coupled to Sepharose 4B. The homogeneity was checked by alkaline gel electrophoresis, immunodiffusion and immunoelectrophoresis. Amino acid analysis showed that the lectin has a fairly high content of acidic amino acid residues (22% of the total). About 1.3% of the residues are half-cystine. The glycoprotein contains 21% carbohydrate. The unusually high content of xylose (6%) and fucose (2.7%) in this snail lectin is quite interesting. The protein was subjected to various chemical modifications in order to detect the amino acid residues and carbohydrate residues present in its binding sites. Modification of tyrosine and arginine residues did not affect the binding activity of ATNH; however, modification of tryptophan and histidine residues led to a complete loss of its biological activity. A marked decrease in the fluorescence emission was found as the tryptophan residues of ATNH were modified. The c.d. data showed the presence of an identical type of conformation in the native and modified agglutinin. The modification of lysine and carboxy residues partially diminished the biological activity. The activity was completely lost after a beta-elimination reaction, indicating that the sugars are O-glycosidically linked to the glycoprotein's protein moiety. This result confirms that the carbohydrate moiety also plays an important role in the agglutination property of this lectin. Images Fig. 3. PMID:3140796

Optically active biological particle distinguishing apparatus

DOEpatents

Salzman, Gary C.; Kupperman, Robert H.

1989-01-01

The disclosure is directed to organic particle sorting and identification. High frequency pulses of circularly polarized light, alternating between left and right, intersect a fast moving stream of organic particles. Circular intensity differential scattering and linear intensity differential scattering are monitored to uniquely identify a variety of organic particles.

Anticancer effect and structure-activity analysis of marine products isolated from metabolites of mangrove fungi in the South China Sea.

PubMed

Tao, Li-yang; Zhang, Jian-ye; Liang, Yong-ju; Chen, Li-ming; Zhen, Li-sheng; Wang, Fang; Mi, Yan-jun; She, Zhi-gang; To, Kenneth Kin Wah; Lin, Yong-cheng; Fu, Li-wu

2010-04-01

Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.

Seafloor massive sulfide deposits support unique megafaunal assemblages: Implications for seabed mining and conservation.

PubMed

Boschen, Rachel E; Rowden, Ashley A; Clark, Malcolm R; Pallentin, Arne; Gardner, Jonathan P A

2016-04-01

Mining of seafloor massive sulfides (SMS) is imminent, but the ecology of assemblages at SMS deposits is poorly known. Proposed conservation strategies include protected areas to preserve biodiversity at risk from mining impacts. Determining site suitability requires biological characterisation of the mine site and protected area(s). Video survey of a proposed mine site and protected area off New Zealand revealed unique megafaunal assemblages at the mine site. Significant relationships were identified between assemblage structure and environmental conditions, including hydrothermal features. Unique assemblages occurred at both active and inactive chimneys and are particularly at risk from mining-related impacts. The occurrence of unique assemblages at the mine site suggests that the proposed protected area is insufficient alone and should instead form part of a network. These results provide support for including hydrothermally active and inactive features within networks of protected areas and emphasise the need for quantitative survey data of proposed sites. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Extending human perception of electromagnetic radiation to the UV region through biologically inspired photochromic fuzzy logic (BIPFUL) systems.

PubMed

Gentili, Pier Luigi; Rightler, Amanda L; Heron, B Mark; Gabbutt, Christopher D

2016-01-25

Photochromic fuzzy logic systems have been designed that extend human visual perception into the UV region. The systems are founded on a detailed knowledge of the activation wavelengths and quantum yields of a series of thermally reversible photochromic compounds. By appropriate matching of the photochromic behaviour unique colour signatures are generated in response differing UV activation frequencies.

Ion-driven photoluminescence modulation of quasi-two-dimensional MoS2 nanoflakes for applications in biological systems.

PubMed

Ou, Jian Zhen; Chrimes, Adam F; Wang, Yichao; Tang, Shi-yang; Strano, Michael S; Kalantar-zadeh, Kourosh

2014-02-12

Quasi-two-dimensional (quasi-2D) molybdenum disulfide (MoS2) is a photoluminescence (PL) material with unique properties. The recent demonstration of its PL, controlled by the intercalation of positive ions, can lead to many opportunities for employing this quasi-2D material in ion-related biological applications. Here, we present two representative models of biological systems that incorporate the ion-controlled PL of quasi-2D MoS2 nanoflakes. The ion exchange behaviors of these two models are investigated to reveal enzymatic activities and cell viabilities. While the ion intercalation of MoS2 in enzymatic activities is enabled via an external applied voltage, the intercalation of ions in cell viability investigations occurs in the presence of the intrinsic cell membrane potential.

Investigating the Relationship between Instructors' Use of Active-Learning Strategies and Students' Conceptual Understanding and Affective Changes in Introductory Biology: A Comparison of Two Active-Learning Environments.

PubMed

Cleveland, Lacy M; Olimpo, Jeffrey T; DeChenne-Peters, Sue Ellen

2017-01-01

In response to calls for reform in undergraduate biology education, we conducted research examining how varying active-learning strategies impacted students' conceptual understanding, attitudes, and motivation in two sections of a large-lecture introductory cell and molecular biology course. Using a quasi-experimental design, we collected quantitative data to compare participants' conceptual understanding, attitudes, and motivation in the biological sciences across two contexts that employed different active-learning strategies and that were facilitated by unique instructors. Students participated in either graphic organizer/worksheet activities or clicker-based case studies. After controlling for demographic and presemester affective differences, we found that students in both active-learning environments displayed similar and significant learning gains. In terms of attitudinal and motivational data, significant differences were observed for two attitudinal measures. Specifically, those students who had participated in graphic organizer/worksheet activities demonstrated more expert-like attitudes related to their enjoyment of biology and ability to make real-world connections. However, all motivational and most attitudinal data were not significantly different between the students in the two learning environments. These data reinforce the notion that active learning is associated with conceptual change and suggests that more research is needed to examine the differential effects of varying active-learning strategies on students' attitudes and motivation in the domain. © 2017 L. M. Cleveland et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

DOE Office of Scientific and Technical Information (OSTI.GOV)

BECHTEL NEVADA ECOLOGICAL SERVICES

The Ecological Monitoring and Compliance program (EMAC), funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO), monitors the ecosystem of the Nevada Test Site (NTS) and ensures compliance with laws and regulations pertaining to NTS biota. This report summarizes the program’s activities conducted by Bechtel Nevada (BN) during the Calendar Year 2005. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive and protected/regulated species and unique habitat monitoring, (5) habitat restoration monitoring, and (6) biological monitoring at the Non-Proliferation Test andmore » Evaluation Complex (NPTEC).« less

Haberlea rhodopensis: pharmaceutical and medical potential as a food additive.

PubMed

Todorova, Roumiana; Atanasov, Atanas T

2016-01-01

This review discusses the potential of Haberlea rhodopensis as a food additive. The following are described: plant distribution, reproduction, cultivation, propagation and resurrection properties; extraction, isolation and screening of biologically active compounds; metabolite changes during dehydration; phytotherapy-related properties such as antioxidant potential and free radical-scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic activity and cancer-modulating effect, radioprotective effect, chemoprotective effect, immunologic effect; present use in homoeopathy and cosmetics, pharmacological and economical importance; perspectives based on the ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis showed unique medical and pharmaceutical potential, related to antioxidant, antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and immunological properties. H. rhodopensis extracts lack any cytotoxic activity and could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts revealed the presence of biologically active compounds, possessing antiradical and other physiological activities, useful for design of in vitro synthesised analogues and drugs.

Substitution on the A-Ring Confers to Bryopyran Analogues the Unique Biological Activity Characteristic of Bryostatins and Distinct From That of the Phorbol Esters

PubMed Central

Keck, Gary E.; Poudel, Yam B.; Welch, Dennie S.; Kraft, Matthew B.; Truong, Anh P.; Stephens, Jeffrey C.; Kedei, Noemi; Lewin, Nancy E.; Blumberg, Peter M.

2009-01-01

A close structural analogue of bryostatin 1, which differs from bryostatin 1 only by the absence of the C30 carbomethoxy group (on the C13 enoate of the B-ring), has been prepared by total synthesis. Biological assays reveal a crucial role for substitution in the bryostatin 1 A-ring in conferring those responses which are characteristic of bryostatin 1 and distinct from those observed with PMA. PMID:19113896

Microwave Digestion and Furnace Atomic Absorption Method for the Quantification of Nano-scale TiO2 in Aqueous Samples

EPA Science Inventory

Many nanomaterials posses physical, and potentially biological, activity that is unique relative to their macro-scaled or soluble forms. One such property is surface plasmon resonance; a phenomenon that can generate or facilitate photoreactivity. Optimization of these properties ...

Chemical and Biological Profiling Approaches for Exploring Mutagenicity and Carcinogenicity of EPA ToxCast Chemicals

EPA Science Inventory

Phase I of U.S. Environmental Protection Agency’s ToxCastTM research project is building on three rich data tiers: 309 unique, structurally diverse chemicals (predominantly pesticides), activity and concentration response data from approximately 500 in vitro (cell-based and cell-...

Axinellamines as Broad-Spectrum Antibacterial Agents: Scalable Synthesis and Biology

PubMed Central

2015-01-01

Antibiotic-resistant bacteria present an ongoing challenge to both chemists and biologists as they seek novel compounds and modes of action to out-maneuver continually evolving resistance pathways, especially against Gram-negative strains. The dimeric pyrrole–imidazole alkaloids represent a unique marine natural product class with diverse primary biological activity and chemical architecture. This full account traces the strategy used to develop a second-generation route to key spirocycle 9, culminating in a practical synthesis of the axinellamines and enabling their discovery as broad-spectrum antibacterial agents, with promising activity against both Gram-positive and Gram-negative bacteria. While their detailed mode of antibacterial action remains unclear, the axinellamines appear to cause secondary membrane destabilization and impart an aberrant cellular morphology consistent with the inhibition of normal septum formation. This study serves as a rare example of a natural product initially reported to be devoid of biological activity surfacing as an active antibacterial agent with an intriguing mode of action. PMID:25328977

Marine Antifreeze Proteins: Structure, Function, and Application to Cryopreservation as a Potential Cryoprotectant

PubMed Central

Kim, Hak Jun; Lee, Jun Hyuck; Hur, Young Baek; Lee, Chang Woo; Park, Sun-Ha; Koo, Bon-Won

2017-01-01

Antifreeze proteins (AFPs) are biological antifreezes with unique properties, including thermal hysteresis (TH), ice recrystallization inhibition (IRI), and interaction with membranes and/or membrane proteins. These properties have been utilized in the preservation of biological samples at low temperatures. Here, we review the structure and function of marine-derived AFPs, including moderately active fish AFPs and hyperactive polar AFPs. We also survey previous and current reports of cryopreservation using AFPs. Cryopreserved biological samples are relatively diverse ranging from diatoms and reproductive cells to embryos and organs. Cryopreserved biological samples mainly originate from mammals. Most cryopreservation trials using marine-derived AFPs have demonstrated that addition of AFPs can improve post-thaw viability regardless of freezing method (slow-freezing or vitrification), storage temperature, and types of biological sample type. PMID:28134801

Unique semantic space in the brain of each beholder predicts perceived similarity

PubMed Central

Charest, Ian; Kievit, Rogier A.; Schmitz, Taylor W.; Deca, Diana; Kriegeskorte, Nikolaus

2014-01-01

The unique way in which each of us perceives the world must arise from our brain representations. If brain imaging could reveal an individual’s unique mental representation, it could help us understand the biological substrate of our individual experiential worlds in mental health and disease. However, imaging studies of object vision have focused on commonalities between individuals rather than individual differences and on category averages rather than representations of particular objects. Here we investigate the individually unique component of brain representations of particular objects with functional MRI (fMRI). Subjects were presented with unfamiliar and personally meaningful object images while we measured their brain activity on two separate days. We characterized the representational geometry by the dissimilarity matrix of activity patterns elicited by particular object images. The representational geometry remained stable across scanning days and was unique in each individual in early visual cortex and human inferior temporal cortex (hIT). The hIT representation predicted perceived similarity as reflected in dissimilarity judgments. Importantly, hIT predicted the individually unique component of the judgments when the objects were personally meaningful. Our results suggest that hIT brain representational idiosyncrasies accessible to fMRI are expressed in an individual's perceptual judgments. The unique way each of us perceives the world thus might reflect the individually unique representation in high-level visual areas. PMID:25246586

Nanoelectronics Meets Biology: From Novel Nanoscale Devices for Live Cell Recording to 3D Innervated Tissues†

PubMed Central

Duan, Xiaojie; Lieber, Charles M.

2013-01-01

High spatio-temporal resolution interfacing between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. This focused review summarizes recent progresses in the development and application of novel nanoscale devices for intracellular electrical recordings of action potentials, and the effort of merging electronic and biological systems seamlessly in three dimension using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large scale, high spatial resolution, and three dimensional neural activity mapping will be highlighted. PMID:23946279

The relief of microtherm inhibition for p-fluoronitrobenzene mineralization using electrical stimulation at low temperatures.

PubMed

Zhang, Xueqin; Feng, Huajun; Liang, Yuxiang; Zhao, Zhiqing; Long, Yuyang; Fang, Yuan; Wang, Meizhen; Yin, Jun; Shen, Dongsheng

2015-05-01

Low temperature aggravates biological treatment of refractory p-fluoronitrobenzene (p-FNB) because of microtherm inhibition of microbial activity. Considering the potential characterization of energy supply for microbial metabolism and spurring microbial activity by electrical stimulation, a bioelectrochemical system (BES) was established to provide sustaining electrical stimulation for p-FNB mineralization at a low temperature. Electrical stimulation facilitated p-FNB treatment and bioelectrochemical reaction rate constants for the removal and defluorination of p-FNB at 10 °C were 0.0931 and 0.0054 h(-1), which were higher than the sums of the rates found using a biological system and an electrocatalytic system by 62.8 and 64.8%, respectively. At a low temperature, microbial activity in terms of dehydrogenase and ATPase was found to be higher with electrical stimulation, being 121.1 and 100.1% more active than that in the biological system. Moreover, stronger antioxidant ability was observed in the BES, which implied a better cold-resistance and relief of microtherm inhibition by electrical stimulation. Bacterial diversity analysis revealed a significant evolution of microbial community by electrical stimulation, and Clostridia was uniquely enriched. One bacterial sequence close to Pseudomonas became uniquely predominant, which appeared to be crucial for excellent p-FNB treatment performance in the BES at a low temperature. Economic evaluation revealed that the energy required to mineralize an extra mole of p-FNB was found to be 247 times higher by heating the system than by application of electrical stimulation. These results indicated that application of electrical stimulation is extremely promising for treating refractory waste at low temperatures.

Ligand Based-Pharmacophore Modeling and Extended Bi oactivity Prediction for Salinosporamide A, B and C from Marine Actino mycetes Salinispora tropica.

PubMed

Dineshkumar, Kesavan; Vasudevan, Aparna; Hopper, Waheeta

2017-01-01

Actinomycetes produce structurally unique secondary metabolites with pharmaceutically essential bioactivities. Salinispora, an obligate marine actinomycete, produces structurally varied and unique secondary metabolites. There is plenty of scope for development of drugs from the novel compounds isolated from Salinispora. Anticancer, antibacterial and anti-protozoa activities have been shown for Salinosporamides A, B and C, the secondary metabolites identified from Salinispora, which make them interesting subjects for further extended biological activity prediction. An in silico ligand based-pharmacophore approach was used for the prediction of extended biological targets for salinosporamide A, B and C. Pharmacophore models of salinosporamide A, B and C were generated individually and screened against known drug databases. The drugs with best fitness score were shortlisted, and their respective targets pertaining to their bioactivity were retrieved. The predicted biological drug targets were docked with salinosporamide A, B and C for validation. The glucocorticoid receptor and methionine aminopeptidase 2 showed good docking score and binding energy with salinosporamide A, B and C. Molecular dynamics studies of the protein-ligand complexes showed stable interactions suggesting that the predicted new targets for salinosporamides might be promising. The glucocorticoid receptor and methionine aminopeptidase 2 could be possible new drug targets of bioactivity of salinosporamides. These proteins could be the druggable targets for antiinflammatory and anticancer activity of salinosporamides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preparing the “New” Biologist of the Future: Student Research at the Interface of Mathematics and Biology

PubMed Central

Bishop, Pamela; Lenhart, Suzanne

2010-01-01

We describe a unique Research Experience for Undergraduates and Research Experience for Veterinary students summer program at the National Institute for Mathematical and Biological Synthesis on the campus of the University of Tennessee, Knoxville. The program focused on interdisciplinary research at the interface of biology and mathematics. Participants were selected to work on projects with a biology mentor and a mathematics mentor in an environment that promoted collaboration outside of the students' respective disciplines. There were four research projects with teams of four participants and two faculty mentors. The participants consisted of a mixture of 10 undergraduates in biology- and mathematics-related disciplines, four veterinary students, and two high-school teachers. The activities included lectures on both the biological and mathematical backgrounds of the projects, tutorials for software, and sessions on ethics, graduate school, and possible career paths for individuals interested in biology and mathematics. The program was designed to give students the ability to actively participate in the scientific research process by working on a project, writing up their results in a final report, and presenting their work orally. We report on the results of our evaluation surveys of the participants. PMID:20810963

Preparing the "new" biologist of the future: student research at the interface of mathematics and biology.

PubMed

Duncan, Sarah I; Bishop, Pamela; Lenhart, Suzanne

2010-01-01

We describe a unique Research Experience for Undergraduates and Research Experience for Veterinary students summer program at the National Institute for Mathematical and Biological Synthesis on the campus of the University of Tennessee, Knoxville. The program focused on interdisciplinary research at the interface of biology and mathematics. Participants were selected to work on projects with a biology mentor and a mathematics mentor in an environment that promoted collaboration outside of the students' respective disciplines. There were four research projects with teams of four participants and two faculty mentors. The participants consisted of a mixture of 10 undergraduates in biology- and mathematics-related disciplines, four veterinary students, and two high-school teachers. The activities included lectures on both the biological and mathematical backgrounds of the projects, tutorials for software, and sessions on ethics, graduate school, and possible career paths for individuals interested in biology and mathematics. The program was designed to give students the ability to actively participate in the scientific research process by working on a project, writing up their results in a final report, and presenting their work orally. We report on the results of our evaluation surveys of the participants.

The European Lead Factory: A Blueprint for Public-Private Partnerships in Early Drug Discovery.

PubMed

Karawajczyk, Anna; Orrling, Kristina M; de Vlieger, Jon S B; Rijnders, Ton; Tzalis, Dimitrios

2016-01-01

The European Lead Factory (ELF) is a public-private partnership (PPP) that provides researchers in Europe with a unique platform for translation of innovative biology and chemistry into high-quality starting points for drug discovery. It combines an exceptional collection of small molecules, high-throughput screening (HTS) infrastructure, and hit follow-up capabilities to advance research projects from both private companies and publicly funded researchers. By active interactions with the wider European life science community, ELF connects and unites bright ideas, talent, and experience from several disciplines. As a result, ELF is a unique, collaborative lead generation engine that has so far resulted in >4,500 hit compounds with a defined biological activity from 83 successfully completed HTS and hit evaluation campaigns. The PPP has also produced more than 120,000 novel innovative library compounds that complement the 327,000 compounds contributed by the participating pharmaceutical companies. Intrinsic to its setup, ELF enables breakthroughs in areas with unmet medical and societal needs, where no individual entity would be able to create a comparable impact in such a short time.

The European Lead Factory: A Blueprint for Public–Private Partnerships in Early Drug Discovery

PubMed Central

Karawajczyk, Anna; Orrling, Kristina M.; de Vlieger, Jon S. B.; Rijnders, Ton; Tzalis, Dimitrios

2017-01-01

The European Lead Factory (ELF) is a public–private partnership (PPP) that provides researchers in Europe with a unique platform for translation of innovative biology and chemistry into high-quality starting points for drug discovery. It combines an exceptional collection of small molecules, high-throughput screening (HTS) infrastructure, and hit follow-up capabilities to advance research projects from both private companies and publicly funded researchers. By active interactions with the wider European life science community, ELF connects and unites bright ideas, talent, and experience from several disciplines. As a result, ELF is a unique, collaborative lead generation engine that has so far resulted in >4,500 hit compounds with a defined biological activity from 83 successfully completed HTS and hit evaluation campaigns. The PPP has also produced more than 120,000 novel innovative library compounds that complement the 327,000 compounds contributed by the participating pharmaceutical companies. Intrinsic to its setup, ELF enables breakthroughs in areas with unmet medical and societal needs, where no individual entity would be able to create a comparable impact in such a short time. PMID:28154815

Nature Bank and the Queensland Compound Library: unique international resources at the Eskitis Institute for Drug Discovery.

PubMed

Camp, David; Newman, Stuart; Pham, Ngoc B; Quinn, Ronald J

2014-03-01

The Eskitis Institute for Drug Discovery is home to two unique resources, Nature Bank and the Queensland Compound Library (QCL), that differentiate it from many other academic institutes pursuing chemical biology or early phase drug discovery. Nature Bank is a comprehensive collection of plants and marine invertebrates that have been subjected to a process which aligns downstream extracts and fractions with lead- and drug-like physicochemical properties. Considerable expertise in screening natural product extracts/fractions was developed at Eskitis over the last two decades. Importantly, biodiscovery activities have been conducted from the beginning in accordance with the UN Convention on Biological Diversity (CBD) to ensure compliance with all international and national legislative requirements. The QCL is a compound management and logistics facility that was established from public funds to augment previous investments in high throughput and phenotypic screening in the region. A unique intellectual property (IP) model has been developed in the case of the QCL to stimulate applied, basic and translational research in the chemical and life sciences by industry, non-profit, and academic organizations.

Synthesis and biological evaluations of a series of thaxtomin analogues.

PubMed

Zhang, Hongbo; Wang, Qingpeng; Ning, Xin; Hang, Hang; Ma, Jing; Yang, Xiande; Lu, Xiaolin; Zhang, Jiabao; Li, Yonghong; Niu, Congwei; Song, Haoran; Wang, Xin; Wang, Peng George

2015-04-15

Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive structure-activity relationship study screens four effective compounds, including thaxtomin A and thaxtomin C. It is indicated that 4-nitro indole fragment is essential for phytotoxicity, while benzyl and m-hydroxybenzyl substituents on the diketopiperazine ring are favorable for the efficacy. The N-methylations on indole and diketopiperazine show weak influence on the herbicidal activities. The four selected compounds show effective herbicidal activities against Brassica campestris, Amaranthus retroflexus, and Abutilon theophrasti, which are comparable or better than dichlobenil, even at a dosage of 187.5 g ha(-1). Moreover, these four compounds show good crop-selective properties to different crops and exhibit moderate protoporphyrinogen oxidase (PPO) enzyme inhibition. The antifungal results indicate that thaxtomin C displays inhibition to a wide range of fungi.

Pop-it beads to introduce catalysis of reaction rate and substrate depletion effects.

PubMed

Gehret, Austin U

2017-03-04

A kinesthetic classroom activity was designed to help students understand enzyme activity and catalysis of reaction rate. Students served the role of enzymes by manipulating Pop-It Beads as the catalytic event. This activity illuminates the relationship between reaction rate and reaction progress by allowing students to experience first-hand the effect of substrate depletion on catalyzed reaction rate. Preliminary findings based on survey results and exam performance suggest the activity could prove beneficial to students in the targeted learning outcomes. Unique to previous kinesthetic approaches that model Michaelis-Menten kinetics, this activity models the effects of substrate depletion on catalyzed reaction rate. Therefore, it could prove beneficial for conveying the reasoning behind the initial rate simplification used in Michaelis-Menten kinetics. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(2):179-183, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy.

PubMed

Hamson, Elizabeth J; Keane, Fiona M; Tholen, Stefan; Schilling, Oliver; Gorrell, Mark D

2014-06-01

Fibroblast activation protein (FAP) is best known for its heightened expression in tumour stroma. This atypical serine protease has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. FAP expression is difficult to detect in non-diseased adult organs, but is greatly upregulated in sites of tissue remodelling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumours and embryonic tissues. Due to its restricted expression pattern and dual enzymatic activities, FAP is emerging as a unique therapeutic target. However, methods to exploit and target this protease are advancing more rapidly than knowledge of the fundamental biology of FAP. This review highlights this imbalance, emphasising the need to better define the substrate repertoire and expression patterns of FAP to elucidate its role in biological and pathological processes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of terahertz spectroscopy for characterization of biologically active organic molecules in natural environment

NASA Astrophysics Data System (ADS)

Karaliūnas, Mindaugas; Jakštas, Vytautas; Nasser, Kinan E.; Venckevičius, Rimvydas; Urbanowicz, Andrzej; Kašalynas, Irmantas; Valušis, Gintaras

2016-09-01

In this work, a comparative research of biologically active organic molecules in its natural environment using the terahertz (THz) time domain spectroscopy (TDS) and Fourier transform spectroscopy (FTS) systems is carried out. Absorption coefficient and refractive index of Nicotiana tabacum L. leaves containing nicotine, Cannabis sativa L. leaves containing tetrahydrocannabinol, and Humulu lupulus L. leaves containing α-acids, active organic molecules that obtain in natural environment, were measured in broad frequency range from 0.1 to 13 THz at room temperature. In the spectra of absorption coefficient the features were found to be unique for N. tabacum, C. sativa and H. lupulus. Moreover, those features can be exploited for identification of C. sativa sex and N. tabacum origin. The refractive index can be also used to characterize different species.

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

PubMed

Uversky, Vladimir N

2016-03-25

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Novel biomaterials: plasma-enabled nanostructures and functions

NASA Astrophysics Data System (ADS)

Levchenko, Igor; Keidar, Michael; Cvelbar, Uroš; Mariotti, Davide; Mai-Prochnow, Anne; Fang, Jinghua; (Ken Ostrikov, Kostya

2016-07-01

Material processing techniques utilizing low-temperature plasmas as the main process tool feature many unique capabilities for the fabrication of various nanostructured materials. As compared with the neutral-gas based techniques and methods, the plasma-based approaches offer higher levels of energy and flux controllability, often leading to higher quality of the fabricated nanomaterials and sometimes to the synthesis of the hierarchical materials with interesting properties. Among others, nanoscale biomaterials attract significant attention due to their special properties towards the biological materials (proteins, enzymes), living cells and tissues. This review briefly examines various approaches based on the use of low-temperature plasma environments to fabricate nanoscale biomaterials exhibiting high biological activity, biological inertness for drug delivery system, and other features of the biomaterials make them highly attractive. In particular, we briefly discuss the plasma-assisted fabrication of gold and silicon nanoparticles for bio-applications; carbon nanoparticles for bioimaging and cancer therapy; carbon nanotube-based platforms for enzyme production and bacteria growth control, and other applications of low-temperature plasmas in the production of biologically-active materials.

Cysteine Cathepsins in the Secretory Vesicle Produce Active Peptides: Cathepsin L Generates Peptide Neurotransmitters and Cathepsin B Produces Beta-Amyloid of Alzheimer’s Disease

PubMed Central

Hook, Vivian; Funkelstein, Lydiane; Wegrzyn, Jill; Bark, Steven; Kindy, Mark; Hook, Gregory

2011-01-01

Recent new findings indicate significant biological roles of cysteine cathepsin proteases in secretory vesicles for production of biologically active peptides. Notably, cathepsin L in secretory vesicles has been demonstrated as a key protease for proteolytic processing of proneuropeptides (and prohormones) into active neuropeptides that are released to mediate cell-cell communication in the nervous system for neurotransmission. Moreover, cathepsin B in secretory vesicles has been recently identified as a β-secretase for production of neurotoxic β-amyloid (Aβ) peptides that accumulate in Alzheimer’s disease (AD), participating as a notable factor in the severe memory loss in AD. These secretory vesicle functions of cathepsins L and B for production of biologically active peptides contrasts with the well-known role of cathepsin proteases in lysosomes for the degradation of proteins to result in their inactivation. The unique secretory vesicle proteome indicates proteins of distinct functional categories that provide the intravesicular environment for support of cysteine cathepsin function. Features of the secretory vesicle protein systems insure optimized intravesicular conditions that support the proteolytic activity of cathepsins. These new findings of recently discovered biological roles of cathepsins L and B indicate their significance in human health and disease. PMID:21925292

The Effect of Hypoxia on Mesenchymal Stem Cell Biology

PubMed Central

Ejtehadifar, Mostafa; Shamsasenjan, Karim; Movassaghpour, Aliakbar; Akbarzadehlaleh, Parvin; Dehdilani, Nima; Abbasi, Parvaneh; Molaeipour, Zahra; Saleh, Mahshid

2015-01-01

Although physiological and pathological role of hypoxia have been appreciated in mammalians for decades however the cellular biology of hypoxia more clarified in the past 20 years. Discovery of the transcription factor hypoxia-inducible factor (HIF)-1, in the 1990s opened a new window to investigate the mechanisms behind hypoxia. In different cellular contexts HIF-1 activation show variable results by impacting various aspects of cell biology such as cell cycle, apoptosis, differentiation and etc. Mesenchymal stem cells (MSC) are unique cells which take important role in tissue regeneration. They are characterized by self-renewal capacity, multilineage potential, and immunosuppressive property. Like so many kind of cells, hypoxia induces different responses in MSCs by HIF- 1 activation. The activation of this molecule changes the growth, multiplication, differentiation and gene expression profile of MSCs in their niche by a complex of signals. This article briefly discusses the most important effects of hypoxia in growth kinetics, signalling pathways, cytokine secretion profile and expression of chemokine receptors in different conditions. PMID:26236651

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins*

PubMed Central

2016-01-01

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. PMID:26851286

A zinc-dependent epitope on the molecule of thymulin, a thymic hormone.

PubMed Central

Dardenne, M; Savino, W; Berrih, S; Bach, J F

1985-01-01

Thymulin is a nonapeptide hormone produced by thymic epithelial cells. Its biological activity is strictly dependent on the presence of the metal zinc in the molecule. Antithymulin monoclonal antibodies have been produced against either the synthetic (AS1) or the natural intraepithelial (AE1) molecule. These monoclonal antibodies were screened for their abilities to inhibit the zinc-dependent biological activity of the hormone and were shown to bind to thymic epithelial cells. By using biological and immunofluorescence assays, the two antibodies were shown to recognize exclusively the zinc-coupled thymulin molecule. Other antithymulin antibodies screened by RIA or ELISA (using a zinc-deprived substrate) recognized a zinc-independent epitope on the thymulin molecule. These data indicate the existence of a zinc-specific conformation on the thymulin molecule. They are in agreement with NMR studies showing that the zinc-containing hormone has a unique structure. Images PMID:2413455

Novel and rare prenyllipids - Occurrence and biological activity.

PubMed

Szymańska, Renata; Kruk, Jerzy

2018-01-01

The data presented indicate that there is a variety of unique prenyllipids, often of very limited taxonomic distribution, whose origin, biosynthesis, metabolism and biological function deserves to be elucidated. These compounds include tocoenols, tocochromanol esters, tocochromanol acids, plastoquinones and ubiquinones. Additionally, based on the available data, it can be assumed that there are still unrecognized prenyllipids, like prenylquinols fatty acid esters of the hydroquinone ring, including prenylquinol phosphates, and others, whose biological function might be of great importance. Our knowledge of these compounds is not only important from the scientific point of view, but may also be of practical significance to medicine, pharmacy or cosmetics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Nanogel Carrier Design for Targeted Drug Delivery

PubMed Central

Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

2014-01-01

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

Nanoelectronics meets biology: from new nanoscale devices for live-cell recording to 3D innervated tissues.

PubMed

Duan, Xiaojie; Lieber, Charles M

2013-10-01

High spatiotemporal resolution interfaces between electrical sensors and biological systems, from single live cells to tissues, is crucial for many areas, including fundamental biophysical studies as well as medical monitoring and intervention. Herein, we summarize recent progress in the development and application of novel nanoscale devices for intracellular electrical recording of action potentials and the effort of merging electronic and biological systems seamlessly in three dimensions by using macroporous nanoelectronic scaffolds. The uniqueness of these nanoscale devices for minimally invasive, large-scale, high spatial resolution, and three-dimensional neural activity mapping are highlighted. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Does a prosocial-selfish distinction help explain the biological affects? Comment on Buck (1999).

PubMed

Gray, Jeremy R

2002-10-01

R. Buck (1999) argued that a conceptual distinction between prosocial and selfish motivation is necessary to understand the biological affects (consciously experienced feelings and desires having an innate neurochemical basis). However, at a biological level of analysis, a prosocial-selfish distinction is doubtful empirically and conceptually. For this reason, Buck's proposed typology of biological affects is unclear. Moreover, a prosocial-selfish distinction is not necessary to explain hemispheric differences in brain activity associated with affect. In contrast, an approach-withdrawal distinction explains some data uniquely well, although numerous exceptions imply that simple models are inadequate. To extend hemispheric models of experienced emotion, a prosocial-selfish distinction is unlikely to be explanatory, whereas an alternative account based on a distinction between verbal and nonverbal working memory may be useful.

Low concentrations of copper in drinking water increase AP-1 binding in the brain.

PubMed

Lung, Shyang; Li, Huihui; Bondy, Stephen C; Campbell, Arezoo

2015-12-01

Copper (Cu) in trace amounts is essential for biological organisms. However, dysregulation of the redox-active metal has been implicated in different neurological disorders such as Wilson's, Menkes', Alzheimer's, and Parkinson's diseases. Since many households use Cu tubing in the plumbing system, and corrosion causes the metal to leach into the drinking water, there may be adverse effects on the central nervous system connected with low-level chronic exposure. The present study demonstrates that treatment with a biologically relevant concentration of Cu for 3 months significantly increases activation of the redox-modulated transcription factor AP-1 in mouse brains. This was independent of an upstream kinase indicated in AP-1 activation. Another redox-active transcription factor, NF-κB, was not significantly modified by the Cu exposure. These results indicate that the effect of Cu on AP-1 is unique and may involve direct modulation of DNA binding. © The Author(s) 2012.

Lipids and Fatty Acids of Nudibranch Mollusks: Potential Sources of Bioactive Compounds

PubMed Central

Zhukova, Natalia V.

2014-01-01

The molecular diversity of chemical compounds found in marine animals offers a good chance for the discovery of novel bioactive compounds of unique structures and diverse biological activities. Nudibranch mollusks, which are not protected by a shell and produce chemicals for various ecological uses, including defense against predators, have attracted great interest for their lipid composition. Lipid analysis of eight nudibranch species revealed dominant phospholipids, sterols and monoalkyldiacylglycerols. Among polar lipids, 1-alkenyl-2-acyl glycerophospholipids (plasmalogens) and ceramide-aminoethyl phosphonates were found in the mollusks. The fatty acid compositions of the nudibranchs differed greatly from those of other marine gastropods and exhibited a wide diversity: very long chain fatty acids known as demospongic acids, a series of non-methylene-interrupted fatty acids, including unusual 21:2∆7,13, and an abundance of various odd and branched fatty acids typical of bacteria. Symbiotic bacteria revealed in some species of nudibranchs participate presumably in the production of some compounds serving as a chemical defense for the mollusks. The unique fatty acid composition of the nudibranchs is determined by food supply, inherent biosynthetic activities and intracellular symbiotic microorganisms. The potential of nudibranchs as a source of biologically active lipids and fatty acids is also discussed. PMID:25196731

Heterocyclic cationic gemini surfactants: a comparative overview of their synthesis, self-assembling, physicochemical, and biological properties.

PubMed

Sharma, Vishnu Dutt; Ilies, Marc A

2014-01-01

Gemini surfactants (GS) are presently receiving substantial attention due to their special self-assembling properties and unique interfacial activity. This comprehensive review is focused on positively charged heterocyclic GS, presenting their major synthetic access routes and examining the impact of structural elements on physicochemical and aggregation properties of this class of amphiphiles. Interaction of geminis surfactants with cells and their biological properties as novel transfection agents are emphasized through a detailed structure-activity relationship analysis. Throughout the review we have also presented the properties of selected ammonium GS, simple surfactants and lipid congeners, in order to emphasize the advantages conferred by using heterocyclic polar heads in GS design. © 2012 Wiley Periodicals, Inc.

Biological Weapons Attribution: A Primer

DTIC Science & Technology

2007-06-01

attacks are very difficult: (1) the nature of biological weapons, (2) the unique restrictions the international environment places on BW attribution, and...provides a basic epistemological framework for analysis for successful BW attribution, detailing the nature , methods, and limits of current BW...difficult: (1) the nature of biological weapons, (2) the unique restrictions the international environment places on BW attribution, and (3) the

Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells

PubMed Central

Feng, Weiguo; Gentles, Andrew; Nair, Ramesh V.; Huang, Min; Lin, Yuan; Lee, Cleo Y.; Cai, Shang; Scheeren, Ferenc A.; Kuo, Angera H.; Diehn, Maximilian

2014-01-01

Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about heterogeneity of metabolic properties cancer stem cells, also called tumor initiating cells (TICs). In this study we show that, analogous to some normal stem cells, breast TICs have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial biology and mitochondrial oxidative phosphorylation and metabolic analyses revealed TICs preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. Mechanistic analyses demonstrated that decreased expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation, play a critical role in promoting the pro-glycolytic phenotype of TICs. Metabolic reprogramming via forced activation of Pdh preferentially eliminates TICs both in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and demonstrate that metabolic reprogramming represents a promising strategy for targeting these cells. PMID:24497069

Recent advances in the discovery of potent and selective HDAC6 inhibitors.

PubMed

Wang, Xiu-Xiu; Wan, Ren-Zhong; Liu, Zhao-Peng

2018-01-01

Histone deacetylase HDAC6, a member of the class IIb HDAC family, is unique among HDAC enzymes in having two active catalytic domains, and has unique physiological function. In addition to the modification of histone, HDAC6 targets specific substrates including α-tubulin and HSP90, and are involved in protein trafficking and degradation, cell shape and migration. Selective HDAC6 inhibitors are an emerging class of pharmaceuticals due to the involvement of HDAC6 in different pathways related to neurodegenerative diseases, cancer, and immunology. Therefore, extensive investigations have been made in the discovery of selective HDAC6 inhibitors. Based on their different zinc binding groups (ZBGs), in this review, HDAC6 inhibitors are grouped as hydroxamic acids, a sulfur containing ZBG based derivatives and other ZBG-derived compounds, and their enzymatic inhibitory activity, selectivity and other biological activities are introduced and summarized. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status.

PubMed

Fang, Wan-Yin; Dahiya, Rajiv; Qin, Hua-Li; Mourya, Rita; Maharaj, Sandeep

2016-10-26

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs.

Natural Proline-Rich Cyclopolypeptides from Marine Organisms: Chemistry, Synthetic Methodologies and Biological Status

PubMed Central

Fang, Wan-Yin; Dahiya, Rajiv; Qin, Hua-Li; Mourya, Rita; Maharaj, Sandeep

2016-01-01

Peptides have gained increased interest as therapeutics during recent years. More than 60 peptide drugs have reached the market for the benefit of patients and several hundreds of novel therapeutic peptides are in preclinical and clinical development. The key contributor to this success is the potent and specific, yet safe, mode of action of peptides. Among the wide range of biologically-active peptides, naturally-occurring marine-derived cyclopolypeptides exhibit a broad range of unusual and potent pharmacological activities. Because of their size and complexity, proline-rich cyclic peptides (PRCPs) occupy a crucial chemical space in drug discovery that may provide useful scaffolds for modulating more challenging biological targets, such as protein-protein interactions and allosteric binding sites. Diverse pharmacological activities of natural cyclic peptides from marine sponges, tunicates and cyanobacteria have encouraged efforts to develop cyclic peptides with well-known synthetic methods, including solid-phase and solution-phase techniques of peptide synthesis. The present review highlights the natural resources, unique structural features and the most relevant biological properties of proline-rich peptides of marine-origin, focusing on the potential therapeutic role that the PRCPs may play as a promising source of new peptide-based novel drugs. PMID:27792168

Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

NASA Astrophysics Data System (ADS)

Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

2013-06-01

Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

Biogeochemical linkage between atmosphere and ocean in the eastern equatorial Pacific Ocean: Results from the EqPOS research cruise

NASA Astrophysics Data System (ADS)

Furutani, H.; Inai, Y.; Aoki, S.; Honda, H.; Omori, Y.; Tanimoto, H.; Iwata, T.; Ueda, S.; Miura, K.; Uematsu, M.

2012-12-01

Eastern equatorial Pacific Ocean is a unique oceanic region from several biogeochemical points of view. It is a remote open ocean with relatively high marine biological activity, which would result in limited influence of human activity but enhanced effect of marine natural processes on atmospheric composition. It is also characterized as high nutrient low chlorophyll (HNLC) ocean, in which availability of trace metals such as iron and zinc limits marine primary production and thus atmospheric deposition of these trace elements to the ocean surface is expected to play an important role in regulating marine primary production and defining unique microbial community. High sea surface temperature in the region generates strong vertical air convection which efficiently brings tropospheric atmospheric composition into stratosphere. In this unique eastern equatorial Pacific Ocean, EqPOS (Equatorial Pacific Ocean and Stratospheric/Tropospheric Atmospheric Study) research cruise was organized as a part of SOLAS Japan activity to understand biogeochemical ocean-atmospheric interaction in the region. Coordinated atmospheric, oceanic, and marine biological observations including sampling/characterization of thin air-sea interfacial layer (sea surface microlayer: SML) and launching large stratospheric air sampling balloons were carried out on-board R/V Hakuho Maru starting from 29 January for 39 days. Biogeochemically important trace/long-lived gases such as CO2, dimethyl sulfide (DMS), and some volatile organic carbons (VOCs) both in the atmosphere and seawater were continuously monitored and their air-sea fluxes were also observed using gradient and eddy-covariance techniques. Atmospheric gas measurement of CO2, CH4, N2O, SF6, CO, H2, Ar and isotopic composition of selected gases were further extended to stratospheric air by balloon-born sampling in addition to a vertical profiling of O3, CO2, and H2O with sounding sondes. Physical and chemical properties of marine atmospheric aerosols such as size distribution, total and cloud condensation nuclei concentrations, particle morphology, bulk and single particle chemical composition were also continuously determined to find out potential link between biogenic VOCs emitted from the ocean and aerosol composition. Biological and biogeochemical characterizations of marine microorganisms, suspended particulate matter, dissolved nutrients in seawater and SML were also conducted. In the presentation, brief overview of the research activities during the EqPOS cruise and biogeochemical linkage atmosphere and ocean via atmospheric and oceanic gaseous and particulate matter from ocean surface to stratosphere observed during the cruise and unique importance of SML would be presented.

Multidisciplinary Inquiry-Based Investigation Learning Using an Ex Ovo Chicken Culture Platform: Role of Vitamin A on Embryonic Morphogenesis

ERIC Educational Resources Information Center

Buskohl, Philip R.; Gould, Russell A.; Curran, Susan; Archer, Shivaun D.; Butcher, Jonathan T.

2012-01-01

Embryonic development offers a unique perspective on the function of many biological processes because of embryos' heightened sensitivity to environmental factors. This hands-on lesson investigates the effects of elevated vitamin A on the morphogenesis of chicken embryos. The active form of vitamin A (retinoic acid) is applied to shell-less (ex…

Biological control of the cucurbit powdery mildew pathogen Podosphaera xanthii by means of the epiphytic fungus Pseudozyma aphidis and parasitism as a mode of action.

PubMed

Gafni, Aviva; Calderon, Claudia E; Harris, Raviv; Buxdorf, Kobi; Dafa-Berger, Avis; Zeilinger-Reichert, Einat; Levy, Maggie

2015-01-01

Epiphytic yeasts, which colonize plant surfaces, may possess activity that can be harnessed to help plants defend themselves against various pathogens. Due to their unique characteristics, epiphytic yeasts belonging to the genus Pseudozyma hold great potential for use as biocontrol agents. We identified a unique, biologically active isolate of the epiphytic yeast Pseudozyma aphidis that is capable of inhibiting Botrytis cinerea via a dual mode of action, namely induced resistance and antibiosis. Here, we show that strain L12 of P. aphidis can reduce the severity of powdery mildew caused by Podosphaera xanthii on cucumber plants with an efficacy of 75%. Confocal and scanning electron microscopy analyses demonstrated P. aphidis proliferation on infected tissue and its production of long hyphae that parasitize the powdery mildew hyphae and spores as an ectoparasite. We also show that crude extract of P. aphidis metabolites can inhibit P. xanthii spore germination in planta. Our results suggest that in addition to its antibiosis as mode of action, P. aphidis may also act as an ectoparasite on P. xanthii. These results indicate that P. aphidis strain L12 has the potential to control powdery mildew.

Points of View: A Survey of Survey Courses--Are They Effective? A Unique Approach? Four Semesters of Biology Core Curriculum

ERIC Educational Resources Information Center

Batzli, Janet M.

2005-01-01

''Why four semesters? How does this track differ from the two-semester course sequence?'' These are the most common questions students have when they learn about the Biology Core Curriculum (Biocore), a unique four-semester honors biology sequence at University of Wisconsin-Madison (UW-Madison). Biocore was first taught at University of Wisconsin…

Supraglacial sulfur springs and associated biological activity in the Canadian high arctic - signs of life beneath the ice

USGS Publications Warehouse

Grasby, Stephen E.; Allen, Carlton C.; Longazo, Teresa G.; Lisle, John T.; Griffin, Dale W.; Beauchamp, Benoit

2003-01-01

Unique springs, discharging from the surface of an arctic glacier, release H2S and deposit native sulfur, gypsum, and calcite. The presence of sulfur in three oxidation states indicates a complex series of redox reactions. Physical and chemical conditions of the spring water and surrounding environment, as well as mineralogical and isotopic signatures, suggest biologically mediated reactions. Cell counts and DNA analyses confirm bacteria are present in the spring system, and a limited number of sequenced isolates suggests that complex communities of bacteria live within the glacial system.

Interfacing Neural Network Components and Nucleic Acids

PubMed Central

Lissek, Thomas

2017-01-01

Translating neural activity into nucleic acid modifications in a controlled manner harbors unique advantages for basic neurobiology and bioengineering. It would allow for a new generation of biological computers that store output in ultra-compact and long-lived DNA and enable the investigation of animal nervous systems at unprecedented scales. Furthermore, by exploiting the ability of DNA to precisely influence neuronal activity and structure, it could be possible to more effectively create cellular therapy approaches for psychiatric diseases that are currently difficult to treat. PMID:29255707

Overexpression of miR-9 in mast cells is associated with invasive behavior and spontaneous metastasis

PubMed Central

2014-01-01

Background While microRNA (miRNA) expression is known to be altered in a variety of human malignancies contributing to cancer development and progression, the potential role of miRNA dysregulation in malignant mast cell disease has not been previously explored. The purpose of this study was to investigate the potential contribution of miRNA dysregulation to the biology of canine mast cell tumors (MCTs), a well-established spontaneous model of malignant mast cell disease. Methods We evaluated the miRNA expression profiles from biologically low-grade and biologically high-grade primary canine MCTs using real-time PCR-based TaqMan Low Density miRNA Arrays and performed real-time PCR to evaluate miR-9 expression in primary canine MCTs, malignant mast cell lines, and normal bone marrow-derived mast cells (BMMCs). Mouse mast cell lines and BMMCs were transduced with empty or pre-miR-9 expressing lentiviral constructs and cell proliferation, caspase 3/7 activity, and invasion were assessed. Transcriptional profiling of cells overexpressing miR-9 was performed using Affymetrix GeneChip Mouse Gene 2.0 ST arrays and real-time PCR was performed to validate changes in mRNA expression. Results Our data demonstrate that unique miRNA expression profiles correlate with the biological behavior of primary canine MCTs and that miR-9 expression is increased in biologically high grade canine MCTs and malignant cell lines compared to biologically low grade tumors and normal canine BMMCs. In transformed mouse malignant mast cell lines expressing either wild-type (C57) or activating (P815) KIT mutations and mouse BMMCs, miR-9 overexpression significantly enhanced invasion but had no effect on cell proliferation or apoptosis. Transcriptional profiling of normal mouse BMMCs and P815 cells possessing enforced miR-9 expression demonstrated dysregulation of several genes, including upregulation of CMA1, a protease involved in activation of matrix metalloproteases and extracellular matrix remodeling. Conclusions Our findings demonstrate that unique miRNA expression profiles correlate with the biological behavior of canine MCTs. Furthermore, dysregulation of miR-9 is associated with MCT metastasis potentially through the induction of an invasive phenotype, identifying a potentially novel pathway for therapeutic intervention. PMID:24517413

An Isozyme-specific Redox Switch in Human Brain Glycogen Phosphorylase Modulates Its Allosteric Activation by AMP.

PubMed

Mathieu, Cécile; Duval, Romain; Cocaign, Angélique; Petit, Emile; Bui, Linh-Chi; Haddad, Iman; Vinh, Joelle; Etchebest, Catherine; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-11-11

Brain glycogen and its metabolism are increasingly recognized as major players in brain functions. Moreover, alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. In the brain, both muscle and brain glycogen phosphorylase isozymes regulate glycogen mobilization. However, given their distinct regulatory features, these two isozymes could confer distinct metabolic functions of glycogen in brain. Interestingly, recent proteomics studies have identified isozyme-specific reactive cysteine residues in brain glycogen phosphorylase (bGP). In this study, we show that the activity of human bGP is redox-regulated through the formation of a disulfide bond involving a highly reactive cysteine unique to the bGP isozyme. We found that this disulfide bond acts as a redox switch that precludes the allosteric activation of the enzyme by AMP without affecting its activation by phosphorylation. This unique regulatory feature of bGP sheds new light on the isoform-specific regulation of glycogen phosphorylase and glycogen metabolism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

IN VITRO AND IN VIVO ACTIVITY OF A LYMPHOCYTE AND IMMUNE COMPLEX-DEPENDENT CHEMOTACTIC FACTOR FOR EOSINOPHILS

PubMed Central

Cohen, Stanley; Ward, Peter A.

1971-01-01

When cultured in the presence of specific antigen, lymphocytes from delayed-hypersensitive guinea pigs release a number of biologically active substances into the culture medium. Such active supernatants can react with immune complexes in vitro to generate a factor which is chemotactic for eosinophils. The factor involved is unique, since previously described chemotactic factors for other cell types require for their generation either immune complexes or substances released into lymphocyte culture, but not both. In the case of the eosinophil chemotactic factor, the interaction between the substance elaborated by the lymphocytes and the immune complexes appears to be specific in that the immune complexes must contain the same antigen as that used to activate the lymphocyte cultures. Although this factor was generated in an in vitro system, it has been shown to possess in vivo as well as in vitro activity. It is therefore possible that this factor may be of biological significance in situations where eosinophils are participants in inflammatory or immunologic reactions. PMID:5099667

Chalcones: structural requirements for antioxidant, estrogenic and antiproliferative activities.

PubMed

Calliste, C A; Le Bail, J C; Trouillas, P; Pouget, C; Habrioux, G; Chulia, A J; Duroux, J L

2001-01-01

Flavonoids are largely studied for their biological properties and particularly for their scavenging and antioxidant activities. In the present study, we first evaluated the antioxidant and the estrogenic actions of chalcones, then we tested their effects on MCF-7 cell proliferation. Chalcones are unique in the flavonoids family in lacking a heterocyclic C ring. We tested substituted chalcones with different numbers and different positions of the hydroxy groups: 2'-hydroxychalcone, 4'-hydroxychalcone, 4-hydroxychalcone, 2',4-dihydroxychalcone, isoliquiritigenin, 2',4'-dihydroxychalcone, phloretin and naringenin chalcone. For the antioxidant tests we established the importance of the alpha-beta double bond and the 6'-hydroxy group. The establishment of the structure-activity relationship for the estrogenic properties showed a correlation between the antioxidant and the estrogenic properties. The importance of conformation and hydroxy group positions observed for chalcones, having antioxidant and estrogenic properties, was also observed on MCF-7 cell growth with the same structure-activity relationship. The role of electron and hydrogen transfer in the correlation between these three biological activities was discussed.

The inception and evolution of a unique masters program in cancer biology, prevention and control.

PubMed

Cousin, Carolyn; Blancato, Jan

2010-09-01

The University of the District of Columbia (UDC) and the Lombardi Comprehensive Cancer Center (LCCC), Georgetown University Medical Center established a Masters Degree Program in Cancer Biology, Prevention and Control at UDC that is jointly administered and taught by UDC and LCCC faculty. The goal of the Masters Degree Program is to educate students as master-level cancer professionals capable of conducting research and service in cancer biology, prevention, and control or to further advance the education of students to pursue doctoral studies. The Program's unique nature is reflected in its philosophy "the best cancer prevention and control researchers are those with a sound understanding of cancer biology". This program is a full-time, 2-year, 36-credit degree in which students take half of their coursework at UDC and half of their coursework at LCCC. During the second year, students are required to conduct research either at LCCC or UDC. Unlike most cancer biology programs, this unique Program emphasizes both cancer biology and cancer outreach training.

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

PubMed Central

Kuang, Zheng; Ji, Zhicheng

2018-01-01

Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

Terminator Operon Reporter: combining a transcription termination switch with reporter technology for improved gene synthesis and synthetic biology applications.

PubMed

Zampini, Massimiliano; Mur, Luis A J; Rees Stevens, Pauline; Pachebat, Justin A; Newbold, C James; Hayes, Finbarr; Kingston-Smith, Alison

2016-05-25

Synthetic biology is characterized by the development of novel and powerful DNA fabrication methods and by the application of engineering principles to biology. The current study describes Terminator Operon Reporter (TOR), a new gene assembly technology based on the conditional activation of a reporter gene in response to sequence errors occurring at the assembly stage of the synthetic element. These errors are monitored by a transcription terminator that is placed between the synthetic gene and reporter gene. Switching of this terminator between active and inactive states dictates the transcription status of the downstream reporter gene to provide a rapid and facile readout of the accuracy of synthetic assembly. Designed specifically and uniquely for the synthesis of protein coding genes in bacteria, TOR allows the rapid and cost-effective fabrication of synthetic constructs by employing oligonucleotides at the most basic purification level (desalted) and without the need for costly and time-consuming post-synthesis correction methods. Thus, TOR streamlines gene assembly approaches, which are central to the future development of synthetic biology.

Hard tissue regeneration using bone substitutes: an update on innovations in materials

PubMed Central

Sarkar, Swapan Kumar

2015-01-01

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues. PMID:25995658

Hard tissue regeneration using bone substitutes: an update on innovations in materials.

PubMed

Sarkar, Swapan Kumar; Lee, Byong Taek

2015-05-01

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

Discovery of chitin in skeletons of non-verongiid Red Sea demosponges.

PubMed

Ehrlich, Hermann; Shaala, Lamiaa A; Youssef, Diaa T A; Żółtowska-Aksamitowska, Sonia; Tsurkan, Mikhail; Galli, Roberta; Meissner, Heike; Wysokowski, Marcin; Petrenko, Iaroslav; Tabachnick, Konstantin R; Ivanenko, Viatcheslav N; Bechmann, Nicole; Joseph, Yvonne; Jesionowski, Teofil

2018-01-01

Marine demosponges (Porifera: Demospongiae) are recognized as first metazoans which have developed over millions of years of evolution effective survival strategies based on unique metabolic pathways to produce both biologically active secondary metabolites and biopolymer-based stiff skeletons with 3D architecture. Up to date, among marine demosponges, only representatives of the Verongiida order have been known to synthetize biologically active substances as well as skeletons made of structural polysaccharide chitin. This work, to our knowledge, demonstrates for the first time that chitin is an important structural component within skeletons of non-verongiid demosponges Acarnus wolffgangi and Echinoclathria gibbosa collected in the Red Sea. Calcofluor white staining, FTIR and Raman analysis, ESI-MS, SEM, and fluorescence microscopy as well as a chitinase digestion assay were applied in order to confirm, with strong evidence, the finding of α-chitin in the skeleton of both species. We suggest that, the finding of chitin within these representatives of Poecilosclerida order is a promising step in the evaluation of these sponges as novel renewable sources for both biologically active metabolites and chitin, which are of prospective application for pharmacology and biomedicine.

Synthesis of enantiopure 2-carba-cyclic phosphatidic acid and effects of its chirality on biological functions.

PubMed

Nozaki, Emi; Gotoh, Mari; Hotta, Harumi; Hanazawa, Shuwa; Kobayashi, Susumu; Murakami-Murofushi, Kimiko

2011-04-01

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator, which has a quite unique cyclic phosphate ring at sn-2 and sn-3 positions of the glycerol backbone. We have designed and chemically synthesized several metabolically stabilized derivatives of cPA. 2-Carba-cPA (2ccPA) is one of the synthesized compounds in which the phosphate oxygen was replaced with a methylene group at the sn-2 position, and it showed much more potent biological activities than natural cPA. Here, we developed a new method of 2ccPA enantiomeric synthesis. And we examined the effects of 2ccPA enantiomers on autotaxin (ATX) activity, cancer cell invasion and nociceptive reflex. As well as racemic-2ccPA, both enantiomers showed inhibitory effects on ATX activity, cancer cell invasion and nociceptive reflex. As their effects were not significantly different from each other, the chirality of 2ccPA may not be critical for these biological functions of 2ccPA. Copyright © 2010 Elsevier B.V. All rights reserved.

In vitro interactions between splenocytes and dansylamide dye-embedded nanoparticles detected by flow cytometry

PubMed Central

Nyland, Jennifer F.; Bai, Jennifer J. K.; Katz, Howard E.; Silbergeld, Ellen K.

2009-01-01

Engineered nanoparticles (NPs) possess a range of biological activity. In vitro methods for assessing toxicity and efficacy would be enhanced by simultaneous quantitative information on the behavior of NPs in culture systems and signals of cell response. We have developed a method for visualizing NPs within cells using standard flow cytometric techniques and uniquely designed spherical siloxane NPs with an embedded (covalently bound) dansylamide dye. This method allowed NP visualization without obscuring detection of relevant biomarkers of cell subtype, activation state, and other events relevant to assessing bioactivity. We determined that NPs penetrated cells and induced a range of biological signals consistent with activation and costimulation. These results indicate that NPs may affect cell function at concentrations below those inducing cytotoxicity or apoptosis and demonstrate a novel method to image both localization of NPs and cell-level effects. PMID:19523425

Human Uterine Cervical Stromal Stem Cells (hUCESCs): Why and How they Exert their Antitumor Activity

PubMed Central

SCHNEIDER, JOSÉ; EIRÓ, NOEMÍ; PÉREZ-FERNÁNDEZ, ROMÁN; MARTÍNEZ-ORDÓÑEZ, ANXO; VIZOSO, FRANCISCO

2016-01-01

Our research team has recently isolated and characterized a new stromal stem cell line (hUCESCs) obtained from cytological smears, as routinely performed for cervical cancer screening. We have, furthermore, described that both hUCESCs directly, as well as the secretome contained in the conditioned medium used for growing them (hUCESCs-CM) have potent antitumoral, anti-inflammatory, antibiotic, antimycotic and re-epitheliasation-enhancing properties. The scientific explanation our team proposes for these pleiotropic effects are directly related to the site of origin of hUCESCs, the human cervical transition zone, which has unique features that biologically justify the different actions of hUCESCs and hUCESCs-CM. We, herein, expose our working theory for the biological activity of hUCESCs and hUCESCs-CM. PMID:27566652

Photo-damage protective effect of two facial products, containing a unique complex of Dead Sea minerals and Himalayan actives.

PubMed

Wineman, Eitan; Portugal-Cohen, Meital; Soroka, Yoram; Cohen, Dror; Schlippe, Gerrit; Voss, Werner; Brenner, Sarah; Milner, Yoram; Hai, Noam; Ma'or, Zeevi

2012-09-01

Skin appearance is badly affected when exposed to solar UV rays, which encourage physiological and structural cutaneous alterations that eventually lead to skin photo-damage. To test the capability of two facial preparations, extreme day cream (EXD) and extreme night treatment (EXN), containing a unique complex of Dead Sea water and three Himalayan extracts, to antagonize biological effects induced by photo-damage. Pieces of organ cultures of human skin were used as a model to assess the biological effects of UVB irradiation and the protective effect of topical application of two Extreme preparations. Skin pieces were analyzed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, and for cytokine secretion by solid phase ELISA. Human subjects were tested to evaluate the effect of Extreme preparations on skin wrinkle depth using PRIMOS and skin hydration by a corneometer. UVB irradiation induced cell apoptosis in the epidermis of skin organ cultures and increased their pro-inflammatory cytokine, tumor necrosis α (TNFα) secretion. Topical applications of both preparations significantly attenuated all these effects. Furthermore, in human subjects, a reduction in wrinkle depth and an elevation in the intense skin moisture were observed. The observations clearly show that EXD and EXN preparations have protective anti-apoptotic and anti-inflammatory properties that can attenuate biological effects of skin photo-damage. Topical application of the preparations improves skin appearance by reducing its wrinkles depth and increasing its moisturizing impact. © 2012 Wiley Periodicals, Inc.

Paradoxical roles of dual oxidases in cancer biology.

PubMed

Little, Andrew C; Sulovari, Arvis; Danyal, Karamatullah; Heppner, David E; Seward, David J; van der Vliet, Albert

2017-09-01

Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities. Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-center feasibility study evaluating recruitment, variability in risk factors and biomarkers for a diet and cancer cohort in India

PubMed Central

2011-01-01

Background India's population exhibits diverse dietary habits and chronic disease patterns. Nutritional epidemiologic studies in India are primarily of cross-sectional or case-control design and subject to biases, including differential recall of past diet. The aim of this feasibility study was to evaluate whether a diet-focused cohort study of cancer could be established in India, providing insight into potentially unique diet and lifestyle exposures. Methods Field staff contacted 7,064 households within three regions of India (New Delhi, Mumbai, and Trivandrum) and found 4,671 eligible adults aged 35-69 years. Participants completed interviewer-administered questionnaires (demographic, diet history, physical activity, medical/reproductive history, tobacco/alcohol use, and occupational history), and staff collected biological samples (blood, urine, and toenail clippings), anthropometric measurements (weight, standing and sitting height; waist, hip, and thigh circumference; triceps, sub-scapula and supra-patella skin fold), and blood pressure measurements. Results Eighty-eight percent of eligible subjects completed all questionnaires and 67% provided biological samples. Unique protein sources by region were fish in Trivandrum, dairy in New Delhi, and pulses (legumes) in Mumbai. Consumption of meat, alcohol, fast food, and soft drinks was scarce in all three regions. A large percentage of the participants were centrally obese and had elevated blood glucose levels. New Delhi participants were also the least physically active and had elevated lipids levels, suggesting a high prevalence of metabolic syndrome. Conclusions A high percentage of participants complied with study procedures including biological sample collection. Epidemiologic expertise and sufficient infrastructure exists at these three sites in India to successfully carry out a modest sized population-based study; however, we identified some potential problems in conducting a cohort study, such as limited number of facilities to handle biological samples. PMID:21619649

Mindfulness: Reconnecting the Body and Mind in Geriatric Medicine and Gerontology

PubMed Central

Rejeski, W. Jack

2008-01-01

Derived from Buddhism, mindfulness is a unique approach for understanding human suffering and happiness that has attracted rapidly growing interest among health care professionals. In this article I describe current thinking about the concept of mindfulness and elaborate on why and how mindfulness-based interventions have potential within the context of geriatric medicine and gerontology. Upon reviewing definitions and models of the concept, I give attention to the unique role that the body plays in cultivating mindfulness and the advantages that this focus has for older adults because they have aging biological systems and may experience chronic disease, pain, and disability. In the final section I discuss why mindfulness may be particularly useful in promoting physical activity among older adults and how physical activity may be used as a vehicle to promote mindfulness. PMID:18483425

DOE Office of Scientific and Technical Information (OSTI.GOV)

McChesney, J.D.

The chemical substances utilized in consumer products, and for pharmaceutical and agricultural uses are generally referred to as specialty chemicals. These may be flavor or fragrance substances, intermediates for synthesis of drugs or agrochemicals or the drugs or agrochemicals themselves, insecticides or insect pheromones or antifeedants, plant growth regulators, etc. These are in contrast to chemicals which are utilized in large quantities for fuels or preparation of plastics, lubricants, etc., which are usually referred to as industrial chemicals. The specific utilization of specialty chemicals is associated with a specific important physiochemical or biological property. They may possess unique properties asmore » lubricants or waxes or have a very desirable biological activity such as a drug, agrochemical or perfume ingredient. These unique properties convey significant economic value to the specific specialty chemical. The economic commercial production of specialty chemicals commonly requires the isolation of a precursor or the specialty chemical itself from a natural source. The discovery, development and commercialization of specialty chemicals is presented and reviewed. The economic and sustainable production of specialty chemicals is discussed.« less

Building an Undergraduate STEM Team Using Team-Based Learning Leading to the Production of a Storyboard Appropriate for Elementary Students

ERIC Educational Resources Information Center

Cutright, Teresa J.; Evans, Edward; Brantner, Justin S.

2014-01-01

A unique undergraduate team that spans five different engineering disciplines, chemistry, biology, and mathematics was formed. The team was formed to promote cross-disciplinary learning, to improve retention, and to prepare the students for the kind of problems they will face in their careers. This paper describes the variety of activities used…

Industrial activated sludge exhibit unique bacterial community composition at high taxonomic ranks.

PubMed

Ibarbalz, Federico M; Figuerola, Eva L M; Erijman, Leonardo

2013-07-01

Biological degradation of domestic and industrial wastewater by activated sludge depends on a common process of separation of the diverse self-assembled and self-sustained microbial flocs from the treated wastewater. Previous surveys of bacterial communities indicated the presence of a common core of bacterial phyla in municipal activated sludge, an observation consistent with the concept of ecological coherence of high taxonomic ranks. The aim of this work was to test whether this critical feature brings about a common pattern of abundance distribution of high bacterial taxa in industrial and domestic activated sludge, and to relate the bacterial community structure of industrial activated sludge with relevant operational parameters. We have applied 454 pyrosequencing of 16S rRNA genes to evaluate bacterial communities in full-scale biological wastewater treatment plants sampled at different times, including seven systems treating wastewater from different industries and one plant that treats domestic wastewater, and compared our datasets with the data from municipal wastewater treatment plants obtained by three different laboratories. We observed that each industrial activated sludge system exhibited a unique bacterial community composition, which is clearly distinct from the common profile of bacterial phyla or classes observed in municipal plants. The influence of process parameters on the bacterial community structure was evaluated using constrained analysis of principal coordinates (CAP). Part of the differences in the bacterial community structure between industrial wastewater treatment systems were explained by dissolved oxygen and pH. Despite the ecological relevance of floc formation for the assembly of bacterial communities in activated sludge, the wastewater characteristics are likely to be the major determinant that drives bacterial composition at high taxonomic ranks. Copyright © 2013 Elsevier Ltd. All rights reserved.

Porous NiTi for bone implants: a review.

PubMed

Bansiddhi, A; Sargeant, T D; Stupp, S I; Dunand, D C

2008-07-01

NiTi foams are unique among biocompatible porous metals because of their high recovery strain (due to the shape-memory or superelastic effects) and their low stiffness facilitating integration with bone structures. To optimize NiTi foams for bone implant applications, two key areas are under active study: synthesis of foams with optimal architectures, microstructure and mechanical properties; and tailoring of biological interactions through modifications of pore surfaces. This article reviews recent research on NiTi foams for bone replacement, focusing on three specific topics: (i) surface modifications designed to create bio-inert porous NiTi surfaces with low Ni release and corrosion, as well as bioactive surfaces to enhance and accelerate biological activity; (ii) in vitro and in vivo biocompatibility studies to confirm the long-term safety of porous NiTi implants; and (iii) biological evaluations for specific applications, such as in intervertebral fusion devices and bone tissue scaffolds. Possible future directions for bio-performance and processing studies are discussed that could lead to optimized porous NiTi implants.

Porous NiTi for bone implants: A review

PubMed Central

Bansiddhi, A.; Sargeant, T.D.; Stupp, S.I.; Dunand, D.C.

2011-01-01

NiTi foams are unique among biocompatible porous metals because of their high recovery strain (due to the shape-memory or superelastic effects) and their low stiffness facilitating integration with bone structures. To optimize NiTi foams for bone implant applications, two key areas are under active study: synthesis of foams with optimal architectures, microstructure and mechanical properties; and tailoring of biological interactions through modifications of pore surfaces. This article reviews recent research on NiTi foams for bone replacement, focusing on three specific topics: (i) surface modifications designed to create bio-inert porous NiTi surfaces with low Ni release and corrosion, as well as bioactive surfaces to enhance and accelerate biological activity; (ii) In vitro and in vivo biocompatibility studies to confirm the long-term safety of porous NiTi implants; and (iii) biological evaluations for specific applications, such as in intervertebral fusion devices and bone tissue scaffolds. Possible future directions for bio-performance and processing studies are discussed that could lead to optimized porous NiTi implants. PMID:18348912

Marine natural product peptides with therapeutic potential: Chemistry, biosynthesis, and pharmacology.

PubMed

Gogineni, Vedanjali; Hamann, Mark T

2018-01-01

The oceans are a uniquely rich source of bioactive metabolites, of which sponges have been shown to be among the most prolific producers of diverse bioactive secondary metabolites with valuable therapeutic potential. Much attention has been focused on marine bioactive peptides due to their novel chemistry and diverse biological properties. As summarized in this review, marine peptides are known to exhibit various biological activities such as antiviral, anti-proliferative, antioxidant, anti-coagulant, anti-hypertensive, anti-cancer, antidiabetic, antiobesity, and calcium-binding activities. This review focuses on the chemistry and biology of peptides isolated from sponges, bacteria, cyanobacteria, fungi, ascidians, and other marine sources. The role of marine invertebrate microbiomes in natural products biosynthesis is discussed in this review along with the biosynthesis of modified peptides from different marine sources. The status of peptides in various phases of clinical trials is presented, as well as the development of modified peptides including optimization of PK and bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

The functional role of xylem parenchyma cells and aquaporins during recovery from severe water stress.

PubMed

Secchi, Francesca; Pagliarani, Chiara; Zwieniecki, Maciej A

2017-06-01

Xylem parenchyma cells [vessel associated cells (VACs)] constitute a significant fraction of the xylem in woody plants. These cells are often closely connected with xylem vessels or tracheids via simple pores (remnants of plasmodesmata fields). The close contact and biological activity of VACs during times of severe water stress and recovery from stress suggest that they are involved in the maintenance of xylem transport capacity and responsible for the restoration of vessel/tracheid functionality following embolism events. As recovery from embolism requires the transport of water across xylem parenchyma cell membranes, an understanding of stem-specific aquaporin expression patterns, localization and activity is a crucial part of any biological model dealing with embolism recovery processes in woody plants. In this review, we provide a short overview of xylem parenchyma cell biology with a special focus on aquaporins. In particular we address their distributions and activity during the development of drought stress, during the formation of embolism and the subsequent recovery from stress that may result in refilling. Complemented by the current biological model of parenchyma cell function during recovery from stress, this overview highlights recent breakthroughs on the unique ability of long-lived perennial plants to undergo cycles of embolism-recovery related to drought/rewetting or freeze/thaw events. © 2016 John Wiley & Sons Ltd.

Exploring 'new' bioactivities of polymers at the nano-bio interface.

PubMed

Wang, Chunming; Dong, Lei

2015-01-01

A biological system is essentially an elegant assembly of polymeric nanostructures. The polymers in the body, biomacromolecules, are both building blocks and versatile messengers. We propose that non-biologically derived polymers can be potential therapeutic candidates with unique advantages. Emerging findings about polycations, polysaccharides, immobilised multivalent ligands, and biomolecular coronas provide evidence that polymers are activated at the nano-bio interface, while emphasising the current theoretical and practical challenges. Our increasing understanding of the nano-bio interface and evolving approaches to establish the therapeutic potential of polymers enable the development of polymer drugs with high specificities for broad applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Eco-friendly approach for nanoparticles synthesis and mechanism behind antibacterial activity of silver and anticancer activity of gold nanoparticles.

PubMed

Patil, Maheshkumar Prakash; Kim, Gun-Do

2017-01-01

This review covers general information about the eco-friendly process for the synthesis of silver nanoparticles (AgNP) and gold nanoparticles (AuNP) and focuses on mechanism of the antibacterial activity of AgNPs and the anticancer activity of AuNPs. Biomolecules in the plant extract are involved in reduction of metal ions to nanoparticle in a one-step and eco-friendly synthesis process. Natural plant extracts contain wide range of metabolites including carbohydrates, alkaloids, terpenoids, phenolic compounds, and enzymes. A variety of plant species and plant parts have been successfully extracted and utilized for AgNP and AuNP syntheses. Green-synthesized nanoparticles eliminate the need for a stabilizing and capping agent and show shape and size-dependent biological activities. Here, we describe some of the plant extracts involved in nanoparticle synthesis, characterization methods, and biological applications. Nanoparticles are important in the field of pharmaceuticals for their strong antibacterial and anticancer activity. Considering the importance and uniqueness of this concept, the synthesis, characterization, and application of AgNPs and AuNPs are discussed in this review.

Omnipresence of the polyproline II helix in fibrous and globular proteins.

PubMed

Esipova, Natalia G; Tumanyan, Vladimir G

2017-02-01

Left-handed helical conformation of a polypeptide chain (PPII) is the third type of the protein backbone structure. This conformation universally exists in fibrous, globular proteins, and biologically active peptides. It has unique physical and chemical properties determining a wide range of biological functions, from the protein folding to the tissue differentiation. New examples of the structure have been appearing in spite of difficulties in their detection and investigation. The annotation and prediction of the PPII was also a challenging task. Recently, many PPII motifs with new and/or unexpected functions are being accumulated in databases. In this review we describe the major structural and dynamic forms of PPII, the diversity of its functions, and the role in different biological processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic biology of cyanobacteria: unique challenges and opportunities

PubMed Central

Berla, Bertram M.; Saha, Rajib; Immethun, Cheryl M.; Maranas, Costas D.; Moon, Tae Seok; Pakrasi, Himadri B.

2013-01-01

Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria's potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as “chassis” strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a “green E. coli.” In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints. PMID:24009604

Normalization of TAM post-receptor signaling reveals a cell invasive signature for Axl tyrosine kinase.

PubMed

Kimani, Stanley G; Kumar, Sushil; Davra, Viralkumar; Chang, Yun-Juan; Kasikara, Canan; Geng, Ke; Tsou, Wen-I; Wang, Shenyan; Hoque, Mainul; Boháč, Andrej; Lewis-Antes, Anita; De Lorenzo, Mariana S; Kotenko, Sergei V; Birge, Raymond B

2016-09-06

Tyro3, Axl, and Mertk (TAMs) are a family of three conserved receptor tyrosine kinases that have pleiotropic roles in innate immunity and homeostasis and when overexpressed in cancer cells can drive tumorigenesis. In the present study, we engineered EGFR/TAM chimeric receptors (EGFR/Tyro3, EGFR/Axl, and EGF/Mertk) with the goals to interrogate post-receptor functions of TAMs, and query whether TAMs have unique or overlapping post-receptor activation profiles. Stable expression of EGFR/TAMs in EGFR-deficient CHO cells afforded robust EGF inducible TAM receptor phosphorylation and activation of downstream signaling. Using a series of unbiased screening approaches, that include kinome-view analysis, phosphor-arrays, RNAseq/GSEA analysis, as well as cell biological and in vivo readouts, we provide evidence that each TAM has unique post-receptor signaling platforms and identify an intrinsic role for Axl that impinges on cell motility and invasion compared to Tyro3 and Mertk. These studies demonstrate that TAM show unique post-receptor signatures that impinge on distinct gene expression profiles and tumorigenic outcomes.

Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

DTIC Science & Technology

2004-08-01

established MTCIL tumor rolls retain this unique biologic feature. -ll suspeniionsw from sth moat vsital porn MTP ntutur arnd injected we inoutlated...rather than linear or continuous process. This biologic growth pattern is not unique nor unprecedented. Growth studies in children using serial height

Characterization, Preparation, and Purification of Marine Bioactive Peptides

PubMed Central

Wang, Xueqin; Yu, Huahua; Xing, Ronge

2017-01-01

Marine bioactive peptides, as a source of unique bioactive compounds, are the focus of current research. They exert various biological roles, some of the most crucial of which are antioxidant activity, antimicrobial activity, anticancer activity, antihypertensive activity, anti-inflammatory activity, and so forth, and specific characteristics of the bioactivities are described. This review also describes various manufacturing techniques for marine bioactive peptides using organic synthesis, microwave assisted extraction, chemical hydrolysis, and enzymes hydrolysis. Finally, purification of marine bioactive peptides is described, including gel or size exclusion chromatography, ion-exchange column chromatography, and reversed-phase high-performance liquid chromatography, which are aimed at finding a fast, simple, and effective method to obtain the target peptides. PMID:28761878

Cell-based composite materials with programmed structures and functions

DOEpatents

None

2016-03-01

The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

Cell-based composite materials with programmed structures and functions

DOEpatents

Kaehr, Bryan J.; Brinker, C. Jeffrey; Townson, Jason L.

2018-05-15

The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

Marine actinobacteria: an important source of bioactive natural products.

PubMed

Manivasagan, Panchanathan; Kang, Kyong-Hwa; Sivakumar, Kannan; Li-Chan, Eunice C Y; Oh, Hyun-Myung; Kim, Se-Kwon

2014-07-01

Marine environment is largely an untapped source for deriving actinobacteria, having potential to produce novel, bioactive natural products. Actinobacteria are the prolific producers of pharmaceutically active secondary metabolites, accounting for about 70% of the naturally derived compounds that are currently in clinical use. Among the various actinobacterial genera, Actinomadura, Actinoplanes, Amycolatopsis, Marinispora, Micromonospora, Nocardiopsis, Saccharopolyspora, Salinispora, Streptomyces and Verrucosispora are the major potential producers of commercially important bioactive natural products. In this respect, Streptomyces ranks first with a large number of bioactive natural products. Marine actinobacteria are unique enhancing quite different biological properties including antimicrobial, anticancer, antiviral, insecticidal and enzyme inhibitory activities. They have attracted global in the last ten years for their ability to produce pharmaceutically active compounds. In this review, we have focused attention on the bioactive natural products isolated from marine actinobacteria, possessing unique chemical structures that may form the basis for synthesis of novel drugs that could be used to combat resistant pathogenic microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Tyrosine Kinase Signaling in Clear Cell and Papillary Renal Cell Carcinoma Revealed by Mass Spectrometry-Based Phosphotyrosine Proteomics

PubMed Central

Haake, Scott M.; Li, Jiannong; Bai, Yun; Kinose, Fumi; Fang, Bin; Welsh, Eric; Zent, Roy; Dhillon, Jasreman; Pow-Sang, Julio; Chen, Yian Ann; Koomen, John; Rathmell, W. Kimryn; Fishman, Mayer; Haura, Eric B.

2016-01-01

Purpose Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes. Experimental Design Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. In order to describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry-based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed. Results Among the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, while DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets. Conclusions Tyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology amongst kidney cancer subtypes. PMID:27220961

Life Sciences Accomplishments 1994

NASA Technical Reports Server (NTRS)

Burnell, Mary Lou (Editor)

1993-01-01

The NASA Life and Biomedical Sciences and Applications Division (LBSAD) serves the Nation's life sciences community by managing all aspects of U.S. space-related life sciences research and technology development. The activities of the Division are integral components of the Nation's overall biological sciences and biomedical research efforts. However, NASA's life sciences activities are unique, in that space flight affords the opportunity to study and characterize basic biological mechanisms in ways not possible on Earth. By utilizing access to space as a research tool, NASA advances fundamental knowledge of the way in which weightlessness, radiation, and other aspects of the space-flight environment interact with biological processes. This knowledge is applied to procedures and technologies that enable humans to live and work in and explore space and contributes to the health and well-being of people on Earth. The activities of the Division are guided by the following three goals: Goal 1) Use microgravity and other unique aspects of the space environment to enhance our understanding of fundamental biological processes. Goal 2) Develop the scientific and technological foundations for supporting exploration by enabling productive human presence in space for extended periods. Goal 3) Apply our unique mission personnel, facilities, and technology to improve education, the quality of life on Earth, and U.S. competitiveness. The Division pursues these goals with integrated ground and flight programs involving the participation of NASA field centers, industry, and universities, as well as interactions with other national agencies and NASA's international partners. The published work of Division-sponsored researchers is a record of completed research in pursuit of these goals. During 1993, the LBSAD instituted significant changes in its experiment solicitation and peer review processes. For the first time, a NASA Research Announcement (NRA) was released requesting proposals for ground-based and flight research for all programs. Areas of particular interest to NASA were defined Proposals due April 29, 1994, will be peer reviewed - externally for scientific merit. This annual NRA process is now the mechanism for recruiting both extramural and intramural investigations. As an overview of LBSAD activities in 1993, this accomplishments document covers each of the major organizational components of the Division and the accomplishments of each. The second section is a review of the Space Life Sciences Research programs Space Biology, Space Physiology and Countermeasures, Radiation Health, Environmental Health, Space Human Factors, Advanced Life Support, and Global Monitoring and Disease Prediction, The third section, Research in Space Flight, describes the substantial contributions of the Spacelab Life Sciences 2 (SLS-2) mission to life sciences research and the significant contributions of the other missions flown in 1993, along with plans for future missions. The Division has greatly expanded and given high priority to its Education and Outreach Programs, which are presented in the fourth section. The fifth and final section, Partners for Space, shows the Divisions Cooperative efforts with other national and international agencies to achieve common goals, along with the accomplishments of joint research and analysis programs.

Biological control of the cucurbit powdery mildew pathogen Podosphaera xanthii by means of the epiphytic fungus Pseudozyma aphidis and parasitism as a mode of action

PubMed Central

Gafni, Aviva; Calderon, Claudia E.; Harris, Raviv; Buxdorf, Kobi; Dafa-Berger, Avis; Zeilinger-Reichert, Einat; Levy, Maggie

2015-01-01

Epiphytic yeasts, which colonize plant surfaces, may possess activity that can be harnessed to help plants defend themselves against various pathogens. Due to their unique characteristics, epiphytic yeasts belonging to the genus Pseudozyma hold great potential for use as biocontrol agents. We identified a unique, biologically active isolate of the epiphytic yeast Pseudozyma aphidis that is capable of inhibiting Botrytis cinerea via a dual mode of action, namely induced resistance and antibiosis. Here, we show that strain L12 of P. aphidis can reduce the severity of powdery mildew caused by Podosphaera xanthii on cucumber plants with an efficacy of 75%. Confocal and scanning electron microscopy analyses demonstrated P. aphidis proliferation on infected tissue and its production of long hyphae that parasitize the powdery mildew hyphae and spores as an ectoparasite. We also show that crude extract of P. aphidis metabolites can inhibit P. xanthii spore germination in planta. Our results suggest that in addition to its antibiosis as mode of action, P. aphidis may also act as an ectoparasite on P. xanthii. These results indicate that P. aphidis strain L12 has the potential to control powdery mildew. PMID:25814995

Drugs as habitable planets in the space of dark chemical matter.

PubMed

Siramshetty, Vishal B; Preissner, Robert

2018-03-01

A recent study demonstrated antifungal activity of dark chemical matter (DCM) compounds that were otherwise inactive in more than 100 HTS assays. These compounds were proposed to possess unique activity and 'clean' safety profiles. Here, we present an outlook of the promiscuity and safety of these compounds by retrospectively comparing their chemical and biological spaces with those of drugs. Significant amounts of marketed drugs (16%), withdrawn drugs (16.5%) and natural compounds (3.5%) share structural identity with DCM. Compound promiscuity assessment indicates that dark matter compounds could potentially interact with multiple biological targets. Further, thousands of DCM compounds showed presence of frequent-hitting pan-assay interference compound (PAINS) substructures. In light of these observations, filtering these compounds from screening libraries can be an irrevocable loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Naegleria genome: a free-living microbial eukaryote lends unique insights into core eukaryotic cell biology

PubMed Central

Fritz-Laylin, Lillian K.; Ginger, Michael L.; Walsh, Charles; Dawson, Scott C.; Fulton, Chandler

2016-01-01

Naegleria gruberi, a free-living protist, has long been treasured as a model for basal body and flagellar assembly due to its ability to differentiate from crawling amoebae into swimming flagellates. The full genome sequence of Naegleria gruberi has recently been used to estimate gene families ancestral to all eukaryotes and to identify novel aspects of Naegleria biology, including likely facultative anaerobic metabolism, extensive signaling cascades, and evidence for sexuality. Distinctive features of the Naegleria genome and nuclear biology provide unique perspectives for comparative cell biology, including cell division, RNA processing and nucleolar assembly. We highlight here exciting new and novel aspects of Naegleria biology identified through genomic analysis. PMID:21392573

IFN-λ: A New Inducer of Local Immunity against Cancer and Infections.

PubMed

Lasfar, Ahmed; Zloza, Andrew; de la Torre, Andrew; Cohen-Solal, Karine A

2016-01-01

IFN-λ is the newly established type III IFN with unique immunomodulatory functions. In contrast to the IFN-α/β family and to some extent IFN-γ, IFN-λ is apparently acting in specific areas of the body to activate resident immune cells and induces a local immunity, instrumental in preventing particular infections and also keeping transformed cells under control. Mucosal areas of lung and gastrointestinal tracts are now under scrutiny to elucidate the immune mechanisms triggered by IFN-λ and leading to viral protection. New evidence also indicates the crucial role of IFN-λ in promoting innate immunity in solid cancer models. Based on its unique biological activities among the IFN system, new immunotherapeutic approaches are now emerging for the treatment of cancer, infection, and autoimmune diseases. In the present review, we highlight the recent advances of IFN-λ immunomodulatory functions. We also discuss the perspectives of IFN-λ as a therapeutic agent.

Vibrational spectroscopy for imaging single microbial cells in complex biological samples

DOE PAGES

Harrison, Jesse P.; Berry, David

2017-04-13

Here, vibrational spectroscopy is increasingly used for the rapid and non-destructive imaging of environmental and medical samples. Both Raman and Fourier-transform infrared (FT-IR) imaging have been applied to obtain detailed information on the chemical composition of biological materials, ranging from single microbial cells to tissues. Due to its compatibility with methods such as stable isotope labeling for the monitoring of cellular activities, vibrational spectroscopy also holds considerable power as a tool in microbial ecology. Chemical imaging of undisturbed biological systems (such as live cells in their native habitats) presents unique challenges due to the physical and chemical complexity of themore » samples, potential for spectral interference, and frequent need for real-time measurements. This Mini Review provides a critical synthesis of recent applications of Raman and FT-IR spectroscopy for characterizing complex biological samples, with a focus on developments in single-cell imaging. We also discuss how new spectroscopic methods could be used to overcome current limitations of singlecell analyses. Given the inherent complementarity of Raman and FT-IR spectroscopic methods, we discuss how combining these approaches could enable us to obtain new insights into biological activities either in situ or under conditions that simulate selected properties of the natural environment.« less

Vibrational spectroscopy for imaging single microbial cells in complex biological samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harrison, Jesse P.; Berry, David

Here, vibrational spectroscopy is increasingly used for the rapid and non-destructive imaging of environmental and medical samples. Both Raman and Fourier-transform infrared (FT-IR) imaging have been applied to obtain detailed information on the chemical composition of biological materials, ranging from single microbial cells to tissues. Due to its compatibility with methods such as stable isotope labeling for the monitoring of cellular activities, vibrational spectroscopy also holds considerable power as a tool in microbial ecology. Chemical imaging of undisturbed biological systems (such as live cells in their native habitats) presents unique challenges due to the physical and chemical complexity of themore » samples, potential for spectral interference, and frequent need for real-time measurements. This Mini Review provides a critical synthesis of recent applications of Raman and FT-IR spectroscopy for characterizing complex biological samples, with a focus on developments in single-cell imaging. We also discuss how new spectroscopic methods could be used to overcome current limitations of singlecell analyses. Given the inherent complementarity of Raman and FT-IR spectroscopic methods, we discuss how combining these approaches could enable us to obtain new insights into biological activities either in situ or under conditions that simulate selected properties of the natural environment.« less

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

PubMed

Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

2018-01-09

Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bivalent Carbohydrate Binding Is Required for Biological Activity of Clitocybe nebularis Lectin (CNL), the N,N′-Diacetyllactosediamine (GalNAcβ1–4GlcNAc, LacdiNAc)-specific Lectin from Basidiomycete C. nebularis*

PubMed Central

Pohleven, Jure; Renko, Miha; Magister, Špela; Smith, David F.; Künzler, Markus; Štrukelj, Borut; Turk, Dušan; Kos, Janko; Sabotič, Jerica

2012-01-01

Lectins are carbohydrate-binding proteins that exert their biological activity by binding to specific cell glycoreceptors. We have expressed CNL, a ricin B-like lectin from the basidiomycete Clitocybe nebularis in Escherichia coli. The recombinant lectin, rCNL, agglutinates human blood group A erythrocytes and is specific for the unique glycan N,N′-diacetyllactosediamine (GalNAcβ1–4GlcNAc, LacdiNAc) as demonstrated by glycan microarray analysis. We here describe the crystal structures of rCNL in complex with lactose and LacdiNAc, defining its interactions with the sugars. CNL is a homodimeric lectin, each of whose monomers consist of a single ricin B lectin domain with its β-trefoil fold and one carbohydrate-binding site. To study the mode of CNL action, a nonsugar-binding mutant and nondimerizing monovalent CNL mutants that retain carbohydrate-binding activity were prepared. rCNL and the mutants were examined for their biological activities against Jurkat human leukemic T cells and the hypersensitive nematode Caenorhabditis elegans mutant strain pmk-1. rCNL was toxic against both, although the mutants were inactive. Thus, the bivalent carbohydrate-binding property of homodimeric CNL is essential for its activity, providing one of the rare pieces of evidence that certain activities of lectins are associated with their multivalency. PMID:22298779

Structure-property relationship of quinuclidinium surfactants--Towards multifunctional biologically active molecules.

PubMed

Skočibušić, Mirjana; Odžak, Renata; Štefanić, Zoran; Križić, Ivana; Krišto, Lucija; Jović, Ozren; Hrenar, Tomica; Primožič, Ines; Jurašin, Darija

2016-04-01

Motivated by diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths (CnQNOH; n=12, 14 and 16). The incorporation of non conventional hydroxyimino quinuclidinium headgroup and variation in alkyl chain length affects hydrophilic-hydrophobic balance of surfactant molecule and thereby physicochemical properties important for its application. Therefore, newly synthesized surfactants were characterized by the combination of different experimental techniques: X-ray analysis, potentiometry, electrical conductivity, surface tension and dynamic light scattering measurements, as well as antimicrobial susceptibility tests. Comprehensive investigation of CnQNOH surfactants enabled insight into structure-property relationship i.e., way in which the arrangement of surfactant molecules in the crystal phase correlates with their solution behavior and biologically activity. The synthesized CnQNOH surfactants exhibited high adsorption efficiency and relatively low critical micelle concentrations. In addition, all investigated compounds showed very potent and promising activity against Gram-positive and clinically relevant Gram-negative bacterial strains compared to conventional antimicrobial agents: tetracycline and gentamicin. The overall results indicate that bicyclic headgroup with oxime moiety, which affects both hydrophilicity and hydrophobicity of CnQNOH molecule in addition to enabling hydrogen bonding, has dominant effect on crystal packing and physicochemical properties. The unique structural features of cationic surfactants with hydroxyimino quinuclidine headgroup along with diverse biological activity have made them promising structures in novel drug discovery. Obtained fundamental understanding how combination of different functionalities in a single surfactant molecule affects its physicochemical properties represents a good starting point for further biological research. Copyright © 2015 Elsevier B.V. All rights reserved.

Triazole nucleoside derivatives bearing aryl functionalities on the nucleobases show antiviral and anticancer activity.

PubMed

Xia, Yi; Qu, Fanqi; Peng, Ling

2010-08-01

Synthetic nucleoside mimics are important candidates in the searing for antiviral and anticancer drugs. Ribavirin, the first antiviral nucleoside drug, is unique in its antiviral activity with mutilple modes of action, which are mainly due to its special triazole heterocycle as nucleobase. Additionally, introducing aromatic functionalities to the nucleobase is able to confer novel mechanisms of action for nucleoside mimics. With the aim to combine the special characteristics of unnatural triazole heterocycles with those of the appended aromatic groups on the nucleobases, novel 1,2,4-triazole nucleoside analogs bearing aromatic moieties were designed and developed. The present short review summarizes the molecular design, chemical synthesis and biological activity of these triazole nucleoside analogs. Indeed, the discovery of antiviral and anticancer activities shown by these triazole nucleosides as well as the new mechanism underlying the biological activity by one of the anticancer leads has validated the rationale for molecular design and impacted us to further explore the concept with the aim of developing structurally novel nucleoside drug candidates with new modes of action.

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

PubMed Central

Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

Facial expressions of emotion are not culturally universal.

PubMed

Jack, Rachael E; Garrod, Oliver G B; Yu, Hui; Caldara, Roberto; Schyns, Philippe G

2012-05-08

Since Darwin's seminal works, the universality of facial expressions of emotion has remained one of the longest standing debates in the biological and social sciences. Briefly stated, the universality hypothesis claims that all humans communicate six basic internal emotional states (happy, surprise, fear, disgust, anger, and sad) using the same facial movements by virtue of their biological and evolutionary origins [Susskind JM, et al. (2008) Nat Neurosci 11:843-850]. Here, we refute this assumed universality. Using a unique computer graphics platform that combines generative grammars [Chomsky N (1965) MIT Press, Cambridge, MA] with visual perception, we accessed the mind's eye of 30 Western and Eastern culture individuals and reconstructed their mental representations of the six basic facial expressions of emotion. Cross-cultural comparisons of the mental representations challenge universality on two separate counts. First, whereas Westerners represent each of the six basic emotions with a distinct set of facial movements common to the group, Easterners do not. Second, Easterners represent emotional intensity with distinctive dynamic eye activity. By refuting the long-standing universality hypothesis, our data highlight the powerful influence of culture on shaping basic behaviors once considered biologically hardwired. Consequently, our data open a unique nature-nurture debate across broad fields from evolutionary psychology and social neuroscience to social networking via digital avatars.

Facial expressions of emotion are not culturally universal

PubMed Central

Jack, Rachael E.; Garrod, Oliver G. B.; Yu, Hui; Caldara, Roberto; Schyns, Philippe G.

2012-01-01

Since Darwin’s seminal works, the universality of facial expressions of emotion has remained one of the longest standing debates in the biological and social sciences. Briefly stated, the universality hypothesis claims that all humans communicate six basic internal emotional states (happy, surprise, fear, disgust, anger, and sad) using the same facial movements by virtue of their biological and evolutionary origins [Susskind JM, et al. (2008) Nat Neurosci 11:843–850]. Here, we refute this assumed universality. Using a unique computer graphics platform that combines generative grammars [Chomsky N (1965) MIT Press, Cambridge, MA] with visual perception, we accessed the mind’s eye of 30 Western and Eastern culture individuals and reconstructed their mental representations of the six basic facial expressions of emotion. Cross-cultural comparisons of the mental representations challenge universality on two separate counts. First, whereas Westerners represent each of the six basic emotions with a distinct set of facial movements common to the group, Easterners do not. Second, Easterners represent emotional intensity with distinctive dynamic eye activity. By refuting the long-standing universality hypothesis, our data highlight the powerful influence of culture on shaping basic behaviors once considered biologically hardwired. Consequently, our data open a unique nature–nurture debate across broad fields from evolutionary psychology and social neuroscience to social networking via digital avatars. PMID:22509011

Can Carbon Nanotubes Deliver on Their Promise in Biology? Harnessing Unique Properties for Unparalleled Applications.

PubMed

Serpell, Christopher J; Kostarelos, Kostas; Davis, Benjamin G

2016-04-27

Carbon nanotubes (CNTs) are cylindrical sheets of hexagonally ordered carbon atoms, giving tubes with diameters on the order of a few nanometers and lengths typically in the micrometer range. They may be single- or multiwalled (SWCNTs and MWCNTs respectively). Since the seminal report of their synthesis in 1991, CNTs have fascinated scientists of all stripes. Physicists have been intrigued by their electrical, thermal, and vibrational potential. Materials scientists have worked on integrating them into ultrastrong composites and electronic devices, while chemists have been fascinated by the effects of curvature on reactivity and have developed new synthesis and purification techniques. However, to date no large-scale, real-life biotechnological CNT breakthrough has been industrially adopted and it is proving difficult to justify taking these materials forward into the clinic. We believe that these challenges are not the end of the story, but that a viable carbon nanotube biotechnology is one in which the unique properties of nanotubes bring about an effect that would be otherwise impossible. In this Outlook, we therefore seek to reframe the field by highlighting those biological applications in which the singular properties of CNTs provide some entirely new activity or biological effect as a pointer to "what could be".

The Pig PeptideAtlas: A resource for systems biology in animal production and biomedicine.

PubMed

Hesselager, Marianne O; Codrea, Marius C; Sun, Zhi; Deutsch, Eric W; Bennike, Tue B; Stensballe, Allan; Bundgaard, Louise; Moritz, Robert L; Bendixen, Emøke

2016-02-01

Biological research of Sus scrofa, the domestic pig, is of immediate relevance for food production sciences, and for developing pig as a model organism for human biomedical research. Publicly available data repositories play a fundamental role for all biological sciences, and protein data repositories are in particular essential for the successful development of new proteomic methods. Cumulative proteome data repositories, including the PeptideAtlas, provide the means for targeted proteomics, system-wide observations, and cross-species observational studies, but pigs have so far been underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within the veterinary proteomics domain, and this article demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM assays, which are equally important for progress in research that supports farm animal production and veterinary health, as for developing pig models with relevance to human health research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Pig PeptideAtlas: a resource for systems biology in animal production and biomedicine

PubMed Central

Hesselager, Marianne O.; Codrea, Marius C.; Sun, Zhi; Deutsch, Eric W.; Bennike, Tue B.; Stensballe, Allan; Bundgaard, Louise; Moritz, Robert L.; Bendixen, Emøke

2016-01-01

Biological research of Sus scrofa, the domestic pig, is of immediate relevance for food production sciences, and for developing pig as a model organism for human biomedical research. Publicly available data repositories play a fundamental role for all biological sciences, and protein data repositories are in particular essential for the successful development of new proteomic methods. Cumulative proteome data repositories, including the PeptideAtlas, provide the means for targeted proteomics, system wide observations, and cross species observational studies, but pigs have so far been underrepresented in existing repositories. We here present a significantly improved build of the Pig PeptideAtlas, which includes pig proteome data from 25 tissues and three body fluid types mapped to 7139 canonical proteins. The content of the Pig PeptideAtlas reflects actively ongoing research within the veterinary proteomics domain, and this manuscript demonstrates how the expression of isoform-unique peptides can be observed across distinct tissues and body fluids. The Pig PeptideAtlas is a unique resource for use in animal proteome research, particularly biomarker discovery and for preliminary design of SRM assays, which are equally important for progress in research that supports farm animal production and veterinary health, as for developing pig models with relevance to human health research. PMID:26699206

High yield bacterial expression, purification and characterisation of bioactive Human Tousled-like Kinase 1B involved in cancer.

PubMed

Bhoir, Siddhant; Shaik, Althaf; Thiruvenkatam, Vijay; Kirubakaran, Sivapriya

2018-03-19

Human Tousled-like kinases (TLKs) are highly conserved serine/threonine protein kinases responsible for cell proliferation, DNA repair, and genome surveillance. Their possible involvement in cancer via efficient DNA repair mechanisms have made them clinically relevant molecular targets for anticancer therapy. Innovative approaches in chemical biology have played a key role in validating the importance of kinases as molecular targets. However, the detailed understanding of the protein structure and the mechanisms of protein-drug interaction through biochemical and biophysical techniques demands a method for the production of an active protein of exceptional stability and purity on a large scale. We have designed a bacterial expression system to express and purify biologically active, wild-type Human Tousled-like Kinase 1B (hTLK1B) by co-expression with the protein phosphatase from bacteriophage λ. We have obtained remarkably high amounts of the soluble and homogeneously dephosphorylated form of biologically active hTLK1B with our unique, custom-built vector design strategy. The recombinant hTLK1B can be used for the structural studies and may further facilitate the development of new TLK inhibitors for anti-cancer therapy using a structure-based drug design approach.

Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

PubMed Central

Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

2016-01-01

Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances. PMID:27023571

Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases

PubMed Central

Gul, Waseem; Hamann, Mark T.

2016-01-01

The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets. Historically marine natural products have largely been explored as anticancer agents. The indole alkaloids are a class of marine natural products that show unique promise in the development of new drug leads. This report reviews the literature on indole alkaloids of marine origin and also highlights our own research. Specific biological activities of indole alkaloids presented here include: cytotoxicity, antiviral, antiparasitic, anti-inflammatory, serotonin antagonism, Ca-releasing, calmodulin antagonism, and other pharmacological activities. PMID:16236327

Ganoderma pfeifferi--A European relative of Ganoderma lucidum.

PubMed

Lindequist, Ulrike; Jülich, Wolf-Dieter; Witt, Sabine

2015-06-01

In contrast to well-studied and broadly used Ganoderma species, such as Ganoderma lucidum and Ganoderma applanatum, knowledge regarding Ganoderma pfeifferi is very limited. Herein is an overview of the phytochemistry, biological activities and possible applications of this mushroom species. In addition to triterpenoids and polysaccharides, G. pfeifferi contains unique sesquiterpenoids and other small molecular weight compounds. Some of these compounds exhibit remarkable antimicrobial activities in vitro and in vivo against multi-resistant bacteria, such as MRSA. Antiviral properties, UV-protection abilities and other activities are also known. Potential issues arising from the conversion of research results into practical applications are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phoretic Self-Propulsion

NASA Astrophysics Data System (ADS)

Moran, Jeffrey L.; Posner, Jonathan D.

2017-01-01

It is well-known that micro- and nanoparticles can move by phoretic effects in response to externally imposed gradients of scalar quantities such as chemical concentration or electric potential. A class of active colloids can propel themselves through aqueous media by generating local gradients of concentration and electrical potential via surface reactions. Phoretic active colloids can be controlled using external stimuli and can mimic collective behaviors exhibited by many biological swimmers. Low-Reynolds number physicochemical hydrodynamics imposes unique challenges and constraints that must be understood for the practical potential of active colloids to be realized. Here, we review the rich physics underlying the operation of phoretic active colloids, describe their interactions and collective behaviors, and discuss promising directions for future research.

The Chemical Biology of HNO Signaling

PubMed Central

Bianco, Christopher L.; Toscano, John P.; Bartberger, Michael D.; Fukuto, Jon M.

2016-01-01

Nitroxyl (HNO) is a simple molecule with significant potential as a pharmacological agent. For example, its use in the possible treatment of heart failure has received recent attention due to its unique therapeutic properties. Recent progress has been made on the elucidation of the mechanisms associated with its biological signaling. Importantly, the biochemical mechanisms described for HNO bioactivity are consistent with its unique and novel chemical properties/reactivity. To date, much of the biology of HNO can be associated with interactions and modification of important regulatory thiol proteins. Herein will be provided a description of HNO chemistry and how this chemistry translates to some of its reported biological effects. PMID:27555493

[Cooperations between biology laboratories of the establishments of healthcare].

PubMed

Burnat, Pascal; Payen, Catherine; Mérens, Audrey; Ceppa, Franck; Renard, Christophe

2013-01-01

In France, the cooperations between biological laboratories of the healthcare establishments increased after those realized in the private laboratories. The biologists are confronted with various hypotheses of organization. They are often complex because they may preserve the quality of the care and their continuity while realizing financial economies. These economies are mostly based on the global reduction in the staff and in the equipments by mutualising the biological tests with varying degrees. We describe the various elements to be taken into account (staff, activities, budget, quality, transport, materials) and propose many scenarios of cooperations, from a unique central shape to the transfer of very specialized tests, with their advantages and their inconveniences. The management of human aspects in these cooperations is determining to facilitate their success as well as a reliable preliminary inventory of fixtures.

The herpesvirus proteases as targets for antiviral chemotherapy.

PubMed

Waxman, L; Darke, P L

2000-01-01

Viruses of the family Herpesviridae are responsible for a diverse set of human diseases. The available treatments are largely ineffective, with the exception of a few drugs for treatment of herpes simplex virus (HSV) infections. For several members of this DNA virus family, advances have been made recently in the biochemistry and structural biology of the essential viral protease, revealing common features that may be possible to exploit in the development of a new class of anti-herpesvirus agents. The herpesvirus proteases have been identified as belonging to a unique class of serine protease, with a Ser-His-His catalytic triad. A new, single domain protein fold has been determined by X-ray crystallography for the proteases of at least three different herpesviruses. Also unique for serine proteases, dimerization has been shown to be required for activity of the cytomegalovirus and HSV proteases. The dimerization requirement seriously impacts methods needed for productive, functional analysis and inhibitor discovery. The conserved functional and catalytic properties of the herpesvirus proteases lead to common considerations for this group of proteases in the early phases of inhibitor discovery. In general, classical serine protease inhibitors that react with active site residues do not readily inactivate the herpesvirus proteases. There has been progress however, with activated carbonyls that exploit the selective nucleophilicity of the active site serine. In addition, screening of chemical libraries has yielded novel structures as starting points for drug development. Recent crystal structures of the herpesvirus proteases now allow more direct interpretation of ligand structure-activity relationships. This review first describes basic functional aspects of herpesvirus protease biology and enzymology. Then we discuss inhibitors identified to date and the prospects for their future development.

New medications for substance use disorders: challenges and opportunities.

PubMed

Volkow, Nora D; Skolnick, Phil

2012-01-01

An increased understanding of the biological mechanisms underlying the process of addiction has led to unique molecular targets and strategies for pharmacotherapies against addiction. However, the successful translation of these discoveries will require: 1) a more active engagement of the pharmaceutical sector, 2) partnership with regulatory agencies to arrive at meaningful outcomes for medication approval and 3) a greater involvement of the healthcare system in the screening and treatment of substance use disorders.

The unconventional antimicrobial peptides of the classical propionibacteria.

PubMed

Faye, Therese; Holo, Helge; Langsrud, Thor; Nes, Ingolf F; Brede, Dag A

2011-02-01

The classical propionibacteria produce genetically unique antimicrobial peptides, whose biological activities are without equivalents, and to which there are no homologous sequences in public databases. In this review, we summarize the genetics, biochemistry, biosynthesis, and biological activities of three extensively studied antimicrobial peptides from propionibacteria. The propionicin T1 peptide constitutes a bona fide example of an unmodified general secretory pathway (sec)-dependent bacteriocin, which is bactericidal towards all tested species of propionibacteria except Propionibacterium freudenreichii. The PAMP antimicrobial peptide represents a novel concept within bacterial antagonism, where an inactive precursor protein is secreted in large amounts, and which activation appears to rely on subsequent processing by proteases in its resident milieu. Propionicin F is a negatively charged bacteriocin that displays an intraspecies bactericidal inhibition spectrum. The biosynthesis of propionicin F appears to proceed through a series of unusual events requiring both N- and C-terminal processing of a precursor protein, which probably requires the radical SAM superfamily enzyme PcfB.

Advances in chemical labeling of proteins in living cells.

PubMed

Yan, Qi; Bruchez, Marcel P

2015-04-01

The pursuit of quantitative biological information via imaging requires robust labeling approaches that can be used in multiple applications and with a variety of detectable colors and properties. In addition to conventional fluorescent proteins, chemists and biologists have come together to provide a range of approaches that combine dye chemistry with the convenience of genetic targeting. This hybrid-tagging approach amalgamates the rational design of properties available through synthetic dye chemistry with the robust biological targeting available with genetic encoding. In this review, we discuss the current range of approaches that have been exploited for dye targeting or for targeting and activation and some of the recent applications that are uniquely permitted by these hybrid-tagging approaches.

Designing Uniquely Addressable Bio-orthogonal Synthetic Scaffolds for DNA and RNA Origami.

PubMed

Kozyra, Jerzy; Ceccarelli, Alessandro; Torelli, Emanuela; Lopiccolo, Annunziata; Gu, Jing-Ying; Fellermann, Harold; Stimming, Ulrich; Krasnogor, Natalio

2017-07-21

Nanotechnology and synthetic biology are rapidly converging, with DNA origami being one of the leading bridging technologies. DNA origami was shown to work well in a wide array of biotic environments. However, the large majority of extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus severely limiting its future applicability as a bio-orthogonal nanotechnology platform. In this paper we present the design of biologically inert (i.e., "bio-orthogonal") origami scaffolds. The synthetic scaffolds have the additional advantage of being uniquely addressable (unlike biologically derived ones) and hence are better optimized for high-yield folding. We demonstrate our fully synthetic scaffold design with both DNA and RNA origamis and describe a protocol to produce these bio-orthogonal and uniquely addressable origami scaffolds.

Pharmaceutically active secondary metabolites of marine actinobacteria.

PubMed

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

Characterization of 2,3-diarylxanthones by electrospray mass spectrometry: gas-phase chemistry versus known antioxidant activity properties.

PubMed

Silva, Eduarda M P; Barros, Cristina M R F; Santos, Clementina M M; Barros, António S; Domingues, M Rosário M; Silva, Artur M S

2016-10-30

Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored. Protonated xanthones XH1-9 were generated in the gas phase by electrospray ionization (ESI) and the main fragmentation pathways of the protonated XH1-9 formed due to collision-induced dissociation (CID) were investigated. In the CID-MS/MS spectra of [M+H](+) ions of XH1, XH2 and XH4 the product ions formed due to H2 O elimination corresponding to the base peak of the spectra. For the remaining six xanthones (XH3, XH5-9), showing the most promising biological profile, the product ion produced with the highest relative abundance (RA) corresponded to the one formed through concomitant loss of H2 O plus CO. Indicative of an inexistent or lower biological activity is the combined loss of CO plus O unique to the CID-MS/MS spectra of XH1, XH2, XH4, and XH5. The product ion formed by loss of 64 Da (concomitant loss of two molecules of H2 O plus CO) is only observed for xanthones containing a catechol unit (XH3 and XH6-9). This product ion has the highest RA for the most potent scavenger of reactive oxygen and nitrogen species XH9 that contains two of these catechol moieties. A strong relationship between some of the biological activities of the studied 2,3-diarylxanthones and their ESI-MS/MS fragmentation spectra was found. The multivariate statistical analysis results suggest that the selected MS features are related to the important biological features. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts

PubMed Central

Parages, María L.; Gutiérrez-Barranquero, José A.; Reen, F. Jerry; Dobson, Alan D.W.; O’Gara, Fergal

2016-01-01

In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries as a valuable and promising source of novel bioactive compounds. Marine biodiscovery programmes have begun to reveal the extent of novel compounds encoded within the enormous bacterial richness and diversity of the marine ecosystem. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel biocatalytic activities. With the growing need for green alternatives to industrial processes, and the unique transformations which nature is capable of performing, marine biocatalysts have the potential to markedly improve current industrial pipelines. Furthermore, biocatalysts are known to possess chiral selectivity and specificity, a key focus of pharmaceutical drug design. In this review, we discuss how the explosion in genomics based sequence analysis, allied with parallel developments in synthetic and molecular biology, have the potential to fast-track the discovery and subsequent improvement of a new generation of marine biocatalysts. PMID:27007381

Supervised Semi-Automated Data Analysis Software for Gas Chromatography / Differential Mobility Spectrometry (GC/DMS) Metabolomics Applications.

PubMed

Peirano, Daniel J; Pasamontes, Alberto; Davis, Cristina E

2016-09-01

Modern differential mobility spectrometers (DMS) produce complex and multi-dimensional data streams that allow for near-real-time or post-hoc chemical detection for a variety of applications. An active area of interest for this technology is metabolite monitoring for biological applications, and these data sets regularly have unique technical and data analysis end user requirements. While there are initial publications on how investigators have individually processed and analyzed their DMS metabolomic data, there are no user-ready commercial or open source software packages that are easily used for this purpose. We have created custom software uniquely suited to analyze gas chromatograph / differential mobility spectrometry (GC/DMS) data from biological sources. Here we explain the implementation of the software, describe the user features that are available, and provide an example of how this software functions using a previously-published data set. The software is compatible with many commercial or home-made DMS systems. Because the software is versatile, it can also potentially be used for other similarly structured data sets, such as GC/GC and other IMS modalities.

Structural Analysis of PTM Hotspots (SAPH-ire)--A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families.

PubMed

Dewhurst, Henry M; Choudhury, Shilpa; Torres, Matthew P

2015-08-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)--a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits--conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit-N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells.

PubMed

Pellett, Sabine; Du, Zhong-wei; Pier, Christina L; Tepp, William H; Zhang, Su-chun; Johnson, Eric A

2011-01-07

Botulinum neurotoxins (BoNTs), the most poisonous protein toxins known, represent a serious bioterrorism threat but are also used as a unique and important bio-pharmaceutical to treat an increasing myriad of neurological disorders. The only currently accepted detection method by the United States Food and Drug Administration for biological activity of BoNTs and for potency determination of pharmaceutical preparations is the mouse bioassay (MBA). Recent advances have indicated that cell-based assays using primary neuronal cells can provide an equally sensitive and robust detection platform as the MBA to reliably and quantitatively detect biologically active BoNTs. This study reports for the first time a BoNT detection assay using mouse embryonic stem cells to produce a neuronal cell culture. The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA. Published by Elsevier Inc.

New Frontiers and Challenges for Single-Cell Electrochemical Analysis.

PubMed

Zhang, Jingjing; Zhou, Junyu; Pan, Rongrong; Jiang, Dechen; Burgess, James D; Chen, Hong-Yuan

2018-02-23

Previous measurements of cell populations might obscure many important cellular differences, and new strategies for single-cell analyses are urgently needed to re-examine these fundamental biological principles for better diagnosis and treatment of diseases. Electrochemistry is a robust technique for the analysis of single living cells that has the advantages of minor interruption of cellular activity and provides the capability of high spatiotemporal resolution. The achievements of the past 30 years have revealed significant information about the exocytotic events of single cells to elucidate the mechanisms of cellular activity. Currently, the rapid developments of micro/nanofabrication and optoelectronic technologies drive the development of multifunctional electrodes and novel electrochemical approaches with higher resolution for single cells. In this Perspective, three new frontiers in this field, namely, electrochemical microscopy, intracellular analysis, and single-cell analysis in a biological system (i.e., neocortex and retina), are reviewed. The unique features and remaining challenges of these techniques are discussed.

Human Uterine Cervical Stromal Stem Cells (hUCESCs): Why and How they Exert their Antitumor Activity.

PubMed

Schneider, José; Eiró, Noemí; Pérez-Fernández, Román; Martínez-Ordóñez, Anxo; Vizoso, Francisco

Our research team has recently isolated and characterized a new stromal stem cell line (hUCESCs) obtained from cytological smears, as routinely performed for cervical cancer screening. We have, furthermore, described that both hUCESCs directly, as well as the secretome contained in the conditioned medium used for growing them (hUCESCs-CM) have potent antitumoral, anti-inflammatory, antibiotic, antimycotic and re-epitheliasation-enhancing properties. The scientific explanation our team proposes for these pleiotropic effects are directly related to the site of origin of hUCESCs, the human cervical transition zone, which has unique features that biologically justify the different actions of hUCESCs and hUCESCs-CM. We, herein, expose our working theory for the biological activity of hUCESCs and hUCESCs-CM. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Induced Fit in Protein Multimerization: The HFBI Case

PubMed Central

Riccardi, Laura

2016-01-01

Hydrophobins, produced by filamentous fungi, are small amphipathic proteins whose biological functions rely on their unique surface-activity properties. Understanding the mechanistic details of the multimerization process is of primary importance to clarify the interfacial activity of hydrophobins. We used free energy calculations to study the role of a flexible β-hairpin in the multimerization process in hydrophobin II from Trichoderma reesei (HFBI). We characterized how the displacement of this β-hairpin controls the stability of the monomers/dimers/tetramers in solution. The regulation of the oligomerization equilibrium of HFBI will necessarily affect its interfacial properties, fundamental for its biological function and for technological applications. Moreover, we propose possible routes for the multimerization process of HFBI in solution. This is the first case where a mechanism by which a flexible loop flanking a rigid patch controls the protein-protein binding equilibrium, already known for proteins with charged binding hot-spots, is described within a hydrophobic patch. PMID:27832079

Connecting Biology to Electronics: Molecular Communication via Redox Modality.

PubMed

Liu, Yi; Li, Jinyang; Tschirhart, Tanya; Terrell, Jessica L; Kim, Eunkyoung; Tsao, Chen-Yu; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

2017-12-01

Biology and electronics are both expert at for accessing, analyzing, and responding to information. Biology uses ions, small molecules, and macromolecules to receive, analyze, store, and transmit information, whereas electronic devices receive input in the form of electromagnetic radiation, process the information using electrons, and then transmit output as electromagnetic waves. Generating the capabilities to connect biology-electronic modalities offers exciting opportunities to shape the future of biosensors, point-of-care medicine, and wearable/implantable devices. Redox reactions offer unique opportunities for bio-device communication that spans the molecular modalities of biology and electrical modality of devices. Here, an approach to search for redox information through an interactive electrochemical probing that is analogous to sonar is adopted. The capabilities of this approach to access global chemical information as well as information of specific redox-active chemical entities are illustrated using recent examples. An example of the use of synthetic biology to recognize external molecular information, process this information through intracellular signal transduction pathways, and generate output responses that can be detected by electrical modalities is also provided. Finally, exciting results in the use of redox reactions to actuate biology are provided to illustrate that synthetic biology offers the potential to guide biological response through electrical cues. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The material and biological characteristics of osteoinductive calcium phosphate ceramics

PubMed Central

Tang, Zhurong; Li, Xiangfeng; Tan, Yanfei

2018-01-01

Abstract The discovery of osteoinductivity of calcium phosphate (Ca-P) ceramics has set an enduring paradigm of conferring biological regenerative activity to materials with carefully designed structural characteristics. The unique phase composition and porous structural features of osteoinductive Ca-P ceramics allow it to interact with signaling molecules and extracellular matrices in the host system, creating a local environment conducive to new bone formation. Mounting evidence now indicate that the osteoinductive activity of Ca-P ceramics is linked to their physicochemical and three-dimensional structural properties. Inspired by this conceptual breakthrough, many laboratories have shown that other materials can be also enticed to join the rank of tissue-inducing biomaterials, and besides the bones, other tissues such as cartilage, nerves and blood vessels were also regenerated with the assistance of biomaterials. Here, we give a brief historical recount about the discovery of the osteoinductivity of Ca-P ceramics, summarize the underlying material factors and biological characteristics, and discuss the mechanism of osteoinduction concerning protein adsorption, and the interaction with different types of cells, and the involvement of the vascular and immune systems. PMID:29423267

Company Profile: Selventa, Inc.

PubMed

Fryburg, David A; Latino, Louis J; Tagliamonte, John; Kenney, Renee D; Song, Diane H; Levine, Arnold J; de Graaf, David

2012-08-01

Selventa, Inc. (MA, USA) is a biomarker discovery company that enables personalized healthcare. Originally founded as Genstruct, Inc., Selventa has undergone significant evolution from a technology-based service provider to an active partner in the development of diagnostic tests, functioning as a molecular dashboard of disease activity using a unique platform. As part of that evolution, approximately 2 years ago the company was rebranded as Selventa to reflect its new identity and mission. The contributions to biomedical research by Selventa are based on in silico, reverse-engineering methods to determine biological causality. That is, given a set of in vitro or in vivo biological observations, which biological mechanisms can explain the measured results? Facilitated by a large and carefully curated knowledge base, these in silico methods generated new insights into the mechanisms driving a disease. As Selventa's methods would enable biomarker discovery and be directly applicable to generating novel diagnostics, the scientists at Selventa have focused on the development of predictive biomarkers of response in autoimmune and oncologic diseases. Selventa is presently building a portfolio of independent, as well as partnered, biomarker projects with the intention to create diagnostic tests that predict response to therapy.

Discrimination of unique biological communities in the Mississippi lignite belt

NASA Technical Reports Server (NTRS)

Miller, W. F. (Principal Investigator); Cutler, J. D.

1981-01-01

Small scale hardcopy LANDSAT prints were manually interpreted and color infrared aerial photography was obtained in an effort to identify and map large contiguous areas of old growth hardwood stands within Mississippi's lignite belt which do not exhibit signs of recent disturbance by agriculture, grazing, timber harvesting, fire, or any natural catastrophe, and which may, therefore, contain unique or historical ecological habitat types. An information system using land cover classes derived from digital LANDSAT data and containing information on geology, hydrology, soils, and cultural activities was developed. Using computer-assisted land cover classifications, all hardwood remnants in the study area which are subject to possible disturbance from surface mining were determined. Twelve rare plants were also identified by botanists.

Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis.

PubMed

Armbruster, Chelsie E; Mobley, Harry L T

2012-11-01

Proteus mirabilis, named for the Greek god who changed shape to avoid capture, has fascinated microbiologists for more than a century with its unique swarming differentiation, Dienes line formation and potent urease activity. Transcriptome profiling during both host infection and swarming motility, coupled with the availability of the complete genome sequence for P. mirabilis, has revealed the occurrence of interbacterial competition and killing through a type VI secretion system, and the reciprocal regulation of adhesion and motility, as well as the intimate connections between metabolism, swarming and virulence. This Review addresses some of the unique and recently described aspects of P. mirabilis biology and pathogenesis, and emphasizes the potential role of this bacterium in single-species and polymicrobial urinary tract infections.

Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis

PubMed Central

Armbruster, Chelsie E.; Mobley, Harry L. T.

2013-01-01

Proteus mirabilis, named for the Greek god who changed shape to avoid capture, has fascinated microbiologists for more than a century with its unique swarming differentiation, Dienes line formation and potent urease activity. Transcriptome profiling during both host infection and swarming motility, coupled with the availability of the complete genome sequence for P. mirabilis, has revealed the occurrence of interbacterial competition and killing through a type VI secretion system, and the reciprocal regulation of adhesion and motility, as well as the intimate connections between metabolism, swarming and virulence. This Review addresses some of the unique and recently described aspects of P. mirabilis biology and pathogenesis, and emphasizes the potential role of this bacterium in single- species and polymicrobial urinary tract infections. PMID:23042564

A Recombinant Adenovirus Expressing Ovine Interferon Tau Prevents Influenza Virus-Induced Lethality in Mice.

PubMed

Martín, V; Pascual, E; Avia, M; Rangel, G; de Molina, A; Alejo, A; Sevilla, N

2016-01-06

Ovine interferon tau (IFN-τ) is a unique type I interferon with low toxicity and a broad host range in vivo. We report the generation of a nonreplicative recombinant adenovirus expressing biologically active IFN-τ. Using the B6.A2G-Mx1 mouse model, we showed that single-dose intranasal administration of recombinant Ad5-IFN-τ can effectively prevent lethality and disease induced by highly virulent hv-PR8 influenza virus by activating the interferon response and preventing viral replication. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Antimicrobial Activity of Basil, Oregano, and Thyme Essential Oils.

PubMed

Sakkas, Hercules; Papadopoulou, Chrissanthy

2017-03-28

For centuries, plants have been used for a wide variety of purposes, from treating infectious diseases to food preservation and perfume production. Presently, the increasing resistance of microorganisms to currently used antimicrobials in combination with the appearance of emerging diseases requires the urgent development of new, more effective drugs. Plants, due to the large biological and structural diversity of their components, constitute a unique and renewable source for the discovery of new antibacterial, antifungal, and antiparasitic compounds. In the present paper, the history, composition, and antimicrobial activities of the basil, oregano, and thyme essential oils are reviewed.

Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum

PubMed Central

Vieira-de-Abreu, Adriana; Campbell, Robert A.; Weyrich, Andrew S.

2015-01-01

Platelets are chief effector cells in hemostasis. In addition, however, their specializations include activities and intercellular interactions that make them key effectors in inflammation and in the continuum of innate and adaptive immunity. This review focuses on the immune features of human platelets and platelets from experimental animals and on interactions between inflammatory, immune, and hemostatic activities of these anucleate but complex and versatile cells. The experimental findings and evidence for physiologic immune functions include previously unrecognized biologic characteristics of platelets and are paralleled by new evidence for unique roles of platelets in inflammatory, immune, and thrombotic diseases. PMID:21818701

Hyperthermia Using Nanoparticles – Promises and Pitfalls

PubMed Central

Kaur, Punit; Aliru, Maureen L.; Chadha, Awalpreet S.; Asea, Alexzander; Krishnan, Sunil

2016-01-01

An ever-increasing body of literature affirms the physical and biological basis for sensitization of tumors to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fueled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalizes on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia. PMID:26757879

Hyperthermia using nanoparticles--Promises and pitfalls.

PubMed

Kaur, Punit; Aliru, Maureen L; Chadha, Awalpreet S; Asea, Alexzander; Krishnan, Sunil

2016-01-01

An ever-increasing body of literature affirms the physical and biological basis for sensitisation of tumours to conventional therapies such as chemotherapy and radiation therapy by mild temperature hyperthermia. This knowledge has fuelled the efforts to attain, maintain, measure and monitor temperature via technological advances. A relatively new entrant in the field of hyperthermia is nanotechnology which capitalises on locally injected or systemically administered nanoparticles that are activated by extrinsic energy sources to generate heat. This review describes the kinds of nanoparticles available for hyperthermia generation, their activation sources, their characteristics, and the unique opportunities and challenges with nanoparticle-mediated hyperthermia.

Direct electron transfer of glucose oxidase on carbon nanotubes

NASA Astrophysics Data System (ADS)

Guiseppi-Elie, Anthony; Lei, Chenghong; Baughman, Ray H.

2002-10-01

In this report, exploitation of the unique properties of single-walled carbon nanotubes (SWNT) leads to the achievement of direct electron transfer with the redox active centres of adsorbed oxidoreductase enzymes. Flavin adenine dinucleotide (FAD), the redox active prosthetic group of flavoenzymes that catalyses important biological redox reactions and the flavoenzyme glucose oxidase (GOx), were both found to spontaneously adsorb onto carbon nanotube bundles. Both FAD and GOx were found to spontaneously adsorb to unannealed carbon nanotubes that were cast onto glassy carbon electrodes and to display quasi-reversible one-electron transfer. Similarly, GOx was found to spontaneously adsorb to annealed, single-walled carbon nanotube paper and to display quasi-reversible one-electron transfer. In particular, GOx immobilized in this way was shown, in the presence of glucose, to maintain its substrate-specific enzyme activity. It is believed that the tubular fibrils become positioned within tunnelling distance of the cofactors with little consequence to denaturation. The combination of SWNT with redox active enzymes would appear to offer an excellent and convenient platform for a fundamental understanding of biological redox reactions as well as the development of reagentless biosensors and nanobiosensors.

Tyrosine Kinase Signaling in Clear Cell and Papillary Renal Cell Carcinoma Revealed by Mass Spectrometry-Based Phosphotyrosine Proteomics.

PubMed

Haake, Scott M; Li, Jiannong; Bai, Yun; Kinose, Fumi; Fang, Bin; Welsh, Eric A; Zent, Roy; Dhillon, Jasreman; Pow-Sang, Julio M; Chen, Y Ann; Koomen, John M; Rathmell, W Kimryn; Fishman, Mayer; Haura, Eric B

2016-11-15

Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes. Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. To describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry-based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed. Among the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, whereas DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets. Tyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology among kidney cancer subtypes. Clin Cancer Res; 22(22); 5605-16. ©2016 AACR. ©2016 American Association for Cancer Research.

Biological and pharmacological evaluation of dimethoxycurcumin: A metabolically stable curcumin analogue with a promising therapeutic potential.

PubMed

Teymouri, Manouchehr; Barati, Nastaran; Pirro, Matteo; Sahebkar, Amirhosein

2018-01-01

Dimethoxycurcumin (DiMC) is a synthetic analog of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anti-carcinogenic, and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structure-activity relationship (SAR) of curcumin. In this regard, tetrahydrocurcumin (THC), the reduced and biologically inert metabolite of curcumin, denotes the significance of the conjugated α,β diketone moiety for the curcumin activity. DiMC exerts unique molecular activities compared to curcumin, including induction of androgen receptor (AR) degradation and suppression of the transcription factor activator protein-1 (AP-1). The enhanced AR degradation on DiMC treatment suggests it as a novel anticancer agent against resistant tumors with androgenic etiology. Further, DiMC might be a potential treatment for acne vulgaris. DiMC induces epigenetic alteration more effectively than curcumin, although both showed no direct DNA hypomethylating activity. Given the metabolic stability, nanoparticulation of DiMC is more promising for in vivo effectiveness. However, studies in this regard are still in its infancy. In the current review, we portray the various molecular and biological functions of DiMC reported so far. Whenever possible, the efficiency is compared with curcumin and the reasons for DiMC being more metabolically stable are elaborated. We also provide future perspective investigations with respect to varying DiMC-nanoparticles. © 2016 Wiley Periodicals, Inc.

Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties

PubMed Central

Kemp, Melissa M; Kumar, Ashavani; Clement, Dylan; Ajayan, Pulickel; Mousa, Shaker

2009-01-01

Aims Silver nanoparticles exhibit unique antibacterial properties that make these ideal candidates for biological and medical applications. We utilized a clean method involving a single synthetic step to prepare silver nanoparticles that exhibit antimicrobial activity. Materials & methods These nanoparticles were prepared by reducing silver nitrate with diaminopyridinylated heparin (DAPHP) and hyaluronan (HA) polysaccharides and tested for their efficacy in inhibiting microbial growth. Results & discussion The resulting silver nanoparticles exhibit potent antimicrobial activity against Staphylococcus aureus and modest activity against Escherichia coli. Silver–HA showed greater antimicrobial activity than silver–DAPHP, while silver–glucose nanoparticles exhibited very weak antimicrobial activity. Neither HA nor DAPHP showed activity against S. aureus or E. coli. Conclusion These results suggest that DAPHP and HA silver nanoparticles have potential in antimicrobial therapeutic applications. PMID:19505245

Structural Analysis of PTM Hotspots (SAPH-ire) – A Quantitative Informatics Method Enabling the Discovery of Novel Regulatory Elements in Protein Families*

PubMed Central

Dewhurst, Henry M.; Choudhury, Shilpa; Torres, Matthew P.

2015-01-01

Predicting the biological function potential of post-translational modifications (PTMs) is becoming increasingly important in light of the exponential increase in available PTM data from high-throughput proteomics. We developed structural analysis of PTM hotspots (SAPH-ire)—a quantitative PTM ranking method that integrates experimental PTM observations, sequence conservation, protein structure, and interaction data to allow rank order comparisons within or between protein families. Here, we applied SAPH-ire to the study of PTMs in diverse G protein families, a conserved and ubiquitous class of proteins essential for maintenance of intracellular structure (tubulins) and signal transduction (large and small Ras-like G proteins). A total of 1728 experimentally verified PTMs from eight unique G protein families were clustered into 451 unique hotspots, 51 of which have a known and cited biological function or response. Using customized software, the hotspots were analyzed in the context of 598 unique protein structures. By comparing distributions of hotspots with known versus unknown function, we show that SAPH-ire analysis is predictive for PTM biological function. Notably, SAPH-ire revealed high-ranking hotspots for which a functional impact has not yet been determined, including phosphorylation hotspots in the N-terminal tails of G protein gamma subunits—conserved protein structures never before reported as regulators of G protein coupled receptor signaling. To validate this prediction we used the yeast model system for G protein coupled receptor signaling, revealing that gamma subunit–N-terminal tail phosphorylation is activated in response to G protein coupled receptor stimulation and regulates protein stability in vivo. These results demonstrate the utility of integrating protein structural and sequence features into PTM prioritization schemes that can improve the analysis and functional power of modification-specific proteomics data. PMID:26070665

A Unique Large-Scale Undergraduate Research Experience in Molecular Systems Biology for Non-Mathematics Majors

ERIC Educational Resources Information Center

Kappler, Ulrike; Rowland, Susan L.; Pedwell, Rhianna K.

2017-01-01

Systems biology is frequently taught with an emphasis on mathematical modeling approaches. This focus effectively excludes most biology, biochemistry, and molecular biology students, who are not mathematics majors. The mathematical focus can also present a misleading picture of systems biology, which is a multi-disciplinary pursuit requiring…

3D Printed Bionic Nanodevices.

PubMed

Kong, Yong Lin; Gupta, Maneesh K; Johnson, Blake N; McAlpine, Michael C

2016-06-01

The ability to three-dimensionally interweave biological and functional materials could enable the creation of bionic devices possessing unique and compelling geometries, properties, and functionalities. Indeed, interfacing high performance active devices with biology could impact a variety of fields, including regenerative bioelectronic medicines, smart prosthetics, medical robotics, and human-machine interfaces. Biology, from the molecular scale of DNA and proteins, to the macroscopic scale of tissues and organs, is three-dimensional, often soft and stretchable, and temperature sensitive. This renders most biological platforms incompatible with the fabrication and materials processing methods that have been developed and optimized for functional electronics, which are typically planar, rigid and brittle. A number of strategies have been developed to overcome these dichotomies. One particularly novel approach is the use of extrusion-based multi-material 3D printing, which is an additive manufacturing technology that offers a freeform fabrication strategy. This approach addresses the dichotomies presented above by (1) using 3D printing and imaging for customized, hierarchical, and interwoven device architectures; (2) employing nanotechnology as an enabling route for introducing high performance materials, with the potential for exhibiting properties not found in the bulk; and (3) 3D printing a range of soft and nanoscale materials to enable the integration of a diverse palette of high quality functional nanomaterials with biology. Further, 3D printing is a multi-scale platform, allowing for the incorporation of functional nanoscale inks, the printing of microscale features, and ultimately the creation of macroscale devices. This blending of 3D printing, novel nanomaterial properties, and 'living' platforms may enable next-generation bionic systems. In this review, we highlight this synergistic integration of the unique properties of nanomaterials with the versatility of extrusion-based 3D printing technologies to interweave nanomaterials and fabricate novel bionic devices.

3D Printed Bionic Nanodevices

PubMed Central

Kong, Yong Lin; Gupta, Maneesh K.; Johnson, Blake N.; McAlpine, Michael C.

2016-01-01

Summary The ability to three-dimensionally interweave biological and functional materials could enable the creation of bionic devices possessing unique and compelling geometries, properties, and functionalities. Indeed, interfacing high performance active devices with biology could impact a variety of fields, including regenerative bioelectronic medicines, smart prosthetics, medical robotics, and human-machine interfaces. Biology, from the molecular scale of DNA and proteins, to the macroscopic scale of tissues and organs, is three-dimensional, often soft and stretchable, and temperature sensitive. This renders most biological platforms incompatible with the fabrication and materials processing methods that have been developed and optimized for functional electronics, which are typically planar, rigid and brittle. A number of strategies have been developed to overcome these dichotomies. One particularly novel approach is the use of extrusion-based multi-material 3D printing, which is an additive manufacturing technology that offers a freeform fabrication strategy. This approach addresses the dichotomies presented above by (1) using 3D printing and imaging for customized, hierarchical, and interwoven device architectures; (2) employing nanotechnology as an enabling route for introducing high performance materials, with the potential for exhibiting properties not found in the bulk; and (3) 3D printing a range of soft and nanoscale materials to enable the integration of a diverse palette of high quality functional nanomaterials with biology. Further, 3D printing is a multi-scale platform, allowing for the incorporation of functional nanoscale inks, the printing of microscale features, and ultimately the creation of macroscale devices. This blending of 3D printing, novel nanomaterial properties, and ‘living’ platforms may enable next-generation bionic systems. In this review, we highlight this synergistic integration of the unique properties of nanomaterials with the versatility of extrusion-based 3D printing technologies to interweave nanomaterials and fabricate novel bionic devices. PMID:27617026

The concept of the CCN protein family revisited: a centralized coordination network.

PubMed

Perbal, Bernard

2018-03-01

The wide array of biological properties attributed to the CCN family of proteins (Perbal in Lancet 363(9402):62-64, 2004) led me to reconsider the possible relationship and roles that these proteins may play as a team, instead of acting on their own as individual regulators in various signaling pathways. The dynamic model which I present in this review stems from the contribution of the biological properties that we established for CCN3, one of the three founding members of the CCN family, which was identified by our group as the first CCN protein showing growth inhibitory properties (1992), expressed mainly in quiescent cells (1996), and showing anti-tumor activities in several cellular models both ex vivo and in vivo. At the present time CCN3 is the only member of the family that has been reported to negatively act on the progression of the cell cycle. The unique dual localisation of CCN3 in the nucleus and outside cells, either at the membrane or in the extracellular matrix, that I first established in 1999, and that now appears to be shared by several other CCN proteins, is a unique essential feature which can no longer be ignored. Based on the structural and functional properties of CCN3, shared by most of the CCN family members, I propose an « all in one » concept in which CCN proteins are team members with specific functions that are aimed at the same goal. This model accounts both for the functional specificity of the various CCN proteins, their sequential and opposite or complementary effects in various biological context, and for the biological consequences of their physical interaction and biological cross-regulation.

"Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients".

PubMed

Pappas, Dimitrios A; Kremer, Joel M; Reed, George; Greenberg, Jeffrey D; Curtis, Jeffrey R

2014-04-01

Comparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA). CERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-α inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naïve and biologic experienced). The unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA.

Uncovering the Biology of Cancers in Adolescents and Young Adults

Cancer.gov

Evidence suggests that some adolescent and young adult cancers may have unique genetic and biological features. Researchers are trying to better understand the biology of these cancers in order to identify potential therapeutic targets.

Packaging biological cargoes in mesoporous materials: opportunities for drug delivery.

PubMed

Siefker, Justin; Karande, Pankaj; Coppens, Marc-Olivier

2014-11-01

Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants. Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments. The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed.

The Synthesis and Biological Characterization of Acetal-Free Mimics of the Tumor-Associated Carbohydrate Antigens.

PubMed

Sadraei, Seyed I; Reynolds, Michael R; Trant, John F

2017-01-01

Carcinomas express unique carbohydrates, known as tumor-associated carbohydrate antigens (TACAs), on their surface. These are potential targets for anticancer vaccines; however, to date, no such vaccine has reached the clinic. One factor that may complicate the success of this effort is the lability of the glycosidic bond. Acetal-free carbohydrates are analogues that lack the glycosidic linkage by replacing either the endo or exo oxygen with a methylene. This chapter summarizes the seminal syntheses of the mucin TACAs, provides an overview of common techniques for the synthesis of carbasugars and C-glycosides, reviews the syntheses published to date of acetal-free TACA analogues, and provides an overview of their observed biological activity. We conclude by offering a summation of the challenges remaining to the field biologically and the potential that acetal-free TACAs have of answering several basic questions in carbohydrate immunology. © 2017 Elsevier Inc. All rights reserved.

InFlo: a novel systems biology framework identifies cAMP-CREB1 axis as a key modulator of platinum resistance in ovarian cancer.

PubMed

Dimitrova, N; Nagaraj, A B; Razi, A; Singh, S; Kamalakaran, S; Banerjee, N; Joseph, P; Mankovich, A; Mittal, P; DiFeo, A; Varadan, V

2017-04-27

Characterizing the complex interplay of cellular processes in cancer would enable the discovery of key mechanisms underlying its development and progression. Published approaches to decipher driver mechanisms do not explicitly model tissue-specific changes in pathway networks and the regulatory disruptions related to genomic aberrations in cancers. We therefore developed InFlo, a novel systems biology approach for characterizing complex biological processes using a unique multidimensional framework integrating transcriptomic, genomic and/or epigenomic profiles for any given cancer sample. We show that InFlo robustly characterizes tissue-specific differences in activities of signalling networks on a genome scale using unique probabilistic models of molecular interactions on a per-sample basis. Using large-scale multi-omics cancer datasets, we show that InFlo exhibits higher sensitivity and specificity in detecting pathway networks associated with specific disease states when compared to published pathway network modelling approaches. Furthermore, InFlo's ability to infer the activity of unmeasured signalling network components was also validated using orthogonal gene expression signatures. We then evaluated multi-omics profiles of primary high-grade serous ovarian cancer tumours (N=357) to delineate mechanisms underlying resistance to frontline platinum-based chemotherapy. InFlo was the only algorithm to identify hyperactivation of the cAMP-CREB1 axis as a key mechanism associated with resistance to platinum-based therapy, a finding that we subsequently experimentally validated. We confirmed that inhibition of CREB1 phosphorylation potently sensitized resistant cells to platinum therapy and was effective in killing ovarian cancer stem cells that contribute to both platinum-resistance and tumour recurrence. Thus, we propose InFlo to be a scalable and widely applicable and robust integrative network modelling framework for the discovery of evidence-based biomarkers and therapeutic targets.

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

DOE PAGES

Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne; ...

2014-12-11

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

Disparate Proteome Responses of Pathogenic and Non-pathogenic Aspergilli to Human Serum Measured by Activity-Based Protein Profiling (ABPP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiedner, Susan D.; Ansong, Charles; Webb-Robertson, Bobbie-Jo M.

2013-07-01

Aspergillus fumigatus is the primary pathogen causing the devastating pulmonary disease Invasive Aspergillosis in immunocompromised individuals. Genomic analysis shows high synteny between A. fumigatus and closely related rarely pathogenic Neosartorya fischeri and Aspergillus clavatus genomes. To investigate the presence of unique or highly inducible protein reactivity in the pathogen, we applied activity-based protein profiling to compare protein reactivity of all three fungi over time in minimal media growth and in response to human serum. We found 350 probe-reactive proteins exclusive to A. fumigatus, including known virulence associated proteins, and 13 proteins associated with stress response exclusive to A. fumigatus culturemore » in serum. Though the fungi are highly orthologous, A. fumigatus has significantly more activity across varied biological process. Only 50% of expected orthologs of measured A. fumigatus reactive proteins were observed in N. fischeri and A. clavatus. Human serum induced processes uniquely or significantly represented in A. fumigatus include actin organization and assembly, transport, and fatty acid, cell membrane, and cell wall synthesis. Additionally, signaling proteins regulating vegetative growth, conidiation, and cell wall integrity, required for appropriate cellular response to external stimuli, had higher reactivity over time in A. fumigatus and N. fisheri, but not in A. clavatus. Together, we show that measured proteins and physiological processes identified solely or significantly over-represented in A. fumigatus reveal a unique adaptive response to human protein not found in closely related, but rarely aspergilli. These unique protein reactivity responses may reveal how A. fumigatus initiates pulmonary invasion leading to Invasive Aspergillosis.« less

Challenges and Opportunities for Learning Biology in Distance-Based Settings

ERIC Educational Resources Information Center

Hallyburton, Chad L.; Lunsford, Eddie

2013-01-01

The history of learning biology through distance education is documented. A review of terminology and unique problems associated with biology instruction is presented. Using published research and their own teaching experience, the authors present recommendations and best practices for managing biology in distance-based formats. They offer ideas…

Biological and genetic properties of the p53 null preneoplastic mammary epithelium

NASA Technical Reports Server (NTRS)

Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

2002-01-01

The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

Occurrence, Functions and Biological Significance of Arginine-Rich Proteins.

PubMed

Chandana, Thimmegowda; Venkatesh, Yeldur P

2016-01-01

Arginine, the most basic among the 20 amino acids, occurs less frequently than lysine in proteins despite being coded by six codons. Only a few important proteins of biological significance have been found to be abundant in arginine. It has been established that these arginine-rich proteins have been assigned important roles in the biological systems. Arginine-rich cationic proteins are known to stabilize macromolecular structures by establishing appropriate interactions (salt bridges, hydrogen bonds and cation-π interactions). These proteins are also known to be the key members of many regulatory pathways such as gene expression, chromatin stability, expurgation of introns from naïve mRNA, mRNA splicing, membrane-penetrating activity and pathogenesis-related defense, to name a few. Further, arginine occurs in various combinations with other amino acids (serine, lysine, proline, tryptophan, valine, glycine and glutamic acid) which diversify the potential functions of arginine-rich proteins. Arginine-rich proteins known till date from dietary sources have been described in terms of their structure and functional properties. A variety of activities such as bactericidal, membrane-penetrating, antimicrobial, anti-hypertensive, pro-angiogenic and others have been reported for arginine-rich proteins. This review attempts to collate the occurrence, functions and the biological significance of this unique class of proteins rich in arginine.

Synthesis of Single-walled Carbon Nanotubes Coated with Thiol-reactive Gel via Emulsion Polymerization.

PubMed

Nagai, Yukiko; Tsutsumi, Yusuke; Nakashima, Naotoshi; Fujigaya, Tsuyohiko

2018-06-15

Single-walled carbon nanotubes (SWNTs) have unique near-infrared absorption and photoemission properties that are attractive for in vivo biological applications such as photothermal cancer treatment and bioimaging. Therefore, a smart functionalization strategy for SWNTs to create biocompatible surfaces and introduce various ligands to target active cancer cells without losing the unique optical properties of the SWNTs is strongly desired. This paper reports the de-sign and synthesis of a SWNT/gel hybrid containing maleimide groups, which react with various thiol compounds through Michael addition reactions. In this hybrid, the method called carbon nanotube micelle polymerization was used to non-covalently modify the surface of SWNTs with a cross-linked polymer gel layer. This method can form an extremely stable gel layer on SWNTs; such stability is essential for in vivo biological applications. The monomer used to form the gel layer contained a maleimide group, which was protected with furan in endo-form. The resulting hybrid was treated in water to induce deprotection via retro Diels-Alder reaction and then functionalized with thiol com-pounds through Michael addition. The functionalization of the hybrid was explored using a thiol-containing fluores-cent dye as a model thiol and the formation of the SWNT-dye conjugate was confirmed by energy transfer from the dye to SWNTs. Our strategy offers a promising SWNT-based platform for biological functionalization for cancer targeting, imaging, and treatment.

Cognition and Culture in Evolutionary Context.

PubMed

Colmenares, Fernando; Hernández-Lloreda, María Victoria

2017-01-09

In humans and other animals, the individuals' ability to adapt efficiently and effectively to the niches they have actively contributed to construct relies heavily on an evolved psychology which has been shaped by biological, social, and cultural processes over evolutionary time. As expected, although many of the behavioral and cognitive components of this evolved psychology are widely shared across species, many others are species-unique. Although many animal species are known to acquire group-specific traditions (or cultures) via social learning, human culture is unique in terms of its contents and characteristics (observable and unobservable products, cumulative effects, norm conformity, and norm enforcement) and of its cognitive underpinnings (imitation, instructed teaching, and language). Here we provide a brief overview of some of the issues that are currently tackled in the field. We also highlight some of the strengths of a biological, comparative, non-anthropocentric and evolutionarily grounded approach to the study of culture. The main contributions of this approach to the science of culture are its emphasis (a) on the integration of information on mechanisms, function, and evolution, and on mechanistic factors located at different levels of the biological hierarchy, and (b) on the search for general principles that account for commonalities and differences between species, both in the cultural products and in the processes of innovation, dissemination, and accumulation involved that operate during developmental and evolutionary timespans.

Structure-function studies with the unique hexameric form II ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodopseudomonas palustris.

PubMed

Satagopan, Sriram; Chan, Sum; Perry, L Jeanne; Tabita, F Robert

2014-08-01

The first x-ray crystal structure has been solved for an activated transition-state analog-bound form II ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). This enzyme, from Rhodopseudomonas palustris, assembles as a unique hexamer with three pairs of catalytic large subunit homodimers around a central 3-fold symmetry axis. This oligomer arrangement is unique among all known Rubisco structures, including the form II homolog from Rhodospirillum rubrum. The presence of a transition-state analog in the active site locked the activated enzyme in a "closed" conformation and revealed the positions of critical active site residues during catalysis. Functional roles of two form II-specific residues (Ile(165) and Met(331)) near the active site were examined via site-directed mutagenesis. Substitutions at these residues affect function but not the ability of the enzyme to assemble. Random mutagenesis and suppressor selection in a Rubisco deletion strain of Rhodobacter capsulatus identified a residue in the amino terminus of one subunit (Ala(47)) that compensated for a negative change near the active site of a neighboring subunit. In addition, substitution of the native carboxyl-terminal sequence with the last few dissimilar residues from the related R. rubrum homolog increased the enzyme's kcat for carboxylation. However, replacement of a longer carboxyl-terminal sequence with termini from either a form III or a form I enzyme, which varied both in length and sequence, resulted in complete loss of function. From these studies, it is evident that a number of subtle interactions near the active site and the carboxyl terminus account for functional differences between the different forms of Rubiscos found in nature. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Neem (Azadirachta indica A. Juss) Oil to Tackle Enteropathogenic Escherichia coli

PubMed Central

Del Serrone, Paola; Nicoletti, Marcello

2015-01-01

Neem (Azadirachta indica A. Juss) oil (NO) was assayed against forty-eight isolates of Escherichia coli by standardised disc diffusion test and microdilution test. By molecular biology characterization, fourteen isolates resulted in diarrheagenic E. coli with sixteen primer pairs that specifically amplify unique sequences of virulence genes and of 16S rRNA. The NO showed biological activity against all isolates. The bacterial growth inhibition zone by disc diffusion method (100 µL NO) ranged between 9.50 ± 0.70 and 30.00 ± 1.00 mm. The antibacterial activity was furthermore determined at lower NO concentrations (1 : 10–1 : 10,000). The percent of growth reduction ranged between 23.71 ± 1.00 and 99.70 ± 1.53. The highest bacterial growth reduction was 1 : 10 NO concentration with 50 µL of bacterial suspension (ca. 1 × 106 CFU/mL). There is significant difference between the antibacterial activities against pathogenic and nonpathogenic E. coli, as well as NO and ciprofloxacin activities. Viable cells after the different NO concentration treatments were checked by molecular biology assay using PMA dye. On the basis of the obtained results, NO counteracts E. coli and also influences the virulence of E. coli viable cells after NO treatment. The NO metabolomic composition was obtained using fingerprint HPTLC. PMID:26064900

Neem (Azadirachta indica A. Juss) Oil to Tackle Enteropathogenic Escherichia coli.

PubMed

Del Serrone, Paola; Toniolo, Chiara; Nicoletti, Marcello

2015-01-01

Neem (Azadirachta indica A. Juss) oil (NO) was assayed against forty-eight isolates of Escherichia coli by standardised disc diffusion test and microdilution test. By molecular biology characterization, fourteen isolates resulted in diarrheagenic E. coli with sixteen primer pairs that specifically amplify unique sequences of virulence genes and of 16S rRNA. The NO showed biological activity against all isolates. The bacterial growth inhibition zone by disc diffusion method (100 µL NO) ranged between 9.50 ± 0.70 and 30.00 ± 1.00 mm. The antibacterial activity was furthermore determined at lower NO concentrations (1 : 10-1 : 10,000). The percent of growth reduction ranged between 23.71 ± 1.00 and 99.70 ± 1.53. The highest bacterial growth reduction was 1 : 10 NO concentration with 50 µL of bacterial suspension (ca. 1 × 10(6) CFU/mL). There is significant difference between the antibacterial activities against pathogenic and nonpathogenic E. coli, as well as NO and ciprofloxacin activities. Viable cells after the different NO concentration treatments were checked by molecular biology assay using PMA dye. On the basis of the obtained results, NO counteracts E. coli and also influences the virulence of E. coli viable cells after NO treatment. The NO metabolomic composition was obtained using fingerprint HPTLC.

Parallel single-cell analysis of active caspase-3/7 in apoptotic and non-apoptotic cells.

PubMed

Ledvina, Vojtěch; Janečková, Eva; Matalová, Eva; Klepárník, Karel

2017-01-01

Analysing the chemical content of individual cells has already been proven to reveal unique information on various biological processes. Single-cell analysis provides more accurate and reliable results for biology and medicine than analyses of extracts from cell populations, where a natural heterogeneity is averaged. To meet the requirements in the research of important biologically active molecules, such as caspases, we have developed a miniaturized device for simultaneous analyses of individual cells. A stainless steel body with a carousel holder enables high-sensitivity parallel detections in eight microvials. The holder is mounted in front of a photomultiplier tube with cooled photocathode working in photon counting mode. The detection of active caspase-3/7, central effector caspases in apoptosis, in single cells is based on the bioluminescence chemistry commercially available as Caspase-Glo ® 3/7 reagent developed by Promega. Individual cells were captured from a culture medium under microscope and transferred by micromanipulator into detection microvial filled with the reagent. As a result of testing, the limits of detection and quantification were determined to be 0.27/0.86 of active caspase-3/7 content in an average apoptotic cell and 0.46/2.92 for non-apoptotic cells. Application potential of this technology in laboratory diagnostics and related medical research is discussed. Graphical abstract Miniaturized device for simultaneous analyses of individual cells.

Nothing in Evolution Makes Sense Except in the Light of Genomics: Read-Write Genome Evolution as an Active Biological Process.

PubMed

Shapiro, James A

2016-06-08

The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess "Read-Write Genomes" they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification.

Nothing in Evolution Makes Sense Except in the Light of Genomics: Read–Write Genome Evolution as an Active Biological Process

PubMed Central

Shapiro, James A.

2016-01-01

The 21st century genomics-based analysis of evolutionary variation reveals a number of novel features impossible to predict when Dobzhansky and other evolutionary biologists formulated the neo-Darwinian Modern Synthesis in the middle of the last century. These include three distinct realms of cell evolution; symbiogenetic fusions forming eukaryotic cells with multiple genome compartments; horizontal organelle, virus and DNA transfers; functional organization of proteins as systems of interacting domains subject to rapid evolution by exon shuffling and exonization; distributed genome networks integrated by mobile repetitive regulatory signals; and regulation of multicellular development by non-coding lncRNAs containing repetitive sequence components. Rather than single gene traits, all phenotypes involve coordinated activity by multiple interacting cell molecules. Genomes contain abundant and functional repetitive components in addition to the unique coding sequences envisaged in the early days of molecular biology. Combinatorial coding, plus the biochemical abilities cells possess to rearrange DNA molecules, constitute a powerful toolbox for adaptive genome rewriting. That is, cells possess “Read–Write Genomes” they alter by numerous biochemical processes capable of rapidly restructuring cellular DNA molecules. Rather than viewing genome evolution as a series of accidental modifications, we can now study it as a complex biological process of active self-modification. PMID:27338490

Detection and Quantification of Biologically Active Botulinum Neurotoxin Serotypes A and B Using a Förster Resonance Energy Transfer-Based Quantum Dot Nanobiosensor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yun; Fry, H. Christopher; Skinner, Guy E.

Botulinum neurotoxin (BoNT) is the most potent toxin known. The ingestion of food contaminated with biologically active BoNT causes foodborne botulism, which can lead to respiratory paralysis, coma, and death after ingestion of as little as 70 mu g for a 70 kg human. Because of its lethality and challenges associated with current detection methods, there is an urgent need for highly sensitive rapid screening techniques capable of detecting biologically active BoNT. Here, we describe a Forster resonance energy transfer-based nanobiosensor that uses quantum dots (QDs) and two specific quencher-labeled peptide probes to detect and differentiate two biologically active formsmore » of BoNT, serotypes A and B, which were responsible for 80% of human foodborne botulism cases in the U.S. from 2012 to 2015. Each peptide probe contains an enzymatic cleavage site specific to only one serotype. QDs were selected based on the spectral overlap with the quenchers. In the presence of the target BoNT serotype, the peptide probe is cleaved and the quenching of QD photoluminescence (PL) is reduced, giving a signal that is easily detected by a PL spectrophotometer. This sensor performance was evaluated with light chains of BoNT/A and BoNT/B (LcA and LcB), catalytic domains of the respective serotypes. LcA and LcB were detected in 3 h with limits of detection of 0.2 and 2 ng/mL, respectively. The specificity of the sensor was evaluated, and no cross-reactivity from nontarget serotypes was observed with 2 h of incubation. Because each serotype-specific peptide is conjugated to a QD with a unique emission wavelength, multiple biologically active BoNT serotypes could be detected in one PL spectrum. The sensor was also shown to be responsive to BoNT/A and BoNT/B holotoxins. Good performance of this sensor implies its potential application as a rapid screening method for biologically active BoNT/A and BoNT/B in the laboratory and in the field.« less

Art and brain: insights from neuropsychology, biology and evolution.

PubMed

Zaidel, Dahlia W

2010-02-01

Art is a uniquely human activity associated fundamentally with symbolic and abstract cognition. Its practice in human societies throughout the world, coupled with seeming non-functionality, has led to three major brain theories of art. (1) The localized brain regions and pathways theory links art to multiple neural regions. (2) The display of art and its aesthetics theory is tied to the biological motivation of courtship signals and mate selection strategies in animals. (3) The evolutionary theory links the symbolic nature of art to critical pivotal brain changes in Homo sapiens supporting increased development of language and hierarchical social grouping. Collectively, these theories point to art as a multi-process cognition dependent on diverse brain regions and on redundancy in art-related functional representation.

Art and brain: insights from neuropsychology, biology and evolution

PubMed Central

Zaidel, Dahlia W

2010-01-01

Art is a uniquely human activity associated fundamentally with symbolic and abstract cognition. Its practice in human societies throughout the world, coupled with seeming non-functionality, has led to three major brain theories of art. (1) The localized brain regions and pathways theory links art to multiple neural regions. (2) The display of art and its aesthetics theory is tied to the biological motivation of courtship signals and mate selection strategies in animals. (3) The evolutionary theory links the symbolic nature of art to critical pivotal brain changes in Homo sapiens supporting increased development of language and hierarchical social grouping. Collectively, these theories point to art as a multi-process cognition dependent on diverse brain regions and on redundancy in art-related functional representation. PMID:19490399

Mechanical properties of biological specimens explored by atomic force microscopy

NASA Astrophysics Data System (ADS)

Kasas, S.; Longo, G.; Dietler, G.

2013-04-01

The atomic force microscope is a widely used surface scanning apparatus capable of reconstructing at a nanometric scale resolution the 3D morphology of biological samples. Due to its unique sensitivity, it is now increasingly used as a force sensor, to characterize the mechanical properties of specimens with a similar lateral resolution. This unique capability has produced, in the last years, a vast increase in the number of groups that have exploited the versatility and sensitivity of the instrument to explore the nanomechanics of various samples in the fields of biology, microbiology and medicine. In this review we outline the state of the art in this field, reporting the most interesting recent works involving the exploration of the nanomechanical properties of various biological samples.

IFN-λ: A New Inducer of Local Immunity against Cancer and Infections

PubMed Central

Lasfar, Ahmed; Zloza, Andrew; de la Torre, Andrew; Cohen-Solal, Karine A.

2016-01-01

IFN-λ is the newly established type III IFN with unique immunomodulatory functions. In contrast to the IFN-α/β family and to some extent IFN-γ, IFN-λ is apparently acting in specific areas of the body to activate resident immune cells and induces a local immunity, instrumental in preventing particular infections and also keeping transformed cells under control. Mucosal areas of lung and gastrointestinal tracts are now under scrutiny to elucidate the immune mechanisms triggered by IFN-λ and leading to viral protection. New evidence also indicates the crucial role of IFN-λ in promoting innate immunity in solid cancer models. Based on its unique biological activities among the IFN system, new immunotherapeutic approaches are now emerging for the treatment of cancer, infection, and autoimmune diseases. In the present review, we highlight the recent advances of IFN-λ immunomodulatory functions. We also discuss the perspectives of IFN-λ as a therapeutic agent. PMID:28018361

Understanding disgust.

PubMed

Chapman, Hanah A; Anderson, Adam K

2012-03-01

Disgust is characterized by a remarkably diverse set of stimulus triggers, ranging from extremely concrete (bad tastes and disease vectors) to extremely abstract (moral transgressions and those who commit them). This diversity may reflect an expansion of the role of disgust over evolutionary time, from an origin in defending the body against toxicity and disease, through defense against other threats to biological fitness (e.g., incest), to involvement in the selection of suitable interaction partners, by motivating the rejection of individuals who violate social and moral norms. The anterior insula, and to a lesser extent the basal ganglia, are implicated in toxicity- and disease-related forms of disgust, although we argue that insular activation is not exclusive to disgust. It remains unclear whether moral disgust is associated with insular activity. Disgust offers cognitive neuroscientists a unique opportunity to study how an evolutionarily ancient response rooted in the chemical senses has expanded into a uniquely human social cognitive domain; many interesting research avenues remain to be explored. © 2012 New York Academy of Sciences.

Rain pulse response of soil CO2 exchange by biological soil crusts and grasslands of the semiarid Colorado Plateau, United States

USGS Publications Warehouse

Bowling, David R.; Grote, E.E.; Belnap, J.

2011-01-01

Biological activity in arid grasslands is strongly dependent on moisture. We examined gas exchange of biological soil crusts (biocrusts), the underlying soil biotic community, and the belowground respiratory activity of C3 and C4 grasses over 2 years in southeast Utah, USA. We used soil surface CO2 flux and the amount and carbon isotope composition (δ13C) of soil CO2 as indicators of belowground and soil surface activity. Soil respiration was always below 2 μmol m-2s-1 and highly responsive to soil moisture. When moisture was available, warm spring and summer temperature was associated with higher fluxes. Moisture pulses led to enhanced soil respiration lasting for a week or more. Biological response to rain was not simply dependent on the amount of rain, but also depended on antecedent conditions (prior moisture pulses). The short-term temperature sensitivity of respiration was very dynamic, showing enhancement within 1-2 days of rain, and diminishing each day afterward. Carbon uptake occurred by cyanobacterially dominated biocrusts following moisture pulses in fall and winter, with a maximal net carbon uptake of 0.5 μmol m-2s-1, although typically the biocrusts were a net carbon source. No difference was detected in the seasonal activity of C3 and C4 grasses, contrasting with studies from other arid regions (where warm- versus cool-season activity is important), and highlighting the unique biophysical environment of this cold desert. Contrary to other studies, the δ13C of belowground respiration in the rooting zone of each photosynthetic type did not reflect the δ13C of C3 and C4 physiology.

Sex Hormone Effects on Physical Activity Levels: Why Doesn’t Jane Run as Much as Dick?

PubMed Central

Bowen, Robert S.; Turner, Michael J.; Lightfoot, J. Timothy

2010-01-01

The relationship between physical activity levels and disease rates have become an important health related concern in the developed world. Heart disease, certain cancers, and obesity persist at epidemic rates in the United States and Western Europe. Increased physical activity levels have been shown to reduce the occurrence of many chronic diseases leading to reductions in the burden on the health care system. Activity levels in humans are affected by many cultural and environmental factors, nevertheless current research points to a strong biological input with potential genetic, neurological, and endocrinological origins. Of unique interest, the sex hormones appear to have a very strong influence on activity levels. The current animal literature suggests that females tend to be more active than males due to biological pathways of estrogenic origin. The majority of human epidemiological and anthropological data, on the contrary, suggest women are less active than men in spite of this inherent activity-increasing mechanism. The purpose of this manuscript was to review the current literature regarding the control of physical activity levels by the sex hormones in humans. Using the natural transitional phases of the aging endocrine system, natural periodicity of the menstrual cycle, and pharmacological/hormone replacement therapy as variable experimental stages, some authors have been able to provide some information regarding the existence of an inherent activity-increasing mechanism in humans. In brief, activity levels during life stages prior to and after menopause do not significantly differ, despite the vast changes in sex hormone levels and function. Activity difference throughout a regular menstrual cycle do not appear to influence activity levels in humans either—an effect that is pronounced in the female rodent. The use of hormone replacement therapies provide researchers with more systematic controls over hormone modulation in human subjects; however, this benefit comes with additional confounding variables, mostly due to disease or other states of malfunction. Despite the addition of these confounding factors, minor changes to the activity pattern have been observed in women, especially during the initial administration for the therapy. Observations are yet to be made in male subjects during replacement therapy. In general, some evidence exists suggesting that a biological mechanism—extending from the sex hormones—influences activity in humans. Unfortunately, despite a small number of investigative reports, the paucity of human research investigating how the sex hormones affect activity levels in humans prevents conclusive delineation of the mechanisms involved. Future research in this unique sub-field of endocrinology and exercise science utilizing more appropriate research protocols and effective techniques will provide definitive evidence of such mechanisms. PMID:21142285

Opportunities and questions for the fundamental biological sciences in space

NASA Technical Reports Server (NTRS)

Sharp, Joseph C.; Vernikos, Joan

1993-01-01

With the advent of sophisticated space facilities we discuss the overall nature of some biological questions that can be addressed. We point out the need for broad participation by the biological community, the necessary facilities, and some unique requirements.

Tocotrienols: The lesser known form of natural vitamin E

PubMed Central

Patel, Viren; Rink, Cameron; Khanna, Savita; Sen, Chandan K

2014-01-01

A recent and growing body of research has shown that members of this vitamin E family posses unique biologic functions. Tocotrienols have garnered much of this recent attention, and in particular α-tocotrienol has been shown to be the most potent neuroprotective form of vitamin E. Protection exclusively mediated through tocotrienols has been arbitrated to many mechanisms including inhibition of 12-LOX, c-Src, PLA2 and through up-regulation of MRP1. Further, tocotrienols have recently been shown to induce arteriogenesis through induction of TIMP1 and decreased activation of MMP2. However, the unique therapeutic potential of tocotrienols is not limited to neuroprotection. Tocotrienols have been shown to have molecular targets including: apoptotic regulators, cytokines, adhesion molecules, enzymes, kinases, receptors, transcription factors, and growth factors. In spite of this large and unique therapeutic potential, scientific literature on tocotrienols only accounts for approximately 1% of vitamin E research. Given the potential of tocotrienols and relatively scant literature, further investigation is warranted. PMID:22013739

Structure and function of polyketide biosynthetic enzymes: various strategies for production of structurally diverse polyketides.

PubMed

Miyanaga, Akimasa

2017-12-01

Polyketides constitute a large family of natural products that display various biological activities. Polyketides exhibit a high degree of structural diversity, although they are synthesized from simple acyl building blocks. Recent biochemical and structural studies provide a better understanding of the biosynthetic logic of polyketide diversity. This review highlights the biosynthetic mechanisms of structurally unique polyketides, β-amino acid-containing macrolactams, enterocin, and phenolic lipids. Functional and structural studies of macrolactam biosynthetic enzymes have revealed the unique biosynthetic machinery used for selective incorporation of a rare β-amino acid starter unit into the polyketide skeleton. Biochemical and structural studies of cyclization enzymes involved in the biosynthesis of enterocin and phenolic lipids provide mechanistic insights into how these enzymes diversify the carbon skeletons of their products.

Secondary Metabolites from Polar Organisms

PubMed Central

Tian, Yuan; Li, Yan-Ling; Zhao, Feng-Chun

2017-01-01

Polar organisms have been found to develop unique defences against the extreme environment environment, leading to the biosynthesis of novel molecules with diverse bioactivities. This review covers the 219 novel natural products described since 2001, from the Arctic and the Antarctic microoganisms, lichen, moss and marine faunas. The structures of the new compounds and details of the source organism, along with any relevant biological activities are presented. Where reported, synthetic and biosynthetic studies on the polar metabolites have also been included. PMID:28241505

Understanding DNA replication by the bacteriophage T4 replisome.

PubMed

Benkovic, Stephen J; Spiering, Michelle M

2017-11-10

The T4 replisome has provided a unique opportunity to investigate the intricacies of DNA replication. We present a comprehensive review of this system focusing on the following: its 8-protein composition, their individual and synergistic activities, and assembly in vitro and in vivo into a replisome capable of coordinated leading/lagging strand DNA synthesis. We conclude with a brief comparison with other replisomes with emphasis on how coordinated DNA replication is achieved. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Leishmania Surveillance and Diagnostic Capability in Support of the Joint Biological Agent Identification and Diagnostic System (JBAIDS) and Leishmania Vector Surveillance

DTIC Science & Technology

2013-02-07

specific biosurveillance activities as well as clinical applications and alternative versions preformatted and categorized as ‘high-tech’ and ‘low-tech’ and...methodologies. Application for patent protection of this DoD intellectual property is underway. 1::1 . :::.u~~l-1 I ~111VI:::O Leishmaniasis...LHL assay and the need to develop novel and unique sample preparation methodologies. Application for patent protection of this DoD intellectual

Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis.

PubMed

Martinez, Luis; Thames, Easter; Kim, Jinna; Chaudhuri, Gautam; Singh, Rajan; Pervin, Shehla

2016-07-29

Breast cancer is a complex heterogeneous disease where many distinct subtypes are found. Younger African American (AA) women often present themselves with aggressive form of breast cancer with unique biology which is very difficult to treat. Better understanding the biology of AA breast tumors could lead to development of effective treatment strategies. Our previous studies indicate that AA but not Caucasian (CA) triple negative (TN) breast cancer cells were sensitive to nitrosative stress-induced cell death. In this study, we elucidate possible mechanisms that contribute to nitric oxide (NO)-induced apoptosis in AA TN breast cancer cells. Breast cancer cells were treated with various concentrations of long-acting NO donor, DETA-NONOate and cell viability was determined by trypan blue exclusion assay. Apoptosis was determined by TUNEL and caspase 3 activity as well as changes in mitochondrial membrane potential. Caspase 3 and Bax cleavage, levels of Cu/Zn superoxide dismutase (SOD) and Mn SOD was assessed by immunoblot analysis. Inhibition of Bax cleavage by Calpain inhibitor, and levels of reactive oxygen species (ROS) as well as SOD activity was measured in NO-induced apoptosis. In vitro and in vivo effect of NO treatment on mammary cancer stem cells (MCSCs) was assessed. NO induced mitocondria-mediated apoptosis in all AA but not in CA TN breast cancer cells. We found significant TUNEL-positive cells, cleavage of Bax and caspase-3 activation as well as depolarization mitochondrial membrane potential only in AA TN breast cancer cells exposed to NO. Inhibition of Bax cleavage and quenching of ROS partially inhibited NO-induced apoptosis in AA TN cells. Increase in ROS coincided with reduction in SOD activity in AA TN breast cancer cells. Furthermore, NO treatment of AA TN breast cancer cells dramatically reduced aldehyde dehydrogenase1 (ALDH1) expressing MCSCs and xenograft formation but not in breast cancer cells from CA origin. Ethnic differences in breast tumors dictate a need for tailoring treatment options more suited to the unique biology of the disease.

The Ozark Highlands

USGS Publications Warehouse

Ethridge, Max

2009-01-01

The Ozark Highlands include diverse topographic, geologic, soil, and hydrologic conditions that support a broad range of habitat types. The landscape features rugged uplands - some peaks higher than 2,500 feet above sea level - with exposed rock and varying soil depths and includes extensive areas of karst terrain. The Highlands are characterized by extreme biological diversity and high endemism (uniqueness of species). Vegetation communities are dominated by open oak-hickory and shortleaf pine woodlands and forests. Included in this vegetation matrix is an assemblage of various types of fens, forests, wetlands, fluvial features, and carbonate and siliceous glades. An ever-growing human population in the Ozark Highlands has become very dependent on reservoirs constructed on major rivers in the region and, in some cases, groundwater for household and public water supply. Because of human population growth in the Highlands and increases in industrial and agricultural activities, not only is adequate water quantity an issue, but maintaining good water quality is also a challenge. Point and nonpoint sources of excessive nutrients are an issue. U.S. Geological Survey (USGS) partnership programs to monitor water quality and develop simulation tools to help stakeholders better understand strategies to protect the quality of water and the environment are extremely important. The USGS collects relevant data, conducts interpretive studies, and develops simulation tools to help stakeholders understand resource availability and sustainability issues. Stakeholders dependent on these resources are interested in and benefit greatly from evolving these simulation tools (models) into decision support systems that can be used for adaptive management of water and ecological resources. The interaction of unique and high-quality biological and hydrologic resources and the effects of stresses from human activities can be evaluated best by using a multidisciplinary approach that the USGS can provide. Information varying from defining baseline resource conditions to developing simulation models will help resource managers and users understand the human impact on resource sustainability. Varied expertise and experience in biological and water-resources activities across the entire Highlands make the USGS a valued collaborator in studies of Ozark ecosystems, streams, reservoirs, and groundwater. A large part of future success will depend on the involvement and active participation of key partners.

Development and biological applications of optical tweezers and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Xie, Chang'an

Optical tweezers is a three-dimensional manipulation tool that employs a gradient force that originates from the single highly focused laser beam. Raman spectroscopy is a molecular analytical tool that can give a highly unique "fingerprint" for each substance by measuring the unique vibrations of its molecules. The combination of these two optical techniques offers a new tool for the manipulation and identification of single biological cells and microscopic particles. In this thesis, we designed and implemented a Laser-Tweezers-Raman-Spectroscopy (LTRS) system, also called the Raman-tweezers, for the simultaneous capture and analysis of both biological particles and non-biological particles. We show that microparticles can be conveniently captured at the focus of a laser beam and the Raman spectra of trapped particles can be acquired with high quality. The LTRS system overcomes the intrinsic Brownian motion and cell motility of microparticles in solution and provides a promising tool for in situ identifying suspicious agents. In order to increase the signal to noise ratio, several schemes were employed in LTRS system to reduce the blank noise and the fluorescence signal coming from analytes and the surrounding background. These techniques include near-infrared excitation, optical levitation, confocal microscopy, and frequency-shifted Raman difference. The LTRS system has been applied for the study in cell biology at the single cell level. With the built Raman-tweezers system, we studied the dynamic physiological processes of single living cells, including cell cycle, the transcription and translation of recombinant protein in transgenic yeast cells and the T cell activation. We also studied cell damage and associated biochemical processes in optical traps, UV radiations, and evaluated heating by near-infrared Raman spectroscopy. These studies show that the Raman-tweezers system is feasible to provide rapid and reliable diagnosis of cellular disorders and can be used as a valuable tool to study cellular processes within single living cells or intracellular organelles and may aid research in molecular and cellular biology.

Bioinspired Functional Surfaces for Technological Applications

NASA Astrophysics Data System (ADS)

Sharma, Vipul; Kumar, Suneel; Reddy, Kumbam Lingeshwar; Bahuguna, Ashish; Krishnan, Venkata

2016-08-01

Biological matters have been in continuous encounter with extreme environmental conditions leading to their evolution over millions of years. The fittest have survived through continuous evolution, an ongoing process. Biological surfaces are the important active interfaces between biological matters and the environment, and have been evolving over time to a higher state of intelligent functionality. Bioinspired surfaces with special functionalities have grabbed attention in materials research in the recent times. The microstructures and mechanisms behind these functional biological surfaces with interesting properties have inspired scientists to create artificial materials and surfaces which possess the properties equivalent to their counterparts. In this review, we have described the interplay between unique multiscale (micro- and nano-scale) structures of biological surfaces with intrinsic material properties which have inspired researchers to achieve the desired wettability and functionalities. Inspired by naturally occurring surfaces, researchers have designed and fabricated novel interfacial materials with versatile functionalities and wettability, such as superantiwetting surfaces (superhydrophobic and superoleophobic), omniphobic, switching wettability and water collecting surfaces. These strategies collectively enable functional surfaces to be utilized in different applications such as fog harvesting, surface-enhanced Raman spectroscopy (SERS), catalysis, sensing and biological applications. This paper delivers a critical review of such inspiring biological surfaces and artificial bioinspired surfaces utilized in different applications, where material science and engineering have merged by taking inspiration from the natural systems.

From Extremophiles to Star Trek, The Use of Synthetic Biology in Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.; Fujishima, Kosuke; Lima, Ivan Paulino; Gentry, Diana; Phan, Samson; Navarette, Jesica; Palmer, Jesse; Burnier, Andre

2012-01-01

Synthetic biology – the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes – has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving biotic functions using only the most thermodynamically stable amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as bio-mining, human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Dibenzylbutyrolactone Lignans - A Review of Their Structural Diversity, Biosynthesis, Occurrence, Identification and Importance.

PubMed

Solyomváry, Anna; Beni, Szabolcs; Boldizsar, Imre

2017-01-01

Dibenzylbutyrolactone lignans represent a unique group of plant secondary metabolites with increasing significance in medicine. This review summarizes their structural characteristics and classification, as well as the biosynthesis starting in the chloroplast, and their supposed biological activity associated with plant defense mechanisms are also discussed. Over 85 natural dibenzylbutyrolactone lignans known to date and their corresponding plant sources are summarized herein for the first time, highlighting a taxon- and organ-specific accumulation of these compounds. The isolation strategies, applied analytical methods and pharmacological activities of dibenzylbutyrolactone lignans are also thoroughly reviewed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides

PubMed Central

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-01-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

PubMed

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-05-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. © The Author 2016. Published by Oxford University Press.

A Biological Condition Gradient Model for Historical Assessment of Estuarine Habitat Structure

EPA Science Inventory

Coastal ecosystems are affected by ever increasing natural and human pressures. Because the physical, chemical, and biological characteristics unique to each ecosystem control the ways that biological resources respond to ecosystem stressors, we recommend a flexible and adaptable...

Recombination and Population Mosaic of a Multifunctional Viral Gene, Adeno-Associated Virus cap

PubMed Central

Takeuchi, Yasuhiro; Myers, Richard; Danos, Olivier

2008-01-01

Homologous recombination is a dominant force in evolution and results in genetic mosaics. To detect evidence of recombination events and assess the biological significance of genetic mosaics, genome sequences for various viral populations of reasonably large size are now available in the GenBank. We studied a multi-functional viral gene, the adeno-associated virus (AAV) cap gene, which codes for three capsid proteins, VP1, VP2 and VP3. VP1-3 share a common C-terminal domain corresponding to VP3, which forms the viral core structure, while the VP1 unique N-terminal part contains an enzymatic domain with phospholipase A2 activity. Our recombinant detection program (RecI) revealed five novel recombination events, four of which have their cross-over points in the N-terminal, VP1 and VP2 unique region. Comparison of phylogenetic trees for different cap gene regions confirmed discordant phylogenies for the recombinant sequences. Furthermore, differences in the phylogenetic tree structures for the VP1 unique (VP1u) region and the rest of cap highlighted the mosaic nature of cap gene in the AAV population: two dominant forms of VP1u sequences were identified and these forms are linked to diverse sequences in the rest of cap gene. This observation together with the finding of frequent recombination in the VP1 and 2 unique regions suggests that this region is a recombination hot spot. Recombination events in this region preserve protein blocks of distinctive functions and contribute to convergence in VP1u and divergence of the rest of cap. Additionally the possible biological significance of two dominant VP1u forms is inferred. PMID:18286191

Characterization of actin filament deformation in response to actively driven microspheres propagated through entangled actin networks

NASA Astrophysics Data System (ADS)

Falzone, Tobias; Blair, Savanna; Robertson-Anderson, Rae

2014-03-01

The semi-flexible biopolymer actin is a ubiquitous component of nearly all biological organisms, playing an important role in many biological processes such as cell structure and motility, cancer invasion and metastasis, muscle contraction, and cell signaling. Concentrated actin networks possess unique viscoelastic properties that have been the subject of much theoretical and experimental work. However, much is still unknown regarding the correlation of the applied stress on the network to the induced filament strain at the molecular level. Here, we use dual optical traps alongside fluorescence microscopy to carry out active microrheology measurements that link mechanical stress to structural response at the micron scale. Specifically, we actively drive microspheres through entangled actin networks while simultaneously measuring the force the surrounding filaments exert on the sphere and visualizing the deformation and subsequent relaxation of fluorescent labeled filaments within the network. These measurements, which provide much needed insight into the link between stress and strain in actin networks, are critical for clarifying our theoretical understanding of the complex viscoelastic behavior exhibited in actin networks.

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

PubMed

Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

Dual Causality and the Autonomy of Biology.

PubMed

Bock, Walter J

2017-03-01

Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.

Whipworm kinomes reflect a unique biology and adaptation to the host animal.

PubMed

Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Chang, Bill C H; Nejsum, Peter; Pozio, Edoardo; La Rosa, Giuseppe; Sternberg, Paul W; Gasser, Robin B

2017-11-01

Roundworms belong to a diverse phylum (Nematoda) which is comprised of many parasitic species including whipworms (genus Trichuris). These worms have adapted to a biological niche within the host and exhibit unique morphological characteristics compared with other nematodes. Although these adaptations are known, the underlying molecular mechanisms remain elusive. The availability of genomes and transcriptomes of some whipworms now enables detailed studies of their molecular biology. Here, we defined and curated the full complement of an important class of enzymes, the protein kinases (kinomes) of two species of Trichuris, using an advanced and integrated bioinformatic pipeline. We investigated the transcription of Trichuris suis kinase genes across developmental stages, sexes and tissues, and reveal that selectively transcribed genes can be linked to central roles in developmental and reproductive processes. We also classified and functionally annotated the curated kinomes by integrating evidence from structural modelling and pathway analyses, and compared them with other curated kinomes of phylogenetically diverse nematode species. Our findings suggest unique adaptations in signalling processes governing worm morphology and biology, and provide an important resource that should facilitate experimental investigations of kinases and the biology of signalling pathways in nematodes. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Hydrodynamic Interactions in Active and Passive Matter

NASA Astrophysics Data System (ADS)

Krafnick, Ryan C.

Active matter is present at all biological length scales, from molecular apparatuses interior to cells, to swimming microscopic organisms, to birds, fish, and people. Its properties are varied and its applications diverse, but our understanding of the fundamental driving forces of systems with these constituents remains incomplete. This thesis examines active matter suspensions, exploring the role of hydrodynamic interactions on the unique and emergent properties therein. Both qualitative and quantitative impacts are considered, and care is taken in determining the physical origin of the results in question. It is found that fluid dynamical interactions are fundamentally, qualitatively important, and much of the properties of a system can be explained with an effective energy density defined via the fluid fields arising from the embedded self-propelling entities themselves.

Conceptions of the Nature of Biology Held by Senior Secondary School Biology Teachers in Ilorin, Kwara State, Nigeria

ERIC Educational Resources Information Center

Adegboye, Motunrayo Catherine; Bello, Ganiyu; Abimbola, Isaac O.

2017-01-01

There is a sustained public outcry against the persistent abysmal performance of students in biology and other science subjects at the Senior School Certificate Examinations conducted by the West African Examinations Council (WAEC) and the National Examinations Council (NECO). Biology is a unique science discipline with peculiar philosophical…

Explorations: A Research-Based Program Introducing Undergraduates to Diverse Biology Research Topics Taught by Grad Students and Postdocs

ERIC Educational Resources Information Center

Brownell, Sara E.; Khalfan, Waheeda; Bergmann, Dominique; Simoni, Robert

2013-01-01

Undergraduate biology majors are often overwhelmed by and underinformed about the diversity and complexity of biological research that is conducted on research-intensive campuses. We present a program that introduces undergraduates to the diversity and scope of biological research and also provides unique teaching opportunities for graduate…

Making Research Fly in Schools: "Drosophila" as a Powerful Modern Tool for Teaching Biology

ERIC Educational Resources Information Center

Harbottle, Jennifer; Strangward, Patrick; Alnuamaani, Catherine; Lawes, Surita; Patel, Sanjai; Prokop, Andreas

2016-01-01

The "droso4schools" project aims to introduce the fruit fly "Drosophila" as a powerful modern teaching tool to convey curriculum-relevant specifications in biology lessons. Flies are easy and cheap to breed and have been at the forefront of biology research for a century, providing unique conceptual understanding of biology and…

Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans

PubMed Central

Bottari, Davide; Troje, Nikolaus F.; Ley, Pia; Hense, Marlene; Kekunnaya, Ramesh; Röder, Brigitte

2016-01-01

Functional brain development is characterized by sensitive periods during which experience must be available to allow for the full development of neural circuits and associated behavior. Yet, only few neural markers of sensitive period plasticity in humans are known. Here we employed electroencephalographic recordings in a unique sample of twelve humans who had been blind from birth and regained sight through cataract surgery between four months and 16 years of age. Two additional control groups were tested: a group of visually impaired individuals without a history of total congenital blindness and a group of typically sighted individuals. The EEG was recorded while participants performed a visual discrimination task involving intact and scrambled biological motion stimuli. Posterior alpha and theta oscillations were evaluated. The three groups showed indistinguishable behavioral performance and in all groups evoked theta activity varied with biological motion processing. By contrast, alpha oscillatory activity was significantly reduced only in individuals with a history of congenital cataracts. These data document on the one hand brain mechanisms of functional recovery (related to theta oscillations) and on the other hand, for the first time, a sensitive period for the development of alpha oscillatory activity in humans. PMID:27080158

Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.

Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand–binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolutionmore » X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligand–binding site interactions are possibly responsible for their potent activity.« less

“Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients”

PubMed Central

2014-01-01

Background Comparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA). Methods/Design CERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-α inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naïve and biologic experienced). Discussion The unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA. PMID:24690143

The quantitative assessment of motor activity in mania and schizophrenia

PubMed Central

Minassian, Arpi; Henry, Brook L.; Geyer, Mark A.; Paulus, Martin P.; Young, Jared W.; Perry, William

2009-01-01

Background Increased motor activity is a cardinal feature of the mania of Bipolar Disorder (BD), and is thought to reflect dopaminergic dysregulation. Motor activity in BD has been studied almost exclusively with self-report and observer-rated scales, limiting the ability to objectively quantify this behavior. We used an ambulatory monitoring device to quantify motor activity in BD and schizophrenia (SCZ) patients in a novel exploratory paradigm, the human Behavioral Pattern Monitor (BPM). Method 28 patients in the manic phase of BD, 17 SCZ patients, and 21 nonpatient (NC) subjects were tested in the BPM, an unfamiliar room containing novel objects. Motor activity was measured with a wearable ambulatory monitoring device (LifeShirt). Results Manic BD patients exhibited higher levels of motor activity when exploring the novel environment than SCZ and NC groups. Motor activity showed some modest relationships with symptom ratings of mania and psychosis and was not related to smoking or body mass index. Limitations Although motor activity did not appear to be impacted significantly by antipsychotic or mood-stabilizing medications, this was a naturalistic study and medications were not controlled, thus limiting conclusions about potential medication effects on motor activity. Conclusion Manic BD patients exhibit a unique signature of motoric overactivity in a novel exploratory environment. The use of an objective method to quantify exploration and motor activity may help characterize the unique aspects of BD and, because it is amenable to translational research, may further the study of the biological and genetic bases of the disease. PMID:19435640

The quantitative assessment of motor activity in mania and schizophrenia.

PubMed

Minassian, Arpi; Henry, Brook L; Geyer, Mark A; Paulus, Martin P; Young, Jared W; Perry, William

2010-01-01

Increased motor activity is a cardinal feature of the mania of Bipolar Disorder (BD), and is thought to reflect dopaminergic dysregulation. Motor activity in BD has been studied almost exclusively with self-report and observer-rated scales, limiting the ability to objectively quantify this behavior. We used an ambulatory monitoring device to quantify motor activity in BD and schizophrenia (SCZ) patients in a novel exploratory paradigm, the human Behavioral Pattern Monitor (BPM). 28 patients in the manic phase of BD, 17 SCZ patients, and 21 nonpatient (NC) subjects were tested in the BPM, an unfamiliar room containing novel objects. Motor activity was measured with a wearable ambulatory monitoring device (LifeShirt). Manic BD patients exhibited higher levels of motor activity when exploring the novel environment than SCZ and NC groups. Motor activity showed some modest relationships with symptom ratings of mania and psychosis and was not related to smoking or body mass index. Although motor activity did not appear to be impacted significantly by antipsychotic or mood-stabilizing medications, this was a naturalistic study and medications were not controlled, thus limiting conclusions about potential medication effects on motor activity. Manic BD patients exhibit a unique signature of motoric overactivity in a novel exploratory environment. The use of an objective method to quantify exploration and motor activity may help characterize the unique aspects of BD and, because it is amenable to translational research, may further the study of the biological and genetic bases of the disease.

Phosphodiesterase type 5 and cancers: progress and challenges

PubMed Central

Barone, Ines; Giordano, Cinzia; Bonofiglio, Daniela; Andò, Sebastiano; Catalano, Stefania

2017-01-01

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. In this review, we present an overview of the experimental and clinical evidences highlighting the role of PDE5 in the pathogenesis and prevention of various malignancies. Current data are still not sufficient to draw conclusive statements for cancer patient management, but could provide further rational for testing PDE5-targeting drugs as anticancer agents in clinical settings. PMID:29228762

Studying mechanism of radical reactions: From radiation to nitroxides as research tools

NASA Astrophysics Data System (ADS)

Maimon, Eric; Samuni, Uri; Goldstein, Sara

2018-02-01

Radicals are part of the chemistry of life, and ionizing radiation chemistry serves as an indispensable research tool for elucidation of the mechanism(s) underlying their reactions. The ever-increasing understanding of their involvement in diverse physiological and pathological processes has expanded the search for compounds that can diminish radical-induced damage. This review surveys the areas of research focusing on radical reactions and particularly with stable cyclic nitroxide radicals, which demonstrate unique antioxidative activities. Unlike common antioxidants that are progressively depleted under oxidative stress and yield secondary radicals, nitroxides are efficient radical scavengers yielding in most cases their respective oxoammonium cations, which are readily reduced back in the tissue to the nitroxide thus continuously being recycled. Nitroxides, which not only protect enzymes, cells, and laboratory animals from diverse kinds of biological injury, but also modify the catalytic activity of heme enzymes, could be utilized in chemical and biological systems serving as a research tool for elucidating mechanisms underlying complex chemical and biochemical processes.

Ecological Monitoring and Compliance Program Fiscal/Calendar Year 2004 Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtel Nevada

2005-03-01

The Ecological Monitoring and Compliance program, funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, monitors the ecosystem of the Nevada Test Site and ensures compliance with laws and regulations pertaining to Nevada Test Site biota. This report summarizes the program's activities conducted by Bechtel Nevada during the Fiscal Year 2004 and the additional months of October, November, and December 2004, reflecting a change in the monitoring period to a calendar year rather than a fiscal year as reported in the past. This change in the monitoring period was made to better accommodate information requiredmore » for the Nevada Test Site Environmental Report, which reports on a calendar year rather than a fiscal year. Program activities included: (1) biological surveys at proposed construction sites, (2) desert tortoise compliance, (3) ecosystem mapping and data management, (4) sensitive species and unique habitat monitoring, (5) habitat restoration monitoring, and (6) biological monitoring at the Hazardous Materials Spill Center.« less

AMPK/FIS1-Mediated Mitophagy Is Required for Self-Renewal of Human AML Stem Cells.

PubMed

Pei, Shanshan; Minhajuddin, Mohammad; Adane, Biniam; Khan, Nabilah; Stevens, Brett M; Mack, Stephen C; Lai, Sisi; Rich, Jeremy N; Inguva, Anagha; Shannon, Kevin M; Kim, Hyunmin; Tan, Aik-Choon; Myers, Jason R; Ashton, John M; Neff, Tobias; Pollyea, Daniel A; Smith, Clayton A; Jordan, Craig T

2018-06-06

Leukemia stem cells (LSCs) are thought to drive the genesis of acute myeloid leukemia (AML) as well as relapse following chemotherapy. Because of their unique biology, developing effective methods to eradicate LSCs has been a significant challenge. In the present study, we demonstrate that intrinsic overexpression of the mitochondrial dynamics regulator FIS1 mediates mitophagy activity that is essential for primitive AML cells. Depletion of FIS1 attenuates mitophagy and leads to inactivation of GSK3, myeloid differentiation, cell cycle arrest, and a profound loss of LSC self-renewal potential. Further, we report that the central metabolic stress regulator AMPK is also intrinsically activated in LSC populations and is upstream of FIS1. Inhibition of AMPK signaling recapitulates the biological effect of FIS1 loss. These data suggest a model in which LSCs co-opt AMPK/FIS1-mediated mitophagy as a means to maintain stem cell properties that may be otherwise compromised by the stresses induced by oncogenic transformation. Copyright © 2018 Elsevier Inc. All rights reserved.

The Role of Synthetic Biology in NASA's Missions

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

The time has come to for NASA to exploit synthetic biology in pursuit of its missions, including aeronautics, earth science, astrobiology and most notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particular space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement.

Beyond the vent: New perspectives on hydrothermal plumes and pelagic biology

NASA Astrophysics Data System (ADS)

Phillips, Brennan T.

2017-03-01

Submarine hydrothermal vent fields introduce buoyant plumes of chemically altered seawater to the deep-sea water column. Chemoautotrophic microbes exploit this energy source, facilitating seafloor-based primary production that evidence suggests may transfer to pelagic consumers. While most hydrothermal plumes have relatively small volumes, there are recent examples of large-scale plume events associated with periods of eruptive activity, which have had a pronounced effect on water-column biology. This correlation suggests that hydrothermal plumes may have influenced basin-scale ocean chemistry during periods of increased submarine volcanism during the Phanerozoic eon. This paper synthesizes a growing body of scientific evidence supporting the hypothesis that hydrothermal plumes are the energetic basis of unique deep-sea pelagic food webs. While many important questions remain concerning the biology of hydrothermal plumes, this discussion is not present in ongoing management efforts related to seafloor massive sulfide (SMS) mining. Increased research efforts, focused on high-resolution surveys of midwater biology relative to plume structures, are recommended to establish baseline conditions and monitor the impact of future mining-based disturbances to the pelagic biosphere.

Induction of interleukin 1 by synthetic and naturally occurring muramyl peptides.

PubMed

Dinarello, C A; Krueger, J M

1986-10-01

Like bacterial lipopolysaccharides (endotoxins), synthetic muramyl peptides (MPs) are thought to exert many of their biological effects by inducing the production of various mediators from host cells. Both synthetic muramyl dipeptide (MDP) and naturally occurring sleep factor (SF), which contains an MP structure, stimulate human monocytes to produce interleukin 1 (IL 1). IL 1 is a family of unique polypeptides that mediate a variety of host defense functions and possess several biological properties, many of which are shared with MPs. Endotoxins are potent inducers of IL 1, but polymyxin B, which blocks endotoxin's biological activities, has no effect on MP-induced IL 1 production. SF purified from human urine and SF isolated from the peritoneal fluid of patients undergoing chronic ambulatory peritoneal dialysis (CAPD) induce IL 1 when incubated with human mononuclear cells in vitro. SF from urine or CAPD fluid induces IL 1 production in the picrogram per milliliter range whereas synthetic MDP requires microgram per milliliter concentrations. Thus, both synthetic and naturally occurring MPs exert their biological effects, in part, by inducing IL 1.

Polyunsaturated fatty acid amides from the Zanthoxylum genus - from culinary curiosities to probes for chemical biology.

PubMed

Chruma, Jason J; Cullen, Douglas J; Bowman, Lydia; Toy, Patrick H

2018-01-25

Covering up to February 2017The pericarps of several species from the Zanthoxylum genus, a.k.a. the "prickly ash", have long been used for culinary purposes throughout Asia, most notably in the Sichuan (previously Szechuan) cuisine of Southwestern China, due to the unique tingling and numbing orosensations arising from a collection of polyunsaturated fatty acid amide (alkamide) constituents. The past decade has experienced dramatically increased academic and industrial interest in these pungent Zanthoxylum-derived alkamides, with a concomitant explosion in studies aimed at elucidating the specific biochemical mechanisms behind several medically-relevant biological activities exhibited by the natural products. This rapid increase in interest is partially fueled by advances in organic synthesis reported within the past few years that finally have allowed for the production of diastereomerically-pure Zanthoxylum alkamides and related analogs in multigram quantities. Herein is a comprehensive review of the discovery, total synthesis, and biological evaluation of Zanthoxylum-derived polyunsaturated fatty acid amides and synthetic analogues. Critical insights into how chemical synthesis can further benefit future chemical biology efforts in the field are also provided.

Recent Advances in the Discovery and Development of Marine Microbial Natural Products

PubMed Central

Xiong, Zhi-Qiang; Wang, Jian-Feng; Hao, Yu-You; Wang, Yong

2013-01-01

Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed. PMID:23528949

Recent advances in the discovery and development of marine microbial natural products.

PubMed

Xiong, Zhi-Qiang; Wang, Jian-Feng; Hao, Yu-You; Wang, Yong

2013-03-08

Marine microbial natural products (MMNPs) have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists during the last few decades. Numerous studies have indicated that diverse marine microbes appear to have the capacity to produce an impressive array of MMNPs exhibiting a wide variety of biological activities such as antimicrobial, anti-tumor, anti-inflammatory and anti-cardiovascular agents. Marine microorganisms represent an underexplored reservoir for the discovery of MMNPs with unique scaffolds and for exploitation in the pharmaceutical and agricultural industries. This review focuses on MMNPs discovery and development over the past decades, including innovative isolation and culture methods, strategies for discovering novel MMNPs via routine screenings, metagenomics, genomics, combinatorial biosynthesis, and synthetic biology. The potential problems and future directions for exploring MMNPs are also discussed.

Collaborative Systems Biology Projects for the Military Medical Community.

PubMed

Zalatoris, Jeffrey J; Scheerer, Julia B; Lebeda, Frank J

2017-09-01

This pilot study was conducted to examine, for the first time, the ongoing systems biology research and development projects within the laboratories and centers of the U.S. Army Medical Research and Materiel Command (USAMRMC). The analysis has provided an understanding of the breadth of systems biology activities, resources, and collaborations across all USAMRMC subordinate laboratories. The Systems Biology Collaboration Center at USAMRMC issued a survey regarding systems biology research projects to the eight U.S.-based USAMRMC laboratories and centers in August 2016. This survey included a data call worksheet to gather self-identified project and programmatic information. The general topics focused on the investigators and their projects, on the project's research areas, on omics and other large data types being collected and stored, on the analytical or computational tools being used, and on identifying intramural (i.e., USAMRMC) and extramural collaborations. Among seven of the eight laboratories, 62 unique systems biology studies were funded and active during the final quarter of fiscal year 2016. Of 29 preselected medical Research Task Areas, 20 were associated with these studies, some of which were applicable to two or more Research Task Areas. Overall, studies were categorized among six general types of objectives: biological mechanisms of disease, risk of/susceptibility to injury or disease, innate mechanisms of healing, diagnostic and prognostic biomarkers, and host/patient responses to vaccines, and therapeutic strategies including host responses to therapies. We identified eight types of omics studies and four types of study subjects. Studies were categorized on a scale of increasing complexity from single study subject/single omics technology studies (23/62) to studies integrating results across two study subject types and two or more omics technologies (13/62). Investigators at seven USAMRMC laboratories had collaborations with systems biology experts from 18 extramural organizations and three other USAMRMC laboratories. Collaborators from six USAMRMC laboratories and 58 extramural organizations were identified who provided additional research expertise to these systems biology studies. At the end of fiscal year 2016, USAMRMC laboratories self-reported 66 systems biology/computational biology studies (62 of which were unique) with 25 intramural and 81 extramural collaborators. Nearly two-thirds were led by or in collaboration with the U.S. Army Telemedicine and Advanced Technology Research Center/Department of Defense Biotechnology High-Performance Computing Software Applications Institute and U.S. Army Center for Environmental Health Research. The most common study objective addressed biological mechanisms of disease. The most common types of Research Task Areas addressed infectious diseases (viral and bacterial) and chemical agents (environmental toxicant exposures, and traditional and emerging chemical threats). More than 40% of the studies (27/62) involved collaborations between the reporting USAMRMC laboratory and one other organization. Nearly half of the studies (30/62) involved collaborations between the reporting USAMRMC laboratory and at least two other organizations. These survey results indicate that USAMRMC laboratories are compliant with data-centric policy and guidance documents whose goals are to prevent redundancy and promote collaborations by sharing data and leveraging capabilities. These results also serve as a foundation to make recommendations for future systems biology research efforts. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.

PubMed

Aggarwal, Bharat B; Yuan, Wei; Li, Shiyou; Gupta, Subash C

2013-09-01

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Redox-signals and macrophage biology (for the upcoming issue of molecular aspects of medicine on signaling by reactive oxygen species).

PubMed

Weigert, Andreas; von Knethen, Andreas; Fuhrmann, Dominik; Dehne, Nathalie; Brüne, Bernhard

2018-01-11

Macrophages are known for their versatile role in biology. They sense and clear structures that contain exogenous or endogenous pathogen-associated molecular patterns. This process is tightly linked to the production of a mixture of potentially harmful oxidants and cytokines. Their inherent destructive behavior is directed against foreign material or structures of 'altered self', which explains the role of macrophages during innate immune reactions and inflammation. However, there is also another side of macrophages when they turn into a tissue regenerative, pro-resolving, and healing phenotype. Phenotype changes of macrophages are termed macrophage polarization, representing a continuum between classical and alternative activation. Macrophages as the dominating producers of superoxide/hydrogen peroxide and nitric oxide are not only prone to oxidative modifications but also to more subtle signaling properties of redox-active molecules conveying redox regulation. We review basic concepts of the enzymatic nitric oxide and superoxide production within macrophages, refer to their unique chemical reactions and outline biological consequences not only for macrophage biology but also for their communication with cells in the microenvironment. These considerations link hypoxia to the NO system, addressing feedforward as well as feedback circuits. Moreover, we summarize the role of redox-signaling affecting epigenetics and reflect the central role of mitochondrial-derived oxygen species in inflammation. To better understand the diverse functions of macrophages during initiation as well as resolution of inflammation and to decode their versatile roles during innate and adaptive immunity with the entire spectrum of cell protective towards cell destructive activities we need to appreciate the signaling properties of redox-active species. Herein we discuss macrophage responses in terms of nitric oxide and superoxide formation with the modulating impact of hypoxia. Copyright © 2018. Published by Elsevier Ltd.

Synthetic Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2015-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Future of Chemical Engineering: Integrating Biology into the Undergraduate ChE Curriculum

ERIC Educational Resources Information Center

Mosto, Patricia; Savelski, Mariano; Farrell, Stephanie H.; Hecht, Gregory B.

2007-01-01

Integrating biology in the chemical engineering curriculum seems to be the future for chemical engineering programs nation and worldwide. Rowan University's efforts to address this need include a unique chemical engineering curriculum with an intensive biology component integrated throughout from freshman to senior years. Freshman and Sophomore…

Using Information and Communication Technology (ICT) to the Maximum: Learning and Teaching Biology with Limited Digital Technologies

ERIC Educational Resources Information Center

Van Rooy, Wilhelmina S.

2012-01-01

Background: The ubiquity, availability and exponential growth of digital information and communication technology (ICT) creates unique opportunities for learning and teaching in the senior secondary school biology curriculum. Digital technologies make it possible for emerging disciplinary knowledge and understanding of biological processes…

On the Development, Characterization, and Use of Protein Fluorescence and Infrared Spectroscopic Probes

NASA Astrophysics Data System (ADS)

Hilaire, Mary Rose

Proteins possess unique physical and chemical properties that allow them to carry out a wide variety of biological activities and functions. While it is generally understood that a protein's function is dictated by its structure and dynamics, arriving at a molecule-level understanding of the underlying structure-dynamics-function relationship still poses a challenging task in many cases. This is due, at least in part, to the fact that we lack the ability to take snapshots along the reaction coordinate of proteins with sufficient temporal and structural resolution. Therefore, to improve one's ability to acquire site-specific structural and/or environmental information of proteins via either infrared (IR) or fluorescence spectroscopy, the main focus of this thesis is to develop and characterize amino acid-based spectroscopic probes as well as to use such probes to study important biological questions. Specifically, we show that (1) p-cyanophenylalanine and selenomethionine constitute an efficient fluorophore-quencher pair, useful for characterizing protein conformational changes that occur on a short distance; (2) 4-cyanotryptophan is a novel blue fluorescent amino acid, applicable for biological imaging due to its unique photophysical properties; (3) the dielectric constant inside the hydrophobic interior of staphylococcal nuclease is about 10-15, significantly larger than previously assumed; and (4) a single mutation in a short segment of the protein transthyretin (i.e., 110-115) induces formation of amyloid fibrils consisting of both beta- and alpha-sheets, where the latter is a proposed structure in proteins, but has never been observed previously.

A Putative Gene Cluster from a Lyngbya wollei Bloom that Encodes Paralytic Shellfish Toxin Biosynthesis

PubMed Central

Mihali, Troco K.; Carmichael, Wayne W.; Neilan, Brett A.

2011-01-01

Saxitoxin and its analogs cause the paralytic shellfish-poisoning syndrome, adversely affecting human health and coastal shellfish industries worldwide. Here we report the isolation, sequencing, annotation, and predicted pathway of the saxitoxin biosynthetic gene cluster in the cyanobacterium Lyngbya wollei. The gene cluster spans 36 kb and encodes enzymes for the biosynthesis and export of the toxins. The Lyngbya wollei saxitoxin gene cluster differs from previously identified saxitoxin clusters as it contains genes that are unique to this cluster, whereby the carbamoyltransferase is truncated and replaced by an acyltransferase, explaining the unique toxin profile presented by Lyngbya wollei. These findings will enable the creation of toxin probes, for water monitoring purposes, as well as proof-of-concept for the combinatorial biosynthesis of these natural occurring alkaloids for the production of novel, biologically active compounds. PMID:21347365

Specific detection of the cleavage activity of mycobacterial enzymes using a quantum dot based DNA nanosensor

NASA Astrophysics Data System (ADS)

Jepsen, Morten Leth; Harmsen, Charlotte; Godbole, Adwait Anand; Nagaraja, Valakunja; Knudsen, Birgitta R.; Ho, Yi-Ping

2015-12-01

We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes.We present a quantum dot based DNA nanosensor specifically targeting the cleavage step in the reaction cycle of the essential DNA-modifying enzyme, mycobacterial topoisomerase I. The design takes advantages of the unique photophysical properties of quantum dots to generate visible fluorescence recovery upon specific cleavage by mycobacterial topoisomerase I. This report, for the first time, demonstrates the possibility to quantify the cleavage activity of the mycobacterial enzyme without the pre-processing sample purification or post-processing signal amplification. The cleavage induced signal response has also proven reliable in biological matrices, such as whole cell extracts prepared from Escherichia coli and human Caco-2 cells. It is expected that the assay may contribute to the clinical diagnostics of bacterial diseases, as well as the evaluation of treatment outcomes. Electronic supplementary information (ESI) available: Characterization of the QD-based DNA Nanosensor. See DOI: 10.1039/c5nr06326d

Systems interface biology

PubMed Central

Doyle, Francis J; Stelling, Jörg

2006-01-01

The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Hence, the interface between systems and biology is of mutual benefit to both disciplines. PMID:16971329

Zinc complexes developed as metallopharmaceutics for treating diabetes mellitus based on the bio-medicinal inorganic chemistry.

PubMed

Yoshikawa, Yutaka; Yasui, Hiroyuki

2012-01-01

Biological trace metals such as iron, zinc, copper, and manganese are essential to life and health of humans, and the success of platinum drugs in the cancer chemotherapy has rapidly grown interest in developing inorganic pharmaceutical agents in medicinal chemistry, that is, medicinal inorganic chemistry, using essential elements and other biological trace metals. Transition metal complexes with unique chemical structures may be useful alternatives to the drugs available to address some of the incurable diseases. In this review, we emphasize that metal complexes are an expanding of interest in the research field of treatment of diabetes mellitus. Especially, orally active anti-diabetic and anti-metabolic syndrome zinc complexes have been developed and progressed since the discovery in 2001, where several highly potent anti-diabetic zinc complexes with different coordination structures have quite recently been disclosed, using experimental diabetic animals. In all of the complexes discussed, zinc is found to be biologically active and function by interacting with some target proteins related with diabetes mellitus. The design and screening of zinc complexes with higher activity is not efficient without consideration of the translational research. For the development of a clinically useful metallopharmaceutics, the research of zinc complexes on the long-term toxicity including side effects, clear-cut evidence of target molecule for the in vivo pharmacological action, and good pharmacokinetic property are essential in the current and future studies.

Hibiscus latent Fort Pierce virus in Brazil and synthesis of its biologically active full-length cDNA clone.

PubMed

Gao, Ruimin; Niu, Shengniao; Dai, Weifang; Kitajima, Elliot; Wong, Sek-Man

2016-10-01

A Brazilian isolate of Hibiscus latent Fort Pierce virus (HLFPV-BR) was firstly found in a hibiscus plant in Limeira, SP, Brazil. RACE PCR was carried out to obtain the full-length sequences of HLFPV-BR which is 6453 nucleotides and has more than 99.15 % of complete genomic RNA nucleotide sequence identity with that of HLFPV Japanese isolate. The genomic structure of HLFPV-BR is similar to other tobamoviruses. It includes a 5' untranslated region (UTR), followed by open reading frames encoding for a 128-kDa protein and a 188-kDa readthrough protein, a 38-kDa movement protein, 18-kDa coat protein, and a 3' UTR. Interestingly, the unique feature of poly(A) tract is also found within its 3'-UTR. Furthermore, from the total RNA extracted from the local lesions of HLFPV-BR-infected Chenopodium quinoa leaves, a biologically active, full-length cDNA clone encompassing the genome of HLFPV-BR was amplified and placed adjacent to a T7 RNA polymerase promoter. The capped in vitro transcripts from the cloned cDNA were infectious when mechanically inoculated into C. quinoa and Nicotiana benthamiana plants. This is the first report of the presence of an isolate of HLFPV in Brazil and the successful synthesis of a biologically active HLFPV-BR full-length cDNA clone.

Usnic acid.

PubMed

Ingólfsdóttir, K

2002-12-01

Since its first isolation in 1844, usnic acid [2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione] has become the most extensively studied lichen metabolite and one of the few that is commercially available. Usnic acid is uniquely found in lichens, and is especially abundant in genera such as Alectoria, Cladonia, Usnea, Lecanora, Ramalina and Evernia. Many lichens and extracts containing usnic acid have been utilized for medicinal, perfumery, cosmetic as well as ecological applications. Usnic acid as a pure substance has been formulated in creams, toothpaste, mouthwash, deodorants and sunscreen products, in some cases as an active principle, in others as a preservative. In addition to antimicrobial activity against human and plant pathogens, usnic acid has been shown to exhibit antiviral, antiprotozoal, antiproliferative, anti-inflammatory and analgesic activity. Ecological effects, such as antigrowth, antiherbivore and anti-insect properties, have also been demonstrated. A difference in biological activity has in some cases been observed between the two enantiomeric forms of usnic acid. Recently health food supplements containing usnic acid have been promoted for use in weight reduction, with little scientific support. The emphasis of the current review is on the chemistry and biological activity of usnic acid and its derivatives in addition to rational and ecologically acceptable methods for provision of this natural compound on a large scale.

Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants

PubMed Central

Regan, Kelly; Wang, Kanix; Doughty, Emily; Li, Haiquan; Li, Jianrong; Lee, Younghee; Kann, Maricel G

2012-01-01

Objective Although trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. Materials and methods An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism. Results Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). Discussion The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein–protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP). Conclusion These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as ‘unique personal variants’. They also provide insight for identifying novel targets, for repositioning drugs, and for personal therapeutics. PMID:22319180

Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel-enzyme hybrids.

PubMed

Ikeda, Masato; Tanida, Tatsuya; Yoshii, Tatsuyuki; Kurotani, Kazuya; Onogi, Shoji; Urayama, Kenji; Hamachi, Itaru

2014-06-01

Soft materials that exhibit stimuli-responsive behaviour under aqueous conditions (such as supramolecular hydrogels composed of self-assembled nanofibres) have many potential biological applications. However, designing a macroscopic response to structurally complex biochemical stimuli in these materials still remains a challenge. Here we show that redox-responsive peptide-based hydrogels have the ability to encapsulate enzymes and still retain their activities. Moreover, cooperative coupling of enzymatic reactions with the gel response enables us to construct unique stimuli-responsive soft materials capable of sensing a variety of disease-related biomarkers. The programmable gel-sol response (even to biological samples) is visible to the naked eye. Furthermore, we built Boolean logic gates (OR and AND) into the hydrogel-enzyme hybrid materials, which were able to sense simultaneously plural specific biochemicals and execute a controlled drug release in accordance with the logic operation. The intelligent soft materials that we have developed may prove valuable in future medical diagnostics or treatments.

Preparation and development of block copolypeptide vesicles and hydrogels for biological and medical applications.

PubMed

Deming, Timothy J

2014-01-01

There have been many recent advances in the controlled polymerization of α-amino acid-N-carboxyanhydride (NCA) monomers into well-defined block copolypeptides. Transition metal initiating systems allow block copolypeptide synthesis with excellent control over number and lengths of block segments, chain length distribution, and chain-end functionality. Using this and other methods, block copolypeptides of controlled dimensions have been prepared and their self-assembly into organized structures studied by many research groups. The ability of well-defined block copolypeptides to assemble into supramolecular copolypeptide vesicles and hydrogels has led to the development of these materials for use in biological and medical applications. These assemblies have been found to possess unique properties that are derived from the amino acid building blocks and ordered conformations of the polypeptide segments. Recent work on the incorporation of active and stimulus-responsive functionality in these materials has tremendously increased their potential for use in biological and medical studies. © 2014 Wiley Periodicals, Inc.

Chemistry and biology of natural and designed enediynes.

PubMed Central

Nicolaou, K C; Smith, A L; Yue, E W

1993-01-01

Ever since the initial reports of the enediyne anticancer antibiotics in the late 1980s, researchers from a number of disciplines have been devoting increasing attention to their chemistry, biology, and potential medical applications. Synthetic chemists and molecular designers have been engaged in attempts to synthesize these molecules and to model their unique architecture. Considerable efforts have been directed at understanding and mimicking the various processes involved in the targeting, activation, and DNA cleavage associated with these natural products. This review summarizes the main contributions to the field, with particular emphasis on work from our laboratories. Highlights include studies of the Bergman reaction, which is central to the mechanism of action of enediynes, the design and chemical synthesis of a number of these systems, and biological studies with selected molecules. Finally, the total synthesis of calicheamicin gamma 1I, the most prominent member of this class of naturally occurring compounds, is discussed. Images Fig. 2 Fig. 5 Fig. 6 PMID:8327459

Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel-enzyme hybrids

NASA Astrophysics Data System (ADS)

Ikeda, Masato; Tanida, Tatsuya; Yoshii, Tatsuyuki; Kurotani, Kazuya; Onogi, Shoji; Urayama, Kenji; Hamachi, Itaru

2014-06-01

Soft materials that exhibit stimuli-responsive behaviour under aqueous conditions (such as supramolecular hydrogels composed of self-assembled nanofibres) have many potential biological applications. However, designing a macroscopic response to structurally complex biochemical stimuli in these materials still remains a challenge. Here we show that redox-responsive peptide-based hydrogels have the ability to encapsulate enzymes and still retain their activities. Moreover, cooperative coupling of enzymatic reactions with the gel response enables us to construct unique stimuli-responsive soft materials capable of sensing a variety of disease-related biomarkers. The programmable gel-sol response (even to biological samples) is visible to the naked eye. Furthermore, we built Boolean logic gates (OR and AND) into the hydrogel-enzyme hybrid materials, which were able to sense simultaneously plural specific biochemicals and execute a controlled drug release in accordance with the logic operation. The intelligent soft materials that we have developed may prove valuable in future medical diagnostics or treatments.

A Novel Characterization of Amalgamated Networks in Natural Systems

PubMed Central

Barranca, Victor J.; Zhou, Douglas; Cai, David

2015-01-01

Densely-connected networks are prominent among natural systems, exhibiting structural characteristics often optimized for biological function. To reveal such features in highly-connected networks, we introduce a new network characterization determined by a decomposition of network-connectivity into low-rank and sparse components. Based on these components, we discover a new class of networks we define as amalgamated networks, which exhibit large functional groups and dense connectivity. Analyzing recent experimental findings on cerebral cortex, food-web, and gene regulatory networks, we establish the unique importance of amalgamated networks in fostering biologically advantageous properties, including rapid communication among nodes, structural stability under attacks, and separation of network activity into distinct functional modules. We further observe that our network characterization is scalable with network size and connectivity, thereby identifying robust features significant to diverse physical systems, which are typically undetectable by conventional characterizations of connectivity. We expect that studying the amalgamation properties of biological networks may offer new insights into understanding their structure-function relationships. PMID:26035066

Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein

PubMed Central

Naciff, Jorge M.; Khambatta, Zubin S.; Carr, Gregory J.; Tiesman, Jay P.; Singleton, David W.; Khan, Sohaib A.; Daston, George P.

2016-01-01

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES’ estrogenic activity was identified by comparing the Ishikawa cells’ response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro. Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. PMID:26865667

Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein.

PubMed

Naciff, Jorge M; Khambatta, Zubin S; Carr, Gregory J; Tiesman, Jay P; Singleton, David W; Khan, Sohaib A; Daston, George P

2016-05-01

To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 μM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time-dependent manner (P ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 μM). The GES' estrogenic activity was identified by comparing the Ishikawa cells' response to GES versus 17 α-ethynyl estradiol (EE, at equipotent doses, ie, 10 μM vs 1 μM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Marine products with anti-protozoal activity: a review.

PubMed

García, Marley; Monzote, Lianet

2014-01-01

The marine organisms are a rich source of varied natural products with unique functionality. A variety of natural products of new molecular structures with diverse biological activities have been reported from marine flora and fauna for treatment and/or prevention of human diseases. The present review briefly illustrates current status of marine products as antiprotozoal agents. The in vitro and in vivo studies of marine algae, invertebrates and micro-organism against different protozoa parasites are included. The marine products studied, according to international criterions for selection of more promisory products in the different models reported, demonstrated their potentialities as antiprozoal agents. Herein, the interest of scientific community to search new alternatives from marine environment has been demonstrated.

Recent Advances in Skin-Inspired Sensors Enabled by Nanotechnology

NASA Astrophysics Data System (ADS)

Loh, Kenneth J.; Azhari, Faezeh

2012-07-01

The highly optimized performance of nature's creations and biological assemblies has inspired the development of their bio-inspired artificial counterparts that can potentially outperform conventional systems. In particular, the skin of humans, animals, and insects exhibits unique functionalities and properties and has subsequently led to active research in developing skin-inspired sensors. This paper presents a summary of selected work related to skin-inspired tactile, distributed strain, and artificial hair cell flow sensors, with a particular focus on technologies enabled by recent advancements in the nanotechnology domain. The purpose is not to present a comprehensive review on this broad subject matter but rather to use selected work to outline the diversity of current research activities.

Reversible Redox Activity by Ion-pH Dually Modulated Duplex Formation of i-Motif DNA with Complementary G-DNA.

PubMed

Chang, Soyoung; Kilic, Tugba; Lee, Chang Kee; Avci, Huseyin; Bae, Hojae; Oskui, Shirin Mesbah; Jung, Sung Mi; Shin, Su Ryon; Kim, Seon Jeong

2018-04-08

The unique biological features of supramolecular DNA have led to an increasing interest in biomedical applications such as biosensors. We have developed an i-motif and G-rich DNA conjugated single-walled carbon nanotube hybrid materials, which shows reversible conformational switching upon external stimuli such as pH (5 and 8) and presence of ions (Li⁺ and K⁺). We observed reversible electrochemical redox activity upon external stimuli in a quick and robust manner. Given the ease and the robustness of this method, we believe that pH- and ion-driven reversible DNA structure transformations will be utilized for future applications for developing novel biosensors.

Where Synthetic Biology Meets ET

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Raman Spectral Signatures as Conformational Probes of Biomolecules

NASA Astrophysics Data System (ADS)

Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana

2009-06-01

A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.

Raman Spectral Signatures as Conformational Probes of Biomolecules

NASA Astrophysics Data System (ADS)

Bar, Ilana; Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman

2009-03-01

A first application of ionization-loss stimulated Raman spectroscopy (ILSRS) monitoring the spectral features of four conformers of a gas phase neurotransmitter (2-phenylethylamine) is reported. The Raman spectra of the conformers show bands that uniquely identify the conformational structure of the molecule and are well matched by density functional theory calculations. The measurement of spectral signatures by ILSRS in an extended spectral range, with a relatively convenient laser source, is extremely important, allowing enhanced accessibility to intra- and inter-molecular forces, which are significant in biological structure and activity.

Raman spectral signatures as conformational probes of gas phase flexible molecules

NASA Astrophysics Data System (ADS)

Golan, Amir; Mayorkas, Nitzan; Rosenwaks, Salman; Bar, Ilana

2009-07-01

A novel application of ionization-loss stimulated Raman spectroscopy (ILSRS) for monitoring the spectral features of four conformers of a gas phase flexible molecule is reported. The Raman spectral signatures of four conformers of 2-phenylethylamine are well matched by the results of density functional theory calculations, showing bands uniquely identifying the structures. The measurement of spectral signatures by ILSRS in an extended spectral range, with a conventional laser source, is instrumental in facilitating the unraveling of intra- and intermolecular interactions that are significant in biological structure and activity.

Soft Biological and Composite Nanomaterials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Firestone, Millicent

2016-04-01

The goal of the Center for Integrated Nanotechnologies (CINT) is to plays a leadership role in integration of nanostructured materials to enable novel capabilities and applications through its function as a Department of Energy/Office of Science Nanoscale Science Research Center (NSRC) national user facility. By coupling open access to unique and world-class capabilities and scientific expertise to an active user community, CINT supports high-impact research that no other single institution could achieve – the whole of CINT including its user community is greater than the sum of its parts.

11-Step Total Synthesis of (−)-Maoecrystal V

PubMed Central

2016-01-01

An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (−)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product. PMID:27457680

Articular cartilage. Part I. The normal joint.

PubMed

Muehleman, C; Arsenis, C H

1995-05-01

Articular hyaline cartilage is of interest to both the clinician and the basic scientist because of its unique physical and chemical properties which are a consequence of its biochemical composition. Although it is a tissue which is hypocellular, avascular, and also lacks nerves and lymphatics, it is active in synthesis and degradation. Articular cartilage responds to the forces to which it is subjected and, in this way, maintains its integrity as long as those forces do not exceed the tissue's capacity for repair or permanently change the biologic response of the cells.

Nucleophilic ring opening reactions of aziridines.

PubMed

Akhtar, Rabia; Naqvi, Syed Ali Raza; Zahoor, Ameer Fawad; Saleem, Sameera

2018-05-04

Aziridine ring opening reactions have gained tremendous importance in the synthesis of nitrogen containing biologically active molecules. During recent years, a great effort has been put forward by scientists toward unique bond construction methodologies via ring opening of aziridines. In this regard, a wide range of chiral metal- and organo-catalyzed desymmetrization reactions of aziridines have been reported with carbon, sulfur, oxygen, nitrogen, halogen, and other nucleophiles. In this review, an outline of methodologies adopted by a number of scientists during 2013-2017 for aziridine ring opening reactions as well as their synthetic applications is described.

Conotoxin Φ-MiXXVIIA from the Superfamily G2 Employs a Novel Cysteine Framework that Mimics Granulin and Displays Anti-Apoptotic Activity.

PubMed

Jin, Ai-Hua; Dekan, Zoltan; Smout, Michael J; Wilson, David; Dutertre, Sébastien; Vetter, Irina; Lewis, Richard J; Loukas, Alex; Daly, Norelle L; Alewood, Paul F

2017-11-20

Conotoxins are a large family of disulfide-rich peptides that contain unique cysteine frameworks that target a broad range of ion channels and receptors. We recently discovered the 33-residue conotoxin Φ-MiXXVIIA from Conus miles with a novel cysteine framework comprising three consecutive cysteine residues and four disulfide bonds. Regioselective chemical synthesis helped decipher the disulfide bond connectivity and the structure of Φ-MiXXVIIA was determined by NMR spectroscopy. The 3D structure displays a unique topology containing two β-hairpins that resemble the N-terminal domain of granulin. Similar to granulin, Φ-MiXXVIIA promotes cell proliferation (EC 50 17.85 μm) while inhibiting apoptosis (EC 50 2.2 μm). Additional framework XXVII sequences were discovered with homologous signal peptides that define the new conotoxin superfamily G2. The novel structure and biological activity of Φ-MiXXVIIA expands the repertoire of disulfide-rich conotoxins that recognize mammalian receptors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Traditional Medicine and Modern Medicine from Natural Products.

PubMed

Yuan, Haidan; Ma, Qianqian; Ye, Li; Piao, Guangchun

2016-04-29

Natural products and traditional medicines are of great importance. Such forms of medicine as traditional Chinese medicine, Ayurveda, Kampo, traditional Korean medicine, and Unani have been practiced in some areas of the world and have blossomed into orderly-regulated systems of medicine. This study aims to review the literature on the relationship among natural products, traditional medicines, and modern medicine, and to explore the possible concepts and methodologies from natural products and traditional medicines to further develop drug discovery. The unique characteristics of theory, application, current role or status, and modern research of eight kinds of traditional medicine systems are summarized in this study. Although only a tiny fraction of the existing plant species have been scientifically researched for bioactivities since 1805, when the first pharmacologically-active compound morphine was isolated from opium, natural products and traditional medicines have already made fruitful contributions for modern medicine. When used to develop new drugs, natural products and traditional medicines have their incomparable advantages, such as abundant clinical experiences, and their unique diversity of chemical structures and biological activities.

Study on Transformation of Ginsenosides in Different Methods

PubMed Central

Zheng, Meng-meng; Xu, Fang-xue; Li, Yu-juan; Xi, Xiao-zhi; Cui, Xiao-wei

2017-01-01

Ginseng is a traditional Chinese medicine and has the extensive pharmacological activity. Ginsenosides are the major constituent in ginseng and have the unique biological activity and medicinal value. Ginsenosides have the good effects on antitumor, anti-inflammatory, antioxidative and inhibition of the cell apoptosis. Studies have showed that the major ginsenosides could be converted into rare ginsenosides, which played a significant role in exerting pharmacological activity. However, the contents of some rare ginsenosides are very little. So it is very important to find the effective way to translate the main ginsenosides to rare ginsenosides. In order to provide the theoretical foundation for the transformation of ginsenoside in vitro, in this paper, many methods of the transformation of ginsenoside were summarized, mainly including physical methods, chemical methods, and biotransformation methods. PMID:29387726

Defensive strategies in Geranium sylvaticum, Part 2: Roles of water-soluble tannins, flavonoids and phenolic acids against natural enemies.

PubMed

Tuominen, Anu

2013-11-01

Geranium sylvaticum is a common herbaceous plant in Fennoscandia, which has a unique phenolic composition. Ellagitannins, proanthocyanidins, galloylglucoses, gallotannins, galloyl quinic acids and flavonoids possess variable distribution in its different organs. These phenolic compounds are thought to have an important role in plant-herbivore interactions. The aim of this study was to quantify these different water-soluble phenolic compounds and measure the biological activity of the eight organs of G. sylvaticum. Compounds were characterized and quantified using HPLC-DAD/MS, in addition, total proanthocyanidins were determined by BuOH-HCl assay and total phenolics by the Folin-Ciocalteau method. Two in vitro biological activity measurements were used: the prooxidant activity was measured by the browning assay and antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Organ extracts were fractionated using column chromatography on Sephadex LH-20 and the activities of fractions was similarly measured to evaluate which polyphenol groups contributed the most to the biological activity of each organ. The data on the activity of fractions were examined by multivariate data analysis. The water-soluble extracts of leaves and pistils, which contained over 30% of the dry weight as ellagitannins, showed the highest pro-oxidant activity among the organ extracts. Fraction analysis revealed that flavonoids and galloyl quinic acids also exhibited high pro-oxidant activity. In contrast, the most antioxidant active organ extracts were those of the main roots and hairy roots that contained high amounts of proanthocyanidins in addition to ellagitannins. Analysis of the fractions showed that especially ellagitannins and galloyl quinic acids have high antioxidant activity. We conclude that G. sylvaticum allocates a significant amount of tannins in those plant parts that are important to the fitness of the plant and susceptible to natural enemies, i.e. pistil and leaf tannins protect against insect herbivores and root tannins against soil pathogens. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biology Division Habrobracon Experiment P-1079

NASA Technical Reports Server (NTRS)

1968-01-01

Dosimetric analyses accumulated during the five-year period of the biosatellite program are summarized. These data are from a unique source placed in a unique optical bench, the biosatellite. Thus the multitudinous array of dosimeters was mandatory to give confidence in the experiment.

Anticancer activity of flavonoids isolated from Achyrocline satureioides in gliomas cell lines.

PubMed

Souza, Priscila Oliveira de; Bianchi, Sara Elis; Figueiró, Fabrício; Heimfarth, Luana; Moresco, Karla Suzana; Gonçalves, Rosângela Mayer; Hoppe, Juliana Bender; Klein, Caroline Peres; Salbego, Christianne Gazzana; Gelain, Daniel Pens; Bassani, Valquíria Linck; Zanotto Filho, Alfeu; Moreira, José Claudio Fonseca

2018-05-04

Achyrocline satureioides, popularly known as "marcela", is a medicinal plant found in South America. This plant is rich in flavonoids, which have been reported to exert numerous biological activities. The aim of this study was to purify, identify and evaluate the mechanisms underlining anticancer activity of A. satureioides flavonoids in glioma cell lines (U87, U251 and C6) as well as their comparative toxicity in normal brain cells (primary astrocytes, neurons and organotypic hippocampal cultures). The main flavonoids present in A. satureioides are luteolin, quercetin, 3-O-methyl-quercetin and achyrobichalcone, the later a very unique metabolite present in this plant. Isolated flavonoids as well as A. satureioides extracts reduced proliferation and clonogenic survival, and induced apoptosis of glioma cell lines. In addition, A. satureioides flavonoids potentiated the cytotoxic effect and apoptosis induction by the glioma chemotherapeutic temozolomide (TMZ). Importantly, A. satureioides flavonoids were less cytotoxic to astrocytes, neuron:astrocytes co-cultures and hippocampal cultures if compared to gliomas. Investigation of 10 cancer-related pathways showed a reduced activation of MYC and the Map kinases ERK and JNK by A. satureioides flavonoid-enriched extract, an effect not observed when individual flavonoids were evaluated. Altogether, the herein presented results show that A. satureioides extract possesses a combination of flavonoids, some unique for this plant, which have synergistic anticancer activity and potential for further studies in vivo. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nitric oxide in the stress axis.

PubMed

López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

1998-10-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

Physical Heterogeneity and Aquatic Community Function in River Networks

EPA Science Inventory

The geomorphological character of a river network provides the template upon which evolution acts to create unique biological communities. Deciphering commonly observed patterns and processes within riverine landscapes resulting from the interplay between physical and biological...

High Density or Urban Sprawl: What Works Best in Biology?

PubMed

Oreopoulos, John; Gray-Owen, Scott D; Yip, Christopher M

2017-02-28

With new approaches in imaging-from new tools or reagents to processing algorithms-come unique opportunities and challenges to our understanding of biological processes, structures, and dynamics. Although innovations in super-resolution imaging are affording novel perspectives into how molecules structurally associate and localize in response to, or in order to initiate, specific signaling events in the cell, questions arise as to how to interpret these observations in the context of biological function. Just as each neighborhood in a city has its own unique vibe, culture, and indeed density, recent work has shown that membrane receptor behavior and action is governed by their localization and association state. There is tremendous potential in developing strategies for tracking how the populations of these molecular neighborhoods change dynamically.

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

PubMed

Roybal, Kole T; Lim, Wendell A

2017-04-26

The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

PubMed Central

Roybal, Kole T.; Lim, Wendell A.

2017-01-01

The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases. PMID:28446063

Conditional clustering of temporal expression profiles

PubMed Central

Wang, Ling; Montano, Monty; Rarick, Matt; Sebastiani, Paola

2008-01-01

Background Many microarray experiments produce temporal profiles in different biological conditions but common cluster techniques are not able to analyze the data conditional on the biological conditions. Results This article presents a novel technique to cluster data from time course microarray experiments performed across several experimental conditions. Our algorithm uses polynomial models to describe the gene expression patterns over time, a full Bayesian approach with proper conjugate priors to make the algorithm invariant to linear transformations, and an iterative procedure to identify genes that have a common temporal expression profile across two or more experimental conditions, and genes that have a unique temporal profile in a specific condition. Conclusion We use simulated data to evaluate the effectiveness of this new algorithm in finding the correct number of clusters and in identifying genes with common and unique profiles. We also use the algorithm to characterize the response of human T cells to stimulations of antigen-receptor signaling gene expression temporal profiles measured in six different biological conditions and we identify common and unique genes. These studies suggest that the methodology proposed here is useful in identifying and distinguishing uniquely stimulated genes from commonly stimulated genes in response to variable stimuli. Software for using this clustering method is available from the project home page. PMID:18334028

Privileged scaffolds or promiscuous binders: a glance of pyrrolo[2,1-f][1,2,4]triazines and related bridgehead nitrogen heterocycles in medicinal chemistry.

PubMed

Song, Yu'ning; Zhan, Peng; Zhang, Qingzhu; Liu, Xinyong

2013-01-01

Pyrrolo[2,1-f][1,2,4]triazine template, a unique bridgehead nitrogen heterocycle, certainly deserves the title of "privileged scaffold" in the drug discovery field because of the versatility and potential to yield derivatives with a wide range of biological activities, such as anti-anaplastic lymphoma kinase (ALK), Janus kinase 2 (JAK2), VEGFR-2, EGFR and/or HER2, Met kinase, p38α mitogen-activated protein (MAP) kinase and insulin-like growth factor receptor (IGF-1R) kinase activities, etc. These different biological properties of pyrrolo[2,1-f][1,2,4]triazine derivatives have motivated new studies in searching for novel derivatives with improved activity and also other applications in pharmaceutical field. However, no systematic review is available in the literature on the pyrrolo[2,1- f][1,2,4]triazine derivatives concerning the design of potent drug-like compounds. Owing to the importance of this heterocyclic system, the present paper is an attempt to the pharmacological activities, structural modifications and the structure-activity relationship (SAR) reported for bridgehead nitrogen heterocycles in the current literature, making an effort to highlight the importance and therapeutic potentials of the pyrrolo[2,1-f][1,2,4]triazine scaffold and its bridgehead nitrogen bioisosters as heterocyclic privileged medicinal scaffolds.

Skin melanocytes: biology and development

PubMed Central

Wachulska, Małgorzata; Stasiewicz, Aneta; Tymińska, Agata

2013-01-01

In the human skin, melanocytes are present in the epidermis and hair follicles. The basic features of these cells are the ability to melanin production and the origin from neural crest cells. This last element is important because there are other cells able to produce melanin but of different embryonic origin (pigmented epithelium of retina, some neurons, adipocytes). The life cycle of melanocyte consists of several steps including differentiation of melanocyte lineage/s from neural crest, migration and proliferation of melanoblasts, differentiation of melanoblasts into melanocytes, proliferation and maturation of melanocytes at the target places (activity of melanogenic enzymes, melanosome formation and transport to keratinocytes) and eventual cell death (hair melanocytes). Melanocytes of the epidermis and hair are cells sharing some common features but in general they form biologically different populations living in unique niches of the skin. PMID:24278043

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kufareva, Irina; Gustavsson, Martin; Zheng, Yi

Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novelmore » epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.« less

Emerging role of the Jun N-terminal kinase interactome in human health.

PubMed

Guo, Xiao-Xi; An, Su; Yang, Yang; Liu, Ying; Hao, Qian; Tang, Tao; Xu, Tian-Rui

2018-02-08

The c-Jun N-terminal kinases (JNKs) are located downstream of Ras-mitogen activated protein kinase signaling cascades. More than 20 years of study has shown that JNKs control cell fate and many cellular functions. JNKs and their interacting proteins form a complicated network with diverse biological functions and physiological effects. Members of the JNK interactome include Jun, amyloid precursor protein, and insulin receptor substrate. Recent studies have shown that the JNK interactome is involved in tumorigenesis, neuron development, and insulin resistance. In this review, we summarize the features of the JNK interactome and classify its members into three groups: upstream regulators, downstream effectors, and scaffold partners. We also highlight the unique cellular signaling mechanisms of JNKs and provide more insights into the roles of the JNK interactome in human diseases. © 2018 International Federation for Cell Biology.

Nanomaterials as analytical tools for genosensors.

PubMed

Abu-Salah, Khalid M; Alrokyan, Salman A; Khan, Muhammad Naziruddin; Ansari, Anees Ahmad

2010-01-01

Nanomaterials are being increasingly used for the development of electrochemical DNA biosensors, due to the unique electrocatalytic properties found in nanoscale materials. They offer excellent prospects for interfacing biological recognition events with electronic signal transduction and for designing a new generation of bioelectronic devices exhibiting novel functions. In particular, nanomaterials such as noble metal nanoparticles (Au, Pt), carbon nanotubes (CNTs), magnetic nanoparticles, quantum dots and metal oxide nanoparticles have been actively investigated for their applications in DNA biosensors, which have become a new interdisciplinary frontier between biological detection and material science. In this article, we address some of the main advances in this field over the past few years, discussing the issues and challenges with the aim of stimulating a broader interest in developing nanomaterial-based biosensors and improving their applications in disease diagnosis and food safety examination.

Cloning, expression, purification and crystallographic studies of galectin-11 from domestic sheep (Ovis aries).

PubMed

Sakthivel, Dhanasekaran; Littler, Dene; Shahine, Adam; Troy, Sally; Johnson, Matthew; Rossjohn, Jamie; Piedrafita, David; Beddoe, Travis

2015-08-01

Galectins are an evolutionarily conserved family of proteins that translate glycan recognition into cellular effects. Galectin-11 is a unique member of the galectin family that is only expressed in ruminants such as sheep, goat and cattle and that plays a critical role in several important biological processes, such as reproduction and parasite-mediated innate immune responses. Currently, these two areas are of major importance for the sustainability of ruminant livestock production. Despite the emerging biological significance of galectin-11, no structural information is available. It is expected that structural studies will unravel the functional mechanisms of galectin-11 activity. Here, the expression, purification and crystallization of the ruminant-specific galectin-11 from domestic sheep and the collection of X-ray data to 2.0 Å resolution are reported.

Functional impact of splice isoform diversity in individual cells

PubMed Central

Yap, Karen; Makeyev, Eugene V.

2016-01-01

Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a ‘splicing noise’, co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities. PMID:27528755

Functional impact of splice isoform diversity in individual cells.

PubMed

Yap, Karen; Makeyev, Eugene V

2016-08-15

Alternative pre-mRNA splicing provides an effective means for expanding coding capacity of eukaryotic genomes. Recent studies suggest that co-expression of different splice isoforms may increase diversity of RNAs and proteins at a single-cell level. A pertinent question in the field is whether such co-expression is biologically meaningful or, rather, represents insufficiently stringent splicing regulation. Here we argue that isoform co-expression may produce functional outcomes that are difficult and sometimes impossible to achieve using other regulation strategies. Far from being a 'splicing noise', co-expression is often established through co-ordinated activity of specific cis-elements and trans-acting factors. Further work in this area may uncover new biological functions of alternative splicing (AS) and generate important insights into mechanisms allowing different cell types to attain their unique molecular identities. © 2016 The Author(s).

Nanomaterials as Analytical Tools for Genosensors

PubMed Central

Abu-Salah, Khalid M.; Alrokyan, Salman A.; Khan, Muhammad Naziruddin; Ansari, Anees Ahmad

2010-01-01

Nanomaterials are being increasingly used for the development of electrochemical DNA biosensors, due to the unique electrocatalytic properties found in nanoscale materials. They offer excellent prospects for interfacing biological recognition events with electronic signal transduction and for designing a new generation of bioelectronic devices exhibiting novel functions. In particular, nanomaterials such as noble metal nanoparticles (Au, Pt), carbon nanotubes (CNTs), magnetic nanoparticles, quantum dots and metal oxide nanoparticles have been actively investigated for their applications in DNA biosensors, which have become a new interdisciplinary frontier between biological detection and material science. In this article, we address some of the main advances in this field over the past few years, discussing the issues and challenges with the aim of stimulating a broader interest in developing nanomaterial-based biosensors and improving their applications in disease diagnosis and food safety examination. PMID:22315580

Rational Design of Novel Allosteric Dihydrofolate Reductase Inhibitors Showing Antibacterial Effects on Drug-Resistant Escherichia coli Escape Variants.

PubMed

Srinivasan, Bharath; Rodrigues, João V; Tonddast-Navaei, Sam; Shakhnovich, Eugene; Skolnick, Jeffrey

2017-07-21

In drug discovery, systematic variations of substituents on a common scaffold and bioisosteric replacements are often used to generate diversity and obtain molecules with better biological effects. However, this could saturate the small-molecule diversity pool resulting in drug resistance. On the other hand, conventional drug discovery relies on targeting known pockets on protein surfaces leading to drug resistance by mutations of critical pocket residues. Here, we present a two-pronged strategy of designing novel drugs that target unique pockets on a protein's surface to overcome the above problems. Dihydrofolate reductase, DHFR, is a critical enzyme involved in thymidine and purine nucleotide biosynthesis. Several classes of compounds that are structural analogues of the substrate dihydrofolate have been explored for their antifolate activity. Here, we describe 10 novel small-molecule inhibitors of Escherichia coli DHFR, EcDHFR, belonging to the stilbenoid, deoxybenzoin, and chalcone family of compounds discovered by a combination of pocket-based virtual ligand screening and systematic scaffold hopping. These inhibitors show a unique uncompetitive or noncompetitive inhibition mechanism, distinct from those reported for all known inhibitors of DHFR, indicative of binding to a unique pocket distinct from either substrate or cofactor-binding pockets. Furthermore, we demonstrate that rescue mutants of EcDHFR, with reduced affinity to all known classes of DHFR inhibitors, are inhibited at the same concentration as the wild-type. These compounds also exhibit antibacterial activity against E. coli harboring the drug-resistant variant of DHFR. This discovery is the first report on a novel class of inhibitors targeting a unique pocket on EcDHFR.

Nucleolar Targeting by Platinum: p53-Independent Apoptosis Follows rRNA Inhibition, Cell-Cycle Arrest, and DNA Compaction

PubMed Central

2015-01-01

TriplatinNC is a highly positively charged, substitution-inert derivative of the phase II clinical anticancer drug, BBR3464. Such substitution-inert complexes form a distinct subset of polynuclear platinum complexes (PPCs) interacting with DNA and other biomolecules through noncovalent interactions. Rapid cellular entry is facilitated via interaction with cell surface glycosoaminoglycans and is a mechanism unique to PPCs. Nanoscale secondary ion mass spectrometry (nanoSIMS) showed rapid distribution within cytoplasmic and nucleolar compartments, but not the nucleus. In this article, the downstream effects of nucleolar localization are described. In human colon carcinoma cells, HCT116, the production rate of 47S rRNA precursor transcripts was dramatically reduced as an early event after drug treatment. Transcriptional inhibition of rRNA was followed by a robust G1 arrest, and activation of apoptotic proteins caspase-8, -9, and -3 and PARP-1 in a p53-independent manner. Using cell synchronization and flow cytometry, it was determined that cells treated while in G1 arrest immediately, but cells treated in S or G2 successfully complete mitosis. Twenty-four hours after treatment, the majority of cells finally arrest in G1, but nearly one-third contained highly compacted DNA; a distinct biological feature that cannot be associated with mitosis, senescence, or apoptosis. This unique effect mirrored the efficient condensation of tRNA and DNA in cell-free systems. The combination of DNA compaction and apoptosis by TriplatinNC treatment conferred striking activity in platinum-resistant and/or p53 mutant or null cell lines. Taken together, our results support that the biological activity of TriplatinNC reflects reduced metabolic deactivation (substitution-inert compound not reactive to sulfur nucleophiles), high cellular accumulation, and novel consequences of high-affinity noncovalent DNA binding, producing a new profile and a further shift in the structure–activity paradigms for antitumor complexes. PMID:25407898

Modeling of S-Nitrosothiol-Thiol Reactions of Biological Significance: HNO Production by S-Thiolation Requires a Proton Shuttle and Stabilization of Polar Intermediates.

PubMed

Ivanova, Lena V; Cibich, Daniel; Deye, Gregory; Talipov, Marat R; Timerghazin, Qadir K

2017-04-18

Nitroxyl (HNO), a reduced form of the important gasotransmitter nitric oxide, exhibits its own unique biological activity. A possible biological pathway of HNO formation is the S-thiolation reaction between thiols and S-nitrosothiols (RSNOs). Our density functional theory (DFT) calculations suggested that S-thiolation proceeds through a proton transfer from the thiol to the RSNO nitrogen atom, which increases electrophilicity of the RSNO sulfur, followed by nucleophilic attack by thiol, yielding a charge-separated zwitterionic intermediate structure RSS + (R)N(H)O - (Zi), which decomposes to yield HNO and disulfide RSSR. In the gas phase, the proton transfer and the S-S bond formation are asynchronous, resulting in a high activation barrier (>40 kcal mol -1 ), making the reaction infeasible. However, the barrier can decrease below the S-N bond dissociation energy in RSNOs (≈30 kcal mol -1 ) upon transition into an aqueous environment that stabilizes Zi and provides a proton shuttle to synchronize the proton transfer and the S-S bond formation. These mechanistic features suggest that S-thiolation can easily lend itself to enzymatic catalysis and thus can be a possible route of endogenous HNO production. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A 13-week research-based biochemistry laboratory curriculum.

PubMed

Lefurgy, Scott T; Mundorff, Emily C

2017-09-01

Here, we present a 13-week research-based biochemistry laboratory curriculum designed to provide the students with the experience of engaging in original research while introducing foundational biochemistry laboratory techniques. The laboratory experience has been developed around the directed evolution of an enzyme chosen by the instructor, with mutations designed by the students. Ideal enzymes for this curriculum are able to be structurally modeled, solubly expressed, and monitored for activity by UV/Vis spectroscopy, and an example curriculum for haloalkane dehalogenase is given. Unique to this curriculum is a successful implementation of saturation mutagenesis and high-throughput screening of enzyme function, along with bioinformatics analysis, homology modeling, structural analysis, protein expression and purification, polyacrylamide gel electrophoresis, UV/Vis spectroscopy, and enzyme kinetics. Each of these techniques is carried out using a novel student-designed mutant library or enzyme variant unique to the lab team and, importantly, not described previously in the literature. Use of a well-established set of protocols promotes student data quality. Publication may result from the original student-generated hypotheses and data, either from the class as a whole or individual students that continue their independent projects upon course completion. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):437-448, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

An emerging trend in functional foods for the prevention of cardiovascular disease and diabetes: Marine algal polyphenols.

PubMed

Murray, Margaret; Dordevic, Aimee L; Ryan, Lisa; Bonham, Maxine P

2018-05-24

Marine macroalgae are gaining recognition among the scientific community as a significant source of functional food ingredients. Due to the harsh environments in which macroalgae survive, they produce unique bioactive compounds that are not found in terrestrial plants. Polyphenols are the predominant bioactive compound in brown algae and are accountable for the majority of its biological activity. Phlorotannins are a type of polyphenol that are unique to marine sources and have exhibited protective effects against hyperglycemia, hyperlipidemia, inflammation and oxidative stress, known risk factors for cardiovascular disease and diabetic complications, in cell culture, animal studies and some human studies. This review updates the information on marine polyphenols, with a particular focus on phlorotannins and their potential health benefits in relation to the prevention and treatment of risk factors for type 2 diabetes and cardiovascular diseases.

Electrochemistry at Edge of Single Graphene Layer in a Nanopore

PubMed Central

Banerjee, Shouvik; Shim, Jiwook; Rivera, Jose; Jin, Xiaozhong; Estrada, David; Solovyeva, Vita; You, Xiuque; Pak, James; Pop, Eric; Aluru, Narayana; Bashir, Rashid

2013-01-01

We study the electrochemistry of single layer graphene edges using a nanopore-based structure consisting of stacked graphene and Al2O3 dielectric layers. Nanopores, with diameters ranging from 5 to 20 nm, are formed by an electron beam sculpting process on the stacked layers. This leads to unique edge structure which, along with the atomically thin nature of the embedded graphene electrode, demonstrates electrochemical current densities as high as 1.2 × 104 A/cm2. The graphene edge embedded structure offers a unique capability to study the electrochemical exchange at an individual graphene edge, isolated from the basal plane electrochemical activity. We also report ionic current modulation in the nanopore by biasing the embedded graphene terminal with respect to the electrodes in the fluid. The high electrochemical specific current density for a graphene nanopore-based device can have many applications in sensitive chemical and biological sensing, and energy storage devices. PMID:23249127

Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis.

PubMed

Cherney, Emily C; Baran, Phil S

2011-04-01

Terpenes and alkaloids are ever-growing classes of natural products that provide new molecular structures which inspire chemists and possess a broad range of biological activity. Terpenoid-alkaloids originate from the same prenyl units that construct terpene skeletons. However, during biosynthesis, a nitrogen atom (or atoms) is introduced in the form of β-aminoethanol, ethylamine, or methylamine. Nitrogen incorporation can occur either before, during, or after the cyclase phase. The outcome of this unique biosynthesis is the formation of natural products containing unprecedented structures. These complex structural motifs expose current limitations in organic chemistry, thus providing opportunities for invention. This review focuses on total syntheses of terpenoid-alkaloids and unique issues presented by this class of natural products. More specifically, it examines how these syntheses relate to the way terpenoid-alkaloids are made in Nature. Developments in chemistry that have facilitated these syntheses are emphasized, as well as chemical technology needed to conquer those that evade synthesis.

Interaction of Inorganic Nanoparticles With Cell Membranes

DTIC Science & Technology

2008-10-20

the field of colloidal and biological behaviour of nanoparticles. Questions regarding the colloidal behavior of particles in biological liquids...better the behaviour of nanoparticles in living systems. 2. Research work During the preparation phase of this project we have defined following...unique knowledge of the participating researgroups in the field of colloidal and biological behaviour of nanoparticles. Questions regarding the

Preparing the "New" Biologist of the Future: Student Research at the Interface of Mathematics and Biology

ERIC Educational Resources Information Center

Duncan, Sarah I.; Bishop, Pamela; Lenhart, Suzanne

2010-01-01

We describe a unique Research Experience for Undergraduates and Research Experience for Veterinary students summer program at the National Institute for Mathematical and Biological Synthesis on the campus of the University of Tennessee, Knoxville. The program focused on interdisciplinary research at the interface of biology and mathematics.…

Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

PubMed

Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

2004-06-11

An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

Diverse roles of integrin receptors in articular cartilage.

PubMed

Shakibaei, M; Csaki, C; Mobasheri, A

2008-01-01

Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

Molecularly organic/inorganic hybrid hollow mesoporous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality.

PubMed

Huang, Ping; Chen, Yu; Lin, Han; Yu, Luodan; Zhang, Linlin; Wang, Liying; Zhu, Yufang; Shi, Jianlin

2017-05-01

Based on the intrinsic features of high stability and unique multifunctionality, inorganic nanoparticles have shown remarkable potentials in combating cancer, but their biodegradability and biocompatibility are still under debate. As a paradigm, this work successfully demonstrates that framework organic-inorganic hybridization can endow the inorganic mesoporous silica nanocarriers with unique tumor-sensitive biodegradability and high biocompatibility. Based on a "chemical homology" mechanism, molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules (HMONs) with high dispersity and sub-50 nm particle dimension were constructed in mass production. A physiologically active disulfide bond (SS) was directly incorporated into the silica framework, which could break up upon contacting the reducing microenvironment of tumor tissue and biodegrade accordingly. Such a tumor-specific biodegradability is also responsible for the tumor-responsive drug releasing by the fast biodegradation and disintegration of the framework. The ultrasmall particle size of HMONs guarantees their high accumulation into tumor tissue, thus causing the high chemotherapeutic outcome. This research provides a paradigm that framework organic-inorganic hybridization can endow the inorganic nanocarrier with unique biological effects suitable for biomedical application, benefiting the development of novel nanosystems with the unique bio-functionality and performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry

PubMed Central

2016-01-01

Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is “tethering”—a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein–protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: “multifunctional scaffolding” versus “on-demand targeting”. By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms. PMID:26907082

On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry.

PubMed

Long, Marcus J C; Poganik, Jesse R; Aye, Yimon

2016-03-23

Proximity enhancement is a central chemical tenet underpinning an exciting suite of small-molecule toolsets that have allowed us to unravel many biological complexities. The leitmotif of this opus is "tethering"-a strategy in which a multifunctional small molecule serves as a template to bring proteins/biomolecules together. Scaffolding approaches have been powerfully applied to control diverse biological outcomes such as protein-protein association, protein stability, activity, and improve imaging capabilities. A new twist on this strategy has recently appeared, in which the small-molecule probe is engineered to unleash controlled amounts of reactive chemical signals within the microenvironment of a target protein. Modification of a specific target elicits a precisely timed and spatially controlled gain-of-function (or dominant loss-of-function) signaling response. Presented herein is a unique personal outlook conceptualizing the powerful proximity-enhanced chemical biology toolsets into two paradigms: "multifunctional scaffolding" versus "on-demand targeting". By addressing the latest advances and challenges in the established yet constantly evolving multifunctional scaffolding strategies as well as in the emerging on-demand precision targeting (and related) systems, this Perspective is aimed at choosing when it is best to employ each of the two strategies, with an emphasis toward further promoting novel applications and discoveries stemming from these innovative chemical biology platforms.

Activated Raf-1 causes growth arrest in human small cell lung cancer cells.

PubMed Central

Ravi, R K; Weber, E; McMahon, M; Williams, J R; Baylin, S; Mal, A; Harter, M L; Dillehay, L E; Claudio, P P; Giordano, A; Nelkin, B D; Mabry, M

1998-01-01

Small cell lung cancer (SCLC) accounts for 25% of all lung cancers, and is almost uniformly fatal. Unlike other lung cancers, ras mutations have not been reported in SCLC, suggesting that activation of ras-associated signal transduction pathways such as the raf-MEK mitogen-activated protein kinases (MAPK) are associated with biological consequences that are unique from other cancers. The biological effects of raf activation in small cell lung cancer cells was determined by transfecting NCI-H209 or NCI-H510 SCLC cells with a gene encoding a fusion protein consisting of an oncogenic form of human Raf-1 and the hormone binding domain of the estrogen receptor (DeltaRaf-1:ER), which can be activated with estradiol. DeltaRaf-1:ER activation resulted in phosphorylation of MAPK. Activation of this pathway caused a dramatic loss of soft agar cloning ability, suppression of growth capacity, associated with cell accumulation in G1 and G2, and S phase depletion. Raf activation in these SCLC cells was accompanied by a marked induction of the cyclin-dependent kinase (cdk) inhibitor p27(kip1), and a decrease in cdk2 protein kinase activities. Each of these events can be inhibited by pretreatment with the MEK inhibitor PD098059. These data demonstrate that MAPK activation by DeltaRaf-1:ER can activate growth inhibitory pathways leading to cell cycle arrest. These data suggest that raf/MEK/ MAPK pathway activation, rather than inhibition, may be a therapeutic target in SCLC and other neuroendocrine tumors. PMID:9421477

Mental representation of normal subjects about the sources of knowledge in different semantic categories and unique entities.

PubMed

Gainotti, Guido; Ciaraffa, Francesca; Silveri, Maria Caterina; Marra, Camillo

2009-11-01

According to the "sensory-motor model of semantic knowledge," different categories of knowledge differ for the weight that different "sources of knowledge" have in their representation. Our study aimed to evaluate this model, checking if subjective evaluations given by normal subjects confirm the different weight that various sources of knowledge have in the representation of different biological and artifact categories and of unique entities, such as famous people or monuments. Results showed that the visual properties are considered as the main source of knowledge for all the living and nonliving categories (as well as for unique entities), but that the clustering of these "sources of knowledge" is different for biological and artifacts categories. Visual data are, indeed, mainly associated with other perceptual (auditory, olfactory, gustatory, and tactual) attributes in the mental representation of living beings and unique entities, whereas they are associated with action-related properties and tactile information in the case of artifacts.

Synthetic Astrobiology

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Determination of Death: A Scientific Perspective on Biological Integration

PubMed Central

Condic, Maureen L.

2016-01-01

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., “life support”) that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. PMID:27075193

[Biology and immunotherapy advance of interleukin 2 and interleukin 15-review].

PubMed

Chen, Guang-Hua; Wu, De-Pei

2009-08-01

IL-2 and IL-15 play an important roles in regulating the lymphocyte function and homeostasis. Advances in understanding of the cellular and molecular biology of IL-2 and IL-15 and their receptor complex have provided rationale to better utilize them to expand and activate immune effectors in patients with cancer. These two cytokines stimulate similar responses from lymphocytes in vitro, but play markedly distinct roles in lymphoid biology in vivo. Their distinct physiological functions can be ascribed to distinct signaling pathways initiated by distinct cytokine receptor subunits, differential expression patterns of their receptors. Recently, the discovery of a novel mechanism of IL-15 cytokine signaling, trans-presentation, has provided insights into the divergent ways of these cytokine function. Although their heterotrimeric receptors have two receptor subunits in common, these two cytokines have contrasting roles in adaptive immune responses. The unique role of interleukin 2 is in the elimination of self-reactive T cells to prevent autoimmunity. By contrast, interleukin 15 is dedicated to the prolonged maintenance of memory T-cell responses to pathogens. As discussed in this article, the biology of IL-2 and IL-15 two cytokines will affect the development of novel treatment for malignancies and autoimmune diseases.

Identification of differentially expressed genes in Monochamus alternatus digested with azadirachtin.

PubMed

Lin, Tong; Liu, Qisi; Chen, Jingxiang

2016-09-15

The pine sawyer beetle Monochamus alternatus Hope, a major forest insect pest, is the primary vector of the destructive forest pest pine wood nematode, Bursaphelenchus xylophilus. Azadirachtin, an active compound of neem, is biologically interesting because it represents a group of important, successful botanical pesticides. We provide insight into the molecular effects of azadirachtin on M. alternatus at the transcriptional level to provide clues about possible molecular-level targets and to establish a link between azadirachtin and insect global responses. We found that 920 and 9894 unique genes were significantly up- and down-regulated, respectively. We obtained expression patterns of the differentially expressed genes (DEGs), identifying 4247, 3488 and 7613 sequences that involved cellular components, molecular functions and biological processes, respectively, and showed that the DEGs were distributed among 50 Gene Ontology categories. The Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were enriched in 50 pathways. Detailed gene profile knowledge of the interaction of azadirachtin with M. alternatus should facilitate the development of more effective azadirachtin-based products against M. alternatus and other target Coleoptera. These results further enhance the value of azadirachtin as a potential insecticide of biological origin, as well as for other biological applications.

Identification of differentially expressed genes in Monochamus alternatus digested with azadirachtin

PubMed Central

Lin, Tong; Liu, Qisi; Chen, Jingxiang

2016-01-01

The pine sawyer beetle Monochamus alternatus Hope, a major forest insect pest, is the primary vector of the destructive forest pest pine wood nematode, Bursaphelenchus xylophilus. Azadirachtin, an active compound of neem, is biologically interesting because it represents a group of important, successful botanical pesticides. We provide insight into the molecular effects of azadirachtin on M. alternatus at the transcriptional level to provide clues about possible molecular-level targets and to establish a link between azadirachtin and insect global responses. We found that 920 and 9894 unique genes were significantly up- and down-regulated, respectively. We obtained expression patterns of the differentially expressed genes (DEGs), identifying 4247, 3488 and 7613 sequences that involved cellular components, molecular functions and biological processes, respectively, and showed that the DEGs were distributed among 50 Gene Ontology categories. The Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were enriched in 50 pathways. Detailed gene profile knowledge of the interaction of azadirachtin with M. alternatus should facilitate the development of more effective azadirachtin-based products against M. alternatus and other target Coleoptera. These results further enhance the value of azadirachtin as a potential insecticide of biological origin, as well as for other biological applications. PMID:27629396

Biomedical and Catalytic Opportunities of Virus-Like Particles in Nanotechnology

PubMed Central

Schwarz, B.; Uchida, M.; Douglas, T.

2016-01-01

Within biology, molecules are arranged in hierarchical structures that coordinate and control the many processes that allow for complex organisms to exist. Proteins and other functional macromolecules are often studied outside their natural nanostructural context because it remains difficult to create controlled arrangements of proteins at this size scale. Viruses are elegantly simple nanosystems that exist at the interface of living organisms and nonliving biological machines. Studied and viewed primarily as pathogens to be combatted, viruses have emerged as models of structural efficiency at the nanoscale and have spurred the development of biomimetic nanoparticle systems. Virus-like particles (VLPs) are noninfectious protein cages derived from viruses or other cage-forming systems. VLPs provide incredibly regular scaffolds for building at the nanoscale. Composed of self-assembling protein subunits, VLPs provide both a model for studying materials’ assembly at the nanoscale and useful building blocks for materials design. The robustness and degree of understanding of many VLP structures allow for the ready use of these systems as versatile nanoparticle platforms for the conjugation of active molecules or as scaffolds for the structural organization of chemical processes. Lastly the prevalence of viruses in all domains of life has led to unique activities of VLPs in biological systems most notably the immune system. Here we discuss recent efforts to apply VLPs in a wide variety of applications with the aim of highlighting how the common structural elements of VLPs have led to their emergence as paradigms for the understanding and design of biological nanomaterials. PMID:28057256

Unique Monoclonal Antibody Recognizing the Third Extracellular Loop of CXCR4 Induces Lymphocyte Agglutination and Enhances Human Immunodeficiency Virus Type 1-Mediated Syncytium Formation and Productive Infection

PubMed Central

Tanaka, Reiko; Yoshida, Atsushi; Murakami, Tsutomu; Baba, Eishi; Lichtenfeld, Julliane; Omori, Takeru; Kimura, Tohru; Tsurutani, Naomi; Fujii, Nobutaka; Wang, Zi-Xuan; Peiper, Stephen C.; Yamamoto, Naoki; Tanaka, Yuetsu

2001-01-01

To increase insight into the structural basis of CXCR4 utilization in human immunodeficiency virus type 1 (HIV-1) infection, a new generation of three monoclonal antibodies (MAbs) was developed in WKA rats. The A80 MAb, which binds an epitope in the third extracellular loop (ECL3) of CXCR4, has unique biologic properties that provide novel insights into CXCR4 function. This agent enhanced syncytium formation in activated human peripheral blood mononuclear cells (PBMC) infected with X4 or R5 and CEM cells infected with X4 HIV-1 strains. Exposure to A80 increased the productive infection of activated CD4+ T cells and CEM cells with R5 and X4 viruses, respectively. This antibody uniquely induced agglutination of PBMC and CEM cells but did not activate calcium mobilization. Agglutination induced by A80 was inhibited by stromal cell-derived factor 1, T22, and phorbol 12-myristate 13-acetate but was not significantly altered by pretreatment of cells with pertussis toxin, wortmannin, or MAbs to LFA-1, ICAM-1, ICAM-2, and ICAM-3. The binding of the A145 and A120 MAbs was mapped to the N-terminal extracellular domain and a conformational epitope involving ECL1 and ECL2, respectively. Both of these MAbs inhibited HIV-1 infection and lacked the novel properties of A80. These results suggest a new role for CXCR4 in homologous lymphocyte adhesion that is ligand independent and in HIV-1 infection. PMID:11689635

An Intervention to Reduce Psychosocial and Biological Indicators of Stress in African American Lupus Patients: The Balancing Lupus Experiences with Stress Strategies Study.

PubMed

Williams, Edith M; Penfield, Megan; Kamen, Diane; Oates, James C

2014-01-01

Very little is known about the impact of psychosocial stress on African American lupus patients. Due to the exposure of African Americans to a unique trajectory of stressors throughout life, it may be critical to understand the relationship between psychosocial stress and underlying biological mechanisms that influence disease activity and pathology in this high risk group. The Balancing Lupus Experiences with Stress Strategies (BLESS) study piloted the validated "Better Choices, Better Health" Chronic Disease Self-Management Program (CDSMP) in 30 African-American lupus patients participating in the SLE Clinic Database Project at the Medical University of South Carolina (MUSC). Measures of psychosocial and biological indicators of stress were collected in all of the patients in each of the study conditions before and after intervention activities, as well as four months post-intervention, to assess the effectiveness of the program in reducing perceived and biological indicators of stress. Participation in the workshops had large effects upon depression ( d =1.63 and d = 1.68), social/role activities limitations ( d =1.15), health distress ( d =1.13 and d = 0.78), fatigue ( d =1.03), pain ( d =0.96), and lupus self-efficacy ( d =0.85). Neither the differences in cortisol or DHEA levels pre- and post-intervention were found to be significantly different between intervention participants and controls. The intervention workshops acted to reduce perceived stress and improve quality of life. Our findings imply that comparable, if not more significant gains in relevant health indicators are possible in African American patients when provided the opportunity to participate in CDSMP's.

Zinc activates damage-sensing TRPA1 ion channels.

PubMed

Hu, Hongzhen; Bandell, Michael; Petrus, Matt J; Zhu, Michael X; Patapoutian, Ardem

2009-03-01

Zinc is an essential biological trace element. It is required for the structure or function of over 300 proteins, and it is increasingly recognized for its role in cell signaling. However, high concentrations of zinc have cytotoxic effects, and overexposure to zinc can cause pain and inflammation through unknown mechanisms. Here we show that zinc excites nociceptive somatosensory neurons and causes nociception in mice through TRPA1, a cation channel previously shown to mediate the pungency of wasabi and cinnamon through cysteine modification. Zinc activates TRPA1 through a unique mechanism that requires zinc influx through TRPA1 channels and subsequent activation via specific intracellular cysteine and histidine residues. TRPA1 is highly sensitive to intracellular zinc, as low nanomolar concentrations activate TRPA1 and modulate its sensitivity. These findings identify TRPA1 as an important target for the sensory effects of zinc and support an emerging role for zinc as a signaling molecule that can modulate sensory transmission.

Lactimidomycin, Iso-migrastatin and Related Glutarimide-containing 12-membered Macrolides are Extremely Potent Inhibitors of Cell Migration

PubMed Central

Ju, Jianhua; Rajski, Scott R.; Lim, Si-Kyu; Seo, Jeong-Woo; Peters, Noël R.; Hoffmann, F. Michael; Shen, Ben

2009-01-01

Migrastatin (1), iso-migrastatin (5) and lactimidomycin (7) are all glutarimide-containing polyketides known for their unique structures and cytotoxic activities against human cancer cell lines. Migrastatin, a strong inhibitor of tumor cell migration, has been an important lead in the development of antimetastatic agents. Yet studies of the related 12-membered macrolides iso-migrastatin, lactimidomycin and related analogs have been hampered by their limited availability. We report here the production, isolation, structural characterization and biological activities of iso-migrastatin, lactimidomycin, and 23 related congeners. Our studies showed that, as a family, the glutarimide-containing 12-membered macrolides are extremely potent cell migration inhibitors with some members displaying activity on par or superior to that of migrastatin as exemplified by compounds 5, 7, and 9–12. On the basis of these findings, the structures and activity of this family of compounds as cell migration inhibitors are discussed. PMID:19132897

Drosophila melanogaster--the model organism of choice for the complex biology of multi-cellular organisms

NASA Technical Reports Server (NTRS)

Beckingham, Kathleen M.; Armstrong, J. Douglas; Texada, Michael J.; Munjaal, Ravi; Baker, Dean A.

2005-01-01

Drosophila melanogaster has been intensely studied for almost 100 years. The sophisticated array of genetic and molecular tools that have evolved for analysis of gene function in this organism are unique. Further, Drosophila is a complex multi-cellular organism in which many aspects of development and behavior parallel those in human beings. These combined advantages have permitted research in Drosophila to make seminal contributions to the understanding of fundamental biological processes and ensure that Drosophila will continue to provide unique insights in the genomic era. An overview of the genetic methodologies available in Drosophila is given here, together with examples of outstanding recent contributions of Drosophila to our understanding of cell and organismal biology. The growing contribution of Drosophila to our knowledge of gravity-related responses is addressed.

Immunologic responses to therapeutic biologic agents.

PubMed

Purcell, R T; Lockey, R F

2008-01-01

Recombinant protein technology and the subsequent development of biologic agents for pharmacotherapy have greatly improved the treatment of a wide variety of diseases in humans. These products are subject to reactions not previously seen in other drug classes. Additionally, subtle alteration in the manufacture or administration of a biologic agent may cause reactions in subjects who previously tolerated it. This review highlights the unique immunologic reactions that are associated with the more commonly used biologic agents.

Inquiry-based examination of chemical disruption of bacterial biofilms.

PubMed

Redelman, Carly V; Hawkins, Misty A W; Drumwright, Franklin R; Ransdell, Beverly; Marrs, Kathleen; Anderson, Gregory G

2012-01-01

Inquiry-based instruction in the sciences has been demonstrated as a successful educational strategy to use for both high school and college science classrooms. As participants in the NSF Graduate STEM Fellows in K-12 Education (GK-12) Program, we were tasked with creating novel inquiry-based activities for high school classrooms. As a way to introduce microbiology, molecular biology, ecology, and human health to students, we created a laboratory activity involving formation of biofilms composed of environmental bacteria from pond water and investigation into the resistance of these biofilms to antimicrobial agents. Two high schools participated in this study in different ways. Pike High School biology and advanced environmental science classrooms obtained pond water samples and grew biofilms from the bacteria in the pond water on plastic plates. They also observed killing of these biofilms by common household antimicrobial agents. As a senior capstone project, students at Arsenal Technical High School built on these research findings by isolating two different bacterial strains from the pond water and demonstrating the stimulatory effect of ethanol on biofilms formed by isolated bacterial strains. These activities were successful at introducing complex biological topics to high school students in a unique and exciting way. The students scored significantly higher on postactivity surveys compared with preactivity surveys that measured microbiology knowledge and experimental design knowledge. Furthermore, these projects seemed to elicit an excitement for science in the students who participated. Copyright © 2012 Wiley Periodicals, Inc.

Investigating bioconjugation by atomic force microscopy

PubMed Central

2013-01-01

Nanotechnological applications increasingly exploit the selectivity and processivity of biological molecules. Integration of biomolecules such as proteins or DNA into nano-systems typically requires their conjugation to surfaces, for example of carbon-nanotubes or fluorescent quantum dots. The bioconjugated nanostructures exploit the unique strengths of both their biological and nanoparticle components and are used in diverse, future oriented research areas ranging from nanoelectronics to biosensing and nanomedicine. Atomic force microscopy imaging provides valuable, direct insight for the evaluation of different conjugation approaches at the level of the individual molecules. Recent technical advances have enabled high speed imaging by AFM supporting time resolutions sufficient to follow conformational changes of intricately assembled nanostructures in solution. In addition, integration of AFM with different spectroscopic and imaging approaches provides an enhanced level of information on the investigated sample. Furthermore, the AFM itself can serve as an active tool for the assembly of nanostructures based on bioconjugation. AFM is hence a major workhorse in nanotechnology; it is a powerful tool for the structural investigation of bioconjugation and bioconjugation-induced effects as well as the simultaneous active assembly and analysis of bioconjugation-based nanostructures. PMID:23855448

Investigating bioconjugation by atomic force microscopy.

PubMed

Tessmer, Ingrid; Kaur, Parminder; Lin, Jiangguo; Wang, Hong

2013-07-15

Nanotechnological applications increasingly exploit the selectivity and processivity of biological molecules. Integration of biomolecules such as proteins or DNA into nano-systems typically requires their conjugation to surfaces, for example of carbon-nanotubes or fluorescent quantum dots. The bioconjugated nanostructures exploit the unique strengths of both their biological and nanoparticle components and are used in diverse, future oriented research areas ranging from nanoelectronics to biosensing and nanomedicine. Atomic force microscopy imaging provides valuable, direct insight for the evaluation of different conjugation approaches at the level of the individual molecules. Recent technical advances have enabled high speed imaging by AFM supporting time resolutions sufficient to follow conformational changes of intricately assembled nanostructures in solution. In addition, integration of AFM with different spectroscopic and imaging approaches provides an enhanced level of information on the investigated sample. Furthermore, the AFM itself can serve as an active tool for the assembly of nanostructures based on bioconjugation. AFM is hence a major workhorse in nanotechnology; it is a powerful tool for the structural investigation of bioconjugation and bioconjugation-induced effects as well as the simultaneous active assembly and analysis of bioconjugation-based nanostructures.

Cancer Registries and Monitoring the Impact of Prophylactic Human Papillomavirus Vaccines: The Potential Role

PubMed Central

Saraiya, Mona; Goodman, Marc T.; Datta, S. Deblina; Chen, Vivien W.; Wingo, Phyllis A.

2009-01-01

The recent US Food and Drug Administration licensure of a prophylactic vaccine against oncogenic human papillomavirus (HPV) types 16 and 18, the first of its kind, poses unique challenges in postmarketing vaccine surveillance, especially in measuring vaccine effectiveness against biologic endpoints of HPV infection. Historically, the national system of population-based cancer registries in the US has provided high-quality data on cancer incidence and mortality for the most important biologic endpoints, namely, anogenital cancers and some oral cavity/oropharyngeal cancers. There also has been some data collection on cancer precursors; however, this activity has been inconsistent and of lower priority. Because effectiveness against HPV-associated cancers will not be measurable for several decades, strengthening and possibly expanding the capacity of registries to collect precancer data, which are earlier manifestations of infection, must be considered. Collecting type-specific data on HPV-associated precancers and cancers. While keeping in mind the current limitations of registry operations, they discuss resources that may be needed to implement and sustain these types of activities. PMID:18980287

Deubiquitinating enzyme regulation of the p53 pathway: A lesson from Otub1

PubMed Central

Sun, Xiao-Xin; Dai, Mu-Shui

2014-01-01

Deubiquitination has emerged as an important mechanism of p53 regulation. A number of deubiquitinating enzymes (DUBs) from the ubiquitin-specific protease family have been shown to regulate the p53-MDM2-MDMX networks. We recently reported that Otub1, a DUB from the OTU-domain containing protease family, is a novel p53 regulator. Interestingly, Otub1 abrogates p53 ubiquitination and stabilizes and activates p53 in cells independently of its deubiquitinating enzyme activity. Instead, it does so by inhibiting the MDM2 cognate ubiquitin-conjugating enzyme (E2) UbcH5. Otub1 also regulates other biological signaling through this non-canonical mechanism, suppression of E2, including the inhibition of DNA-damage-induced chromatin ubiquitination. Thus, Otub1 evolves as a unique DUB that mainly suppresses E2 to regulate substrates. Here we review the current progress made towards the understanding of the complex regulation of the p53 tumor suppressor pathway by DUBs, the biological function of Otub1 including its positive regulation of p53, and the mechanistic insights into how Otub1 suppresses E2. PMID:24920999

[Anti-epidermal growth factor receptor treatment: a new paradigm for conducting therapeutic trials].

PubMed

Marty, Michel; Bedairia, Naima; Armand, Jean-Pierre

2003-11-01

Agents which modify biological properties of tumour tissue can target many tenths of functions over- or underexpressed in human tumours. In general these agents are cytostatic rather than cytotoxic and will affect only that fraction of human tumours where the target plays and important and unique role for the viability of the tumour tissue. Alternatively it is expected that acute toxicity will not be observed at active dose-time exposure; rather subacute or chronic toxicity can be observed with these agents. Clinical studies will have to follow the following rules: characterisation of the pharmacological target and of its functional role on tumour tissue; definition of an optimal biological dose rather than a maximum tolerated dose; importance of validated pharmacodynamic endpoints; importance and thus need for early studies of combination regimens. It is still too early to define general guidelines for the study of these different therapeutic families. Nevertheless, studies already conducted with agents interfering with EGF mediated signalization have already permitted preliminary indications on pharmacodynamics, target assessment, level of activity and conduct of clinical trials with combination regimens.

PANDORA: keyword-based analysis of protein sets by integration of annotation sources.

PubMed

Kaplan, Noam; Vaaknin, Avishay; Linial, Michal

2003-10-01

Recent advances in high-throughput methods and the application of computational tools for automatic classification of proteins have made it possible to carry out large-scale proteomic analyses. Biological analysis and interpretation of sets of proteins is a time-consuming undertaking carried out manually by experts. We have developed PANDORA (Protein ANnotation Diagram ORiented Analysis), a web-based tool that provides an automatic representation of the biological knowledge associated with any set of proteins. PANDORA uses a unique approach of keyword-based graphical analysis that focuses on detecting subsets of proteins that share unique biological properties and the intersections of such sets. PANDORA currently supports SwissProt keywords, NCBI Taxonomy, InterPro entries and the hierarchical classification terms from ENZYME, SCOP and GO databases. The integrated study of several annotation sources simultaneously allows a representation of biological relations of structure, function, cellular location, taxonomy, domains and motifs. PANDORA is also integrated into the ProtoNet system, thus allowing testing thousands of automatically generated clusters. We illustrate how PANDORA enhances the biological understanding of large, non-uniform sets of proteins originating from experimental and computational sources, without the need for prior biological knowledge on individual proteins.

Variations in protein/flavin hydrogen bonding in a LOV domain produce non-Arrhenius kinetics of adduct decay†

PubMed Central

Zoltowski, Brian D.; Nash, Abigail I.; Gardner, Kevin H.

2011-01-01

Light Oxygen Voltage (LOV) domains utilize a conserved blue light-dependent mechanism to control a diverse array of effector domains in biological and engineered proteins. Variations in the kinetics and efficiency of LOV photochemistry fine tune various aspects of the photic response. Characterization of the kinetics of a key aspect of this photochemical mechanism in EL222, a blue-light responsive DNA binding protein from Erythrobacter litoralis HTCC2594, reveals unique non-Arrhenius behavior in the rate of dark state cleavage of the photochemically-generated adduct. Sequence analysis and mutagenesis studies establish that this effect stems from a Gln to Ala mutation unique to EL222 and homologous proteins from marine bacteria. Kinetic and spectroscopic analyses reveal that hydrogen bonding interactions between the FMN N1, O2 and ribityl hydroxyls with the surrounding protein regulate photocycle kinetics and stabilize the LOV active site from temperature-induced alteration in local structure. Substitution of residues interacting with the N1-O2 locus modulates adduct stability, structural flexibility and sequestration of the active site from bulk solvent without perturbation of light-activated DNA binding. Together, these variants link non-Arrhenius behavior to specific alteration of an H-bonding network, while affording tunability of photocycle kinetics. PMID:21923139

Variations in protein-flavin hydrogen bonding in a light, oxygen, voltage domain produce non-Arrhenius kinetics of adduct decay.

PubMed

Zoltowski, Brian D; Nash, Abigail I; Gardner, Kevin H

2011-10-18

Light, oxygen, voltage (LOV) domains utilize a conserved blue light-dependent mechanism to control a diverse array of effector domains in biological and engineered proteins. Variations in the kinetics and efficiency of LOV photochemistry fine-tune various aspects of the photic response. Characterization of the kinetics of a key aspect of this photochemical mechanism in EL222, a blue light responsive DNA binding protein from Erythrobacter litoralis HTCC2594, reveals unique non-Arrhenius behavior in the rate of dark-state cleavage of the photochemically generated adduct. Sequence analysis and mutagenesis studies establish that this effect stems from a Gln to Ala mutation unique to EL222 and homologous proteins from marine bacteria. Kinetic and spectroscopic analyses reveal that hydrogen bonding interactions between the FMN N1, O2, and ribityl hydroxyls and the surrounding protein regulate photocycle kinetics and stabilize the LOV active site from temperature-induced alteration in local structure. Substitution of residues interacting with the N1-O2 locus modulates adduct stability, structural flexibility, and sequestration of the active site from bulk solvent without perturbation of light-activated DNA binding. Together, these variants link non-Arrhenius behavior to specific alteration of an H-bonding network, while affording tunability of photocycle kinetics. © 2011 American Chemical Society

Tallow amphopolycarboxyglycinate-stabilized silver nanoparticles: new frontiers in development of plant protection products with a broad spectrum of action against phytopathogens

NASA Astrophysics Data System (ADS)

Krutyakov, Yurii A.; Kudrinskiy, Alexey A.; Zherebin, Pavel M.; Yapryntsev, Alexey D.; Pobedinskaya, Marina A.; Elansky, Sergey N.; Denisov, Albert N.; Mikhaylov, Dmitry M.; Lisichkin, Georgii V.

2016-07-01

Sustainable agriculture calls for minimal use of agrochemicals in order to protect the environment. It has caused an increase in the rate of nanoparticles use, in particular silver nanoparticles (AgNPs) due to their safety for mammals, unique biological activity and a broad spectrum of action against fungal and bacterial pathogens. Until now the use of AgNPs dispersions in the agricultural sector has been essentially limited due to many factors decreased their stability (mixing with other pesticides, presence of electrolytes). We present a versatile synthesis of polyampholyte surfactant (tallow amphopolycarboxyglycinate) stabilized AgNPs. We took a close look at unique aggregation behavior (via dynamic light scattering and UV-vis spectroscopy) and biocidal activity of obtained silver colloids. AgNPs are characterized by exclusively high aggregative stability in the presence of coagulating agents NaNO3 and NaSO4 (up to 1 M), during drying/redispergation, and frost/defrost cycles. The dispersion of AgNPs shows high biocidal activity (EC50 is ten times lower than commercial species ones) with respect to Phytophthora infestans and phytopathogenic fungi. This points to the possibility of successful application of silver preparations within agriculture with the goal of partial reduction of the use of toxic and expensive synthetic antibiotics and pesticides.

Biochemical Regulatory Features of Activation-Induced Cytidine Deaminase Remain Conserved from Lampreys to Humans

PubMed Central

King, Justin J.; Amemiya, Chris T.; Hsu, Ellen

2017-01-01

ABSTRACT Activation-induced cytidine deaminase (AID) is a genome-mutating enzyme that initiates class switch recombination and somatic hypermutation of antibodies in jawed vertebrates. We previously described the biochemical properties of human AID and found that it is an unusual enzyme in that it exhibits binding affinities for its substrate DNA and catalytic rates several orders of magnitude higher and lower, respectively, than a typical enzyme. Recently, we solved the functional structure of AID and demonstrated that these properties are due to nonspecific DNA binding on its surface, along with a catalytic pocket that predominantly assumes a closed conformation. Here we investigated the biochemical properties of AID from a sea lamprey, nurse shark, tetraodon, and coelacanth: representative species chosen because their lineages diverged at the earliest critical junctures in evolution of adaptive immunity. We found that these earliest-diverged AID orthologs are active cytidine deaminases that exhibit unique substrate specificities and thermosensitivities. Significant amino acid sequence divergence among these AID orthologs is predicted to manifest as notable structural differences. However, despite major differences in sequence specificities, thermosensitivities, and structural features, all orthologs share the unusually high DNA binding affinities and low catalytic rates. This absolute conservation is evidence for biological significance of these unique biochemical properties. PMID:28716949

The iPlant collaborative: cyberinfrastructure for plant biology

USDA-ARS?s Scientific Manuscript database

The iPlant Collaborative (iPlant) is a United States National Science Foundation (NSF)funded project that aims to create an innovative, comprehensive, and foundational cyberinfrastructure in support of plant biology research (PSCIC, 2006). iPlant is developing cyberinfrastructure that uniquely enabl...

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

PubMed

D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

2011-02-01

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Bioactive Oligosaccharide Natural Products

PubMed Central

McCranie, Emilianne K.; Bachmann, Brian O.

2016-01-01

Oligosaccharide natural products target a wide spectrum of biological processes including disruption of cell wall biosynthesis, interference of bacterial translation, and inhibition of human α-amylase. Correspondingly, oligosaccharides possess potential for development as treatments of such diverse diseases as bacterial infections and type II diabetes. Despite their potent and selective activities and potential clinical relevance, isolated bioactive secondary metabolic oligosaccharides are less prevalent than other classes of natural products and their biosynthesis has received comparatively less attention. This review highlights the unique modes of action and biosynthesis of four classes of bioactive oligosaccharides: the orthosomycins, moenomycins, saccharomicins, and acarviostatins. PMID:24883430

A simple fragment of cyclic acyldepsipeptides is necessary and sufficient for ClpP activation and antibacterial activity.

PubMed

Carney, Daniel W; Compton, Corey L; Schmitz, Karl R; Stevens, Julia P; Sauer, Robert T; Sello, Jason K

2014-10-13

The development of new antibacterial agents, particularly those with unique biological targets, is essential to keep pace with the inevitable emergence of drug resistance in pathogenic bacteria. We identified the minimal structural component of the cyclic acyldepsipeptide (ADEP) antibiotics that exhibits antibacterial activity. We found that N-acyldifluorophenylalanine fragments function via the same mechanism of action as ADEPs, as evidenced by the requirement of ClpP for the fragments' antibacterial activity, the ability of fragments to activate Bacillus subtilis ClpP in vitro, and the capacity of an N-acyldifluorophenylalanine affinity matrix to capture ClpP from B. subtilis cell lysates. N-acyldifluorophenylalanine fragments are much simpler in structure than the full ADEPs and are also highly amenable to structural diversification. Thus, the stage has been set for the development of non-peptide activators of ClpP that can be used as antibacterial agents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neonicotinoid insecticides: highlights of a symposium on strategic molecular designs.

PubMed

Tomizawa, Motohiro; Casida, John E

2011-04-13

Neonicotinoids are the newest of the five major classes of insecticides (the others are chlorinated hydrocarbons, organophosphorus compounds, methylcarbamates, and pyrethroids), and they make up approximately one-fourth of the world insecticide market. Nithiazine was the lead compound from Shell Development Co. in California later optimized by Shinzo Kagabu of Nihon Tokushu Noyaku Seizo to increase the potency and photostability, resulting in imidacloprid and thiacloprid. These discoveries are the basis for the International Award for Research in Agrochemicals of the American Chemical Society presented in 2010 to Professor Shinzo Kagabu. Five other neonicotinoids were added by others for the current set of seven commercial compounds. This symposium considers the progress in discovery and development of novel chemotype nicotinic insecticides with enhanced effectiveness, unique biological properties, and maximal safety. Chemorational approaches considered include physicochemical properties, metabolic activation and detoxification, and chemical and structural biology aspects potentially facilitating receptor structure-guided insecticide design.

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

PubMed Central

Crane, Erika A.

2016-01-01

Abstract Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID:26833854

Microfibril-associated glycoproteins MAGP-1 and MAGP-2 in disease.

PubMed

Craft, Clarissa S; Broekelmann, Thomas J; Mecham, Robert P

2018-03-07

Microfibril-associated glycoproteins 1 and 2 (MAGP-1, MAGP-2) are protein components of extracellular matrix microfibrils. These proteins interact with fibrillin, the core component of microfibrils, and impart unique biological properties that influence microfibril function in vertebrates. MAGPs bind active forms of TGFβ and BMPs and are capable of modulating Notch signaling. Mutations in MAGP-1 or MAGP-2 have been linked to thoracic aneurysms and metabolic disease in humans. MAGP-2 has also been shown to be an important biomarker in several human cancers. Mice lacking MAGP-1 or MAGP-2 have defects in multiple organ systems, which reflects the widespread distribution of microfibrils in vertebrate tissues. This review summarizes our current understanding of the function of the MAGPs and their relationship to human disease. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

The alphabet of intrinsic disorder

PubMed Central

Theillet, Francois-Xavier; Kalmar, Lajos; Tompa, Peter; Han, Kyou-Hoon; Selenko, Philipp; Dunker, A. Keith; Daughdrill, Gary W.; Uversky, Vladimir N

2013-01-01

A significant fraction of every proteome is occupied by biologically active proteins that do not form unique three-dimensional structures. These intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) have essential biological functions and are characterized by extensive structural plasticity. Such structural and functional behavior is encoded in the amino acid sequences of IDPs/IDPRs, which are enriched in disorder-promoting residues and depleted in order-promoting residues. In fact, amino acid residues can be arranged according to their disorder-promoting tendency to form an alphabet of intrinsic disorder that defines the structural complexity and diversity of IDPs/IDPRs. This review is the first in a series of publications dedicated to the roles that different amino acid residues play in defining the phenomenon of protein intrinsic disorder. We start with proline because data suggests that of the 20 common amino acid residues, this one is the most disorder-promoting. PMID:28516008

Microfluidics and Coagulation Biology

PubMed Central

Colace, Thomas V.; Tormoen, Garth W.

2014-01-01

The study of blood ex vivo can occur in closed or open systems, with or without flow. Microfluidic devices facilitate measurements of platelet function, coagulation biology, cellular biorheology, adhesion dynamics, pharmacology, and clinical diagnostics. An experimental session can accommodate 100s to 1000s of unique clotting events. Using microfluidics, thrombotic events can be studied on defined surfaces of biopolymers, matrix proteins, and tissue factor under constant flow rate or constant pressure drop conditions. Distinct shear rates can be created on a device with a single perfusion pump. Microfluidic devices facilitated the determination of intraluminal thrombus permeability and the discovery that platelet contractility can be activated by a sudden decrease in flow. Microfluidics are ideal for multicolor imaging of platelets, fibrin, and phosphatidylserine and provide a human blood analog to the mouse injury models. Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics. PMID:23642241

Using NMR chemical shifts to calculate the propensity for structural order and disorder in proteins.

PubMed

Tamiola, Kamil; Mulder, Frans A A

2012-10-01

NMR spectroscopy offers the unique possibility to relate the structural propensities of disordered proteins and loop segments of folded peptides to biological function and aggregation behaviour. Backbone chemical shifts are ideally suited for this task, provided that appropriate reference data are available and idiosyncratic sensitivity of backbone chemical shifts to structural information is treated in a sensible manner. In the present paper, we describe methods to detect structural protein changes from chemical shifts, and present an online tool [ncSPC (neighbour-corrected Structural Propensity Calculator)], which unites aspects of several current approaches. Examples of structural propensity calculations are given for two well-characterized systems, namely the binding of α-synuclein to micelles and light activation of photoactive yellow protein. These examples spotlight the great power of NMR chemical shift analysis for the quantitative assessment of protein disorder at the atomic level, and further our understanding of biologically important problems.

Tau Kinetics in Neurons and the Human Central Nervous System.

PubMed

Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G; Patterson, Bruce W; Gordon, Brian A; Jockel-Balsarotti, Jennifer; Sullivan, Melissa; Crisp, Matthew J; Kasten, Tom; Kirmess, Kristopher M; Kanaan, Nicholas M; Yarasheski, Kevin E; Baker-Nigh, Alaina; Benzinger, Tammie L S; Miller, Timothy M; Karch, Celeste M; Bateman, Randall J

2018-03-21

We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities. The half-life of tau in control human iPSC-derived neurons is 6.74 ± 0.45 days and in human CNS is 23 ± 6.4 days. In cognitively normal and Alzheimer's disease participants, the production rate of tau positively correlates with the amount of amyloid plaques, indicating a biological link between amyloid plaques and tau physiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Energy coding in biological neural networks

PubMed Central

Zhang, Zhikang

2007-01-01

According to the experimental result of signal transmission and neuronal energetic demands being tightly coupled to information coding in the cerebral cortex, we present a brand new scientific theory that offers an unique mechanism for brain information processing. We demonstrate that the neural coding produced by the activity of the brain is well described by our theory of energy coding. Due to the energy coding model’s ability to reveal mechanisms of brain information processing based upon known biophysical properties, we can not only reproduce various experimental results of neuro-electrophysiology, but also quantitatively explain the recent experimental results from neuroscientists at Yale University by means of the principle of energy coding. Due to the theory of energy coding to bridge the gap between functional connections within a biological neural network and energetic consumption, we estimate that the theory has very important consequences for quantitative research of cognitive function. PMID:19003513

State of research: environmental pathways and food chain transfer.

PubMed Central

Vaughan, B E

1984-01-01

Data on the chemistry of biologically active components of petroleum, synthetic fuel oils, certain metal elements and pesticides provide valuable generic information needed for predicting the long-term fate of buried waste constituents and their likelihood of entering food chains. Components of such complex mixtures partition between solid and solution phases, influencing their mobility, volatility and susceptibility to microbial transformation. Estimating health hazards from indirect exposures to organic chemicals involves an ecosystem's approach to understanding the unique behavior of complex mixtures. Metabolism by microbial organisms fundamentally alters these complex mixtures as they move through food chains. Pathway modeling of organic chemicals must consider the nature and magnitude of food chain transfers to predict biological risk where metabolites may become more toxic than the parent compound. To obtain predictions, major areas are identified where data acquisition is essential to extend our radiological modeling experience to the field of organic chemical contamination. PMID:6428875

50 CFR 223.203 - Anadromous fish.

Code of Federal Regulations, 2011 CFR

2011-10-01

... identifiably unique biological and life history traits. Populations may be aggregated for management purposes... units, describe how the management units are defined, given biological and life history traits, so as to... impacts. (E) Provide for effective monitoring and adaptive management. (F) Use the best available science...

Protecting endangered species under future climate change: From single-species preservation to an anticipatory policy approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloomgarden, C.A.

1995-09-01

Anthropogenic climate change presents a unique challenge for endangered species policy and an opportunity for policy makers to develop a more predictive and robust approach to preserving the nation`s biological resources. Biological and ecological reactions to shifting climate conditions and the potential feedbacks and synergistic effects of such changes may threaten the well-being of many species, particularly of those already in jeopardy of extinction. The United States Endangered Species Act of 1973 will fail to keep pace with increasing numbers of species needing protection as long as it remains focused on protecting species individually. The act must not be abandoned,more » however; it holds tremendous promise for preserving biological diversity through a more proactive, anticipatory perspective. The current Endangered Species Act should be reinforced and improved by better integration of scientific expertise into habitat and community preservation listing decisions and recovery plan development. Given the uncertainties surrounding long-term environmental consequences of human activities and resource use, a longer-term perspective must be integrated into all efforts to protect our biotic resources. 55 refs.« less

Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein,more » we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.« less

Protecting endangered species under future climate change: From single-species preservation to an anticipatory policy approach

NASA Astrophysics Data System (ADS)

Bloomgarden, Carol A.

1995-09-01

Anthropogenic climate climate change presents a unique challenge for endangered species policy and an opportunity for policy makers to develop a more predictive and robust approach to preserving the nation's biological resources. Biological and ecological reactions to shifting climate conditions and the potential feedbacks and synergistic effects of such changes may threaten the well-being of many species, particularly of those already in jeopardy of extinction. The United States Endangered Species Act of 1973 will fail to keep pace with increasing numbers of species needing protection as long as it remains focused on protecting species individually. The act must not be abandoned, however; it holds tremendous promise for preserving biological diversity through a more proactive, anticipatory perspective. The current Endangered Species Act should be reinforced and improved by better integration of scientific expertise into habitat and community preservation listing decisions and recovery plan devlopment. Given the uncertainties surrounding long-term environmental consequences of human activities and resource use, a longer-term perspective must be integrated into all efforts to protect our biotic resources.

Graphene liquid cells for multi-technique analysis of biological cells in water environment

NASA Astrophysics Data System (ADS)

Matruglio, A.; Zucchiatti, P.; Birarda, G.; Marmiroli, B.; D'Amico, F.; Kocabas, C.; Kiskinova, M.; Vaccari, L.

2018-05-01

In-cell exploration of biomolecular constituents is the new frontier of cellular biology that will allow full access to structure-activity correlation of biomolecules, overcoming the limitations imposed by dissecting the cellular milieu. However, the presence of water, which is a very strong IR absorber and incompatible with the vacuum working conditions of all analytical methods using soft x-rays and electrons, poses severe constraint to perform important imaging and spectroscopic analyses under physiological conditions. Recent advances to separate the sample compartment in liquid cell are based on electron and photon transparent but molecular-impermeable graphene membranes. This strategy has opened a unique opportunity to explore technological materials under realistic operation conditions using various types of electron microscopy. However, the widespread of the graphene liquid cell applications is still impeded by the lack of well-established approaches for their massive production. We report on the first preliminary results for the fabrication of reproducible graphene liquid cells appropriate for the analysis of biological specimens in their natural hydrated environment with several crucial analytical techniques, namely FTIR microscopy, Raman spectroscopy, AFM, SEM and TEM.

The Thermochemical and Kinetic Properties of Ascorbate are Tuned by its Local Environment: Solution Chemistry and Biochemical Implications

PubMed Central

Warren, Jeffrey J.; Mayer, James M.

2010-01-01

Ascorbate (Vitamin C) is a ubiquitous biological cofactor. While its aqueous solution chemistry has long been studied, many in vivo reactions of ascorbate occur in enzyme active sites or at membrane interfaces, which have varying local environments. This report shows that the rate and driving force of oxidations of two ascorbate derivatives by the TEMPO radical (2,2′-6,6′-tetramethylpiperidine-1-oxyl) in acetonitrile are very sensitive to the presence of various additives. These reactions proceed by the transfer of a proton and an electron (a hydrogen atom), as is typical of biological ascorbate reactions. The measured rate and equilibrium constants vary substantially with added water or other polar solutes in acetonitrile solutions, indicating large shifts in the reducing power of ascorbate. The correlation of rate and equilibrium constants indicates that this effect has a thermochemical origin rather than being a purely kinetic effect. This contrasts with previous examples of solvent effects on hydrogen atom transfer reactions. Potential biological implications of this apparently unique effect are discussed. PMID:20476757

ACE Inhibitory and Antioxidant Activities of Collagen Hydrolysates from the Ribbon Jellyfish (Chrysaora sp.).

PubMed

Barzideh, Zoha; Latiff, Aishah Abd; Gan, Chee-Yuen; Abedin, Md Zainul; Alias, Abd Karim

2014-12-01

Collagen isolated from the ribbon jellyfish ( Chrysaora sp.) was hydrolysed using three different proteases ( i.e. trypsin, alcalase and Protamex) to obtain bioactive peptides. Angiotensin-I-converting enzyme (ACE) inhibitory activity and antioxidant activities ( i.e. ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity) of the peptides were measured and compared, and the effect of the duration of hydrolysis on the bioactivity (ACE inhibitory and antioxidant activities) of peptides was also evaluated. FRAP activity was the highest in Protamex-induced (25-27 mM) and trypsin-induced hydrolysates (24-26 mM) at 7 and 9 h, respectively. Conversely, hydrolysates produced by trypsin for 1 and 3 h showed the highest DPPH radical scavenging activities (94 and 92%, respectively). Trypsin-induced hydrolysates (at 3 h) also showed the highest ACE inhibitory activity (89%). The peptide sequences with the highest activities were identified using tandem mass spectrometry, and the results show that the hydrolysates had a high content of hydrophobic amino acids as well as unique amino acid sequences, which likely contribute to their biological activities.

NANOPARTICLES AND THEIR APPLICATIONS IN CELL AND MOLECULAR BIOLOGY

PubMed Central

Wang, Edina C.; Wang, Andrew Z.

2013-01-01

Nanoparticles can be engineered with distinctive compositions, sizes, shapes, and surface chemistries to enable novel techniques in a wide range of biological applications. The unique properties of nanoparticles and their behavior in biological milieu also enable exciting and integrative approaches to studying fundamental biological questions. This review will provide an overview of various types of nanoparticles and concepts of targeting nanoparticles. We will also discuss the advantages and recent applications of using nanoparticles as tools for drug delivery, imaging, sensing, and for the understanding of basic biological processes. PMID:24104563

Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region.

PubMed

McEwen, Lisa M; Morin, Alexander M; Edgar, Rachel D; MacIsaac, Julia L; Jones, Meaghan J; Dow, William H; Rosero-Bixby, Luis; Kobor, Michael S; Rehkopf, David H

2017-01-01

The Nicoya Peninsula in Costa Rica has one of the highest old-age life expectancies in the world, but the underlying biological mechanisms of this longevity are not well understood. As DNA methylation is hypothesized to be a component of biological aging, we focused on this malleable epigenetic mark to determine its association with current residence in Nicoya versus elsewhere in Costa Rica. Examining a population's unique DNA methylation pattern allows us to differentiate hallmarks of longevity from individual stochastic variation. These differences may be characteristic of a combination of social, biological, and environmental contexts. In a cross-sectional subsample of the Costa Rican Longevity and Healthy Aging Study, we compared whole blood DNA methylation profiles of residents from Nicoya ( n  = 48) and non-Nicoya (other Costa Rican regions, n  = 47) using the Infinium HumanMethylation450 microarray. We observed a number of differences that may be markers of delayed aging, such as bioinformatically derived differential CD8+ T cell proportions. Additionally, both site- and region-specific analyses revealed DNA methylation patterns unique to Nicoyans. We also observed lower overall variability in DNA methylation in the Nicoyan population, another hallmark of younger biological age. Nicoyans represent an interesting group of individuals who may possess unique immune cell proportions as well as distinct differences in their epigenome, at the level of DNA methylation.

Traceability in stem cell research: from participant sample to induced pluripotent stem cell and back.

PubMed

Morrison, Michael; Moraia, Linda Briceño; Steele, Jane C

2016-01-01

This paper describes a traceability system developed for the Stem cells for Biological Assays of Novel drugs and prediCtive toxiCology consortium. The system combines records and labels that to biological material across geographical locations and scientific processes from sample donation to induced pluripotent stem cell line. The labeling system uses a unique identification number to link every aliquot of sample at every stage of the reprogramming pathway back to the original donor. Only staff at the clinical recruitment site can reconnect the unique identification number to the identifying details of a specific donor. This ensures the system meets ethical and legal requirements for protecting privacy while allowing full traceability of biological material. The system can be adapted to other projects and for use with different primary sample types.

Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

PubMed Central

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-01-01

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

PubMed

Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

2013-10-11

The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

Dynamic biophotonics: female squid exhibit sexually dimorphic tunable leucophores and iridocytes.

PubMed

DeMartini, Daniel G; Ghoshal, Amitabh; Pandolfi, Erica; Weaver, Aaron T; Baum, Mary; Morse, Daniel E

2013-10-01

Loliginid squid use tunable multilayer reflectors to modulate the optical properties of their skin for camouflage and communication. Contained inside specialized cells called iridocytes, these photonic structures have been a model for investigations into bio-inspired adaptive optics. Here, we describe two distinct sexually dimorphic tunable biophotonic features in the commercially important species Doryteuthis opalescens: bright stripes of rainbow iridescence on the mantle just beneath each fin attachment and a bright white stripe centered on the dorsal surface of the mantle between the fins. Both of these cellular features are unique to the female; positioned in the same location as the conspicuously bright white testis in the male, they are completely switchable, transitioning between transparency and high reflectivity. The sexual dimorphism, location and tunability of these features suggest that they may function in mating or reproduction. These features provide advantageous new models for investigation of adaptive biophotonics. The intensely reflective cells of the iridescent stripes provide a greater signal-to-noise ratio than the adaptive iridocytes studied thus far, while the cells constituting the white stripe are adaptive leucophores--unique biological tunable broadband scatterers containing Mie-scattering organelles activated by acetylcholine, and a unique complement of reflectin proteins.

Ultrastructural dynamics of human reproduction, from ovulation to fertilization and early embryo development.

PubMed

Familiari, Giuseppe; Heyn, Rosemarie; Relucenti, Michela; Nottola, Stefania A; Sathananthan, A Henry

2006-01-01

This study describes the updated, fine structure of human gametes, the human fertilization process, and human embryos, mainly derived from assisted reproductive technology (ART). As clearly shown, the ultrastructure of human reproduction is a peculiar multistep process, which differs in part from that of other mammalian models, having some unique features. Particular attention has been devoted to the (1) sperm ultrastructure, likely "Tygerberg (Kruger) strict morphology criteria"; (2) mature oocyte, in which the MII spindle is barrel shaped, anastral, and lacking centrioles; (3) three-dimensional microarchitecture of the zona pellucida with its unique supramolecular filamentous organization; (4) sperm-egg interactions with the peculiarity of the sperm centrosome that activates the egg and organizes the sperm aster and mitotic spindles of the embryo; and (5) presence of viable cumulus cells whose metabolic activity is closely related to egg and embryo behavior in in vitro as well as in vivo conditions, in a sort of extraovarian "microfollicular unit." Even if the ultrastructural morphodynamic features of human fertilization are well understood, our knowledge about in vivo fertilization is still very limited and the complex sequence of in vivo biological steps involved in human reproduction is only partially reproduced in current ART procedures.

Weak synchronization and large-scale collective oscillation in dense bacterial suspensions

NASA Astrophysics Data System (ADS)

Wu, Yilin

Collective oscillatory behavior is ubiquitous in nature and it plays a vital role in many biological processes. Collective oscillations in biological multicellular systems often arise from coupling mediated by diffusive chemicals, by electrochemical mechanisms, or by biomechanical interaction between cells and their physical environment. In these examples, the phase of some oscillatory intracellular degree of freedom is synchronized. Here, in contrast, we discovered a unique 'weak synchronization' mechanism that does not require long-range coupling, nor even inherent oscillation of individual cells: We found that millions of motile cells in dense bacterial suspensions can self-organize into highly robust collective oscillatory motion, while individuals move in an erratic manner. Over large spatial scales we found that the phase of the oscillations is in fact organized into a centimeter scale traveling wave. We present a model of noisy self-propelled particles with strictly local interactions that accounts faithfully for our observations. These findings expand our knowledge of biological self-organization and reveal a new type of long-range order in active matter systems. The mechanism of collective oscillation uncovered here may inspire new strategies to control the self-organization of active matter and swarming robots. This work is supported by funding from CUHK Direct research Grants (4053019, 4053079, 4053130), the Research Grants Council of HKSAR (RGC Ref. No. CUHK 409713), and from the National Natural Science Foundation of China (NSFC 21473152).

Stability improvement of immobilized lactoperoxidase using polyaniline polymer.

PubMed

Jafary, Fariba; Kashanian, Soheila; Sharieat, Ziadin Samsam; Jafary, Farzaneh; Omidfar, Kobra; Paknejad, Maliheh

2012-12-01

Enzyme engineering via immobilization techniques is perfectly compatible against the other chemical or biological approximate to improve enzyme functions and stability. In this study lactoperoxidase was immobilized onto polyaniline polymer activated with glutaraldehyde as a bifunctional agent, to improve enzyme properties. Polyaniline polymer was used due its unique physical and chemical properties to immobilize lactoperoxidase (LPO). The optimum activity of immobilized LPO was observed at pH 6 and 55 °C, which has been increased about 10 °C for the immobilized enzyme. The immobilized enzyme maintained absolutely active for 60 days whereas the native enzyme lost 80 % of its initial activity within this period of time. Moreover, the immobilized enzyme can be reused for several times without loss of activity. The kinetic parameter studies showed slight differences between free and immobilized enzymes. The K(m) and K(m.app) were calculated to be 0.6 and 0.4; also V(max) and V(max.app) were 1.3 and 0.9 respectively.

Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis

NASA Astrophysics Data System (ADS)

Huang, Jia-Lin; Jiang, Gan; Song, Qing-Xiang; Gu, Xiao; Hu, Meng; Wang, Xiao-Lin; Song, Hua-Hua; Chen, Le-Pei; Lin, Ying-Ying; Jiang, Di; Chen, Jun; Feng, Jun-Feng; Qiu, Yong-Ming; Jiang, Ji-Yao; Jiang, Xin-Guo; Chen, Hong-Zhuan; Gao, Xiao-Ling

2017-05-01

Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to `drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.

Fluctuations and symmetries in two-dimensional active gels.

PubMed

Sarkar, N; Basu, A

2011-04-01

Motivated by the unique physical properties of biological active matter, e.g., cytoskeletal dynamics in eukaryotic cells, we set up effective two-dimensional (2d) coarse-grained hydrodynamic equations for the dynamics of thin active gels with polar or nematic symmetries. We use the well-known three-dimensional (3d) descriptions (K. Kruse et al., Eur. Phys. J. E 16, 5 (2005); A. Basu et al., Eur. Phys. J. E 27, 149 (2008)) for thin active-gel samples confined between parallel plates with appropriate boundary conditions to derive the effective 2d constitutive relations between appropriate thermodynamic fluxes and generalised forces for small deviations from equilibrium. We consider three distinct cases, characterised by spatial symmetries and boundary conditions, and show how such considerations dictate the structure of the constitutive relations. We use these to study the linear instabilities, calculate the correlation functions and the diffusion constant of a small tagged particle, and elucidate their dependences on the activity or nonequilibrium drive.

Son of sevenless directly links the Robo receptor to rac activation to control axon repulsion at the midline.

PubMed

Yang, Long; Bashaw, Greg J

2006-11-22

Son of sevenless (Sos) is a dual specificity guanine nucleotide exchange factor (GEF) that regulates both Ras and Rho family GTPases and thus is uniquely poised to integrate signals that affect both gene expression and cytoskeletal reorganization. Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand. Intriguingly, the Ras and Rac-GEF activities of Sos can be uncoupled during Robo-mediated axon repulsion; Sos axon guidance function depends on its Rac-GEF activity, but not its Ras-GEF activity. These results provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules and support a model in which Robo recruits Sos to the membrane via Dock to activate Rac during midline repulsion.

2-Guanidino-quinazolines as a novel class of translation inhibitors.

PubMed

Komarova Andreyanova, E S; Osterman, I A; Pletnev, P I; Ivanenkov, Y A; Majouga, A G; Bogdanov, A A; Sergiev, P V

2017-02-01

A variety of structurally unrelated organic compounds has been reported to have antibacterial activity. Among these, certain small-molecule translation inhibitors have attracted a great deal of attention, due to their relatively high selectivity against prokaryotes, and an appropriate therapeutic index with minor "off target" effects. However, ribosomes are being considered as poorly druggable biological targets, thereby making some routine computational-based approaches to rational drug design and its development rather ineffective. Taking this into account, diversity-oriented biological screening can reasonably be considered as the most advantageous strategy. Thus, using a high-throughput screening (HTS) platform, we applied a unique biological assay for in vitro evaluation of thousands of organic molecules, especially targeted against bacterial ribosomes and translation. As a result, we have identified a series of structurally diverse small-molecule compounds that induce a reporter strain sensitive to translation and DNA biosynthesis inhibitors. In a cell free system, several molecules were found to strongly inhibit protein biosynthesis. Among them, compounds bearing a 2-guanidino-quinazoline core demonstrated the most promising antibacterial activity. With regard to the preliminary structure-activity relationship (SAR) study, we revealed that relatively small substituents at positions 4, 6 and 8 of the quinazoline ring significantly enhance the target activity whereas modification of the guanidine group leads to decrease or loss of antibacterial potency. This novel class of translation inhibitors can properly be regarded as a promising starting point for the development of novel antibacterial therapeutic or screening tools. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Marine-Derived Bioactive Peptides for Biomedical Sectors: A Review.

PubMed

Ruiz-Ruiz, Federico; Mancera-Andrade, Elena I; Iqbal, Hafiz M N

2017-01-01

Marine-based resources such as algae and other marine by-products have been recognized as rich sources of structurally diverse bioactive peptides. Evidently, their structural characteristics including unique amino acid residues are responsible for their biological activity. Several of the above-mentioned marine-origin species show multi-functional bioactivities that are useful for a new discovery and/or reinvention of biologically active ingredients, nutraceuticals and/or pharmaceuticals. Therefore, in recent years, marine-derived bioactive peptides have gained a considerable attention with high-value biomedical and/or pharmaceutical potentials. Furthermore, a wider spectrum of bioactive peptides can be produced through proteolytic-assisted hydrolysis of various marine resources under controlled physicochemical (pH and temperature of the reaction media) environment. Owing to their numerous health-related beneficial effects and therapeutic potential in the treatment and/or prevention of many diseases, such marine-derived bioactive peptides exhibit a wider spectrum of biological activities such as anti-cancerous, anti-proliferative, anti-coagulant, antibacterial, antifungal, and anti-tumor activities among many others. Based on emerging evidence of marine-derived peptide mining, the above-mentioned marine resources contain noteworthy levels of high-value protein. The present review article mainly summarizes the marine-derived bioactive peptides and emphasizing their potential applications in biomedical and/or pharmaceutical sectors of the modern world. In conclusion, recent literature has provided evidence that marine-derived bioactive peptides play a critical role in human health along with many possibilities of designing new functional nutraceuticals and/or pharmaceuticals to clarify potent mechanisms of action for a wider spectrum of diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A new neuroinformatics approach to personalized medicine in neurology: The Virtual Brain

PubMed Central

Falcon, Maria I.; Jirsa, Viktor; Solodkin, Ana

2017-01-01

Purpose of review An exciting advance in the field of neuroimaging is the acquisition and processing of very large data sets (so called ‘big data’), permitting large-scale inferences that foster a greater understanding of brain function in health and disease. Yet what we are clearly lacking are quantitative integrative tools to translate this understanding to the individual level to lay the basis for personalized medicine. Recent findings Here we address this challenge through a review on how the relatively new field of neuroinformatics modeling has the capacity to track brain network function at different levels of inquiry, from microscopic to macroscopic and from the localized to the distributed. In this context, we introduce a new and unique multiscale approach, The Virtual Brain (TVB), that effectively models individualized brain activity, linking large-scale (macroscopic) brain dynamics with biophysical parameters at the microscopic level. We also show how TVB modeling provides unique biological interpretable data in epilepsy and stroke. Summary These results establish the basis for a deliberate integration of computational biology and neuroscience into clinical approaches for elucidating cellular mechanisms of disease. In the future, this can provide the means to create a collection of disease-specific models that can be applied on the individual level to personalize therapeutic interventions. Video abstract http://links.lww.com/CONR/A41 PMID:27224088

Understanding Prebiotic Chemistry Through the Analysis of Extraterrestrial Amino Acids and Nucleobases in Meteorites

NASA Technical Reports Server (NTRS)

Burton, Aaron S.; Stern, Jennifer C.; Elsila, Jamie E.; Glavin, Daniel P.; Dworkin, Jason P.

2012-01-01

The discoveries of amino acids of extraterrestrial origin in many meteorites over the last 50 years have revolutionized the Astrobiology field. A variety of non-terrestrial amino acids similar to those found in life on Earth have been detected in meteorites. A few amino acids have even been found with chiral excesses, suggesting that meteorites could have contributed to the origin of homochirality in life on Earth. In addition to amino acids, which have been productively studied for years, sugar-like molecules, activated phosphates, and nucleobases have also been determined to be indigenous to numerous meteorites. Because these molecules are essential for life as we know it, and meteorites have been delivering them to the Earth since accretion, it is plausible that the origines) of life on Earth were aided by extrataterrestrially-synthesized molecules. Understanding the origins of life on Earth guides our search for life elsewhere, helping to answer the question of whether biology is unique to Earth. This tutorial focuses on meteoritic amino acids and nucleobases, exploring modern analytical methods and possible formation mechanisms. We will also discuss the unique window that meteorites provide into the chemistry that preceded life on Earth, a chemical record we do not have access to on Earth due to geologic recycling of rocks and the pervasiveness of biology across the planet. Finally. we will address the future of meteorite research, including asteroid sample return missions.

Enabling cell-cell communication via nanopore formation: structure, function and localization of the unique cell wall amidase AmiC2 of Nostoc punctiforme.

PubMed

Büttner, Felix M; Faulhaber, Katharina; Forchhammer, Karl; Maldener, Iris; Stehle, Thilo

2016-04-01

To orchestrate a complex life style in changing environments, the filamentous cyanobacterium Nostoc punctiforme facilitates communication between neighboring cells through septal junction complexes. This is achieved by nanopores that perforate the peptidoglycan (PGN) layer and traverse the cell septa. The N-acetylmuramoyl-l-alanine amidase AmiC2 (Npun_F1846; EC 3.5.1.28) in N. punctiforme generates arrays of such nanopores in the septal PGN, in contrast to homologous amidases that mediate daughter cell separation after cell division in unicellular bacteria. Nanopore formation is therefore a novel property of AmiC homologs. Immunofluorescence shows that native AmiC2 localizes to the maturing septum. The high-resolution crystal structure (1.12 Å) of its catalytic domain (AmiC2-cat) differs significantly from known structures of cell splitting and PGN recycling amidases. A wide and shallow binding cavity allows easy access of the substrate to the active site, which harbors an essential zinc ion. AmiC2-cat exhibits strong hydrolytic activity in vitro. A single point mutation of a conserved glutamate near the zinc ion results in total loss of activity, whereas zinc removal leads to instability of AmiC2-cat. An inhibitory α-helix, as found in the Escherichia coli AmiC(E. coli) structure, is absent. Taken together, our data provide insight into the cell-biological, biochemical and structural properties of an unusual cell wall lytic enzyme that generates nanopores for cell-cell communication in multicellular cyanobacteria. The novel structural features of the catalytic domain and the unique biological function of AmiC2 hint at mechanisms of action and regulation that are distinct from other amidases. The AmiC2-cat structure has been deposited in the Protein Data Bank under accession number 5EMI. © 2016 Federation of European Biochemical Societies.

Father-adolescent engagement in shared activities: Effects on cortisol stress response in young adulthood.

PubMed

Ibrahim, Mariam Hanna; Somers, Jennifer A; Luecken, Linda J; Fabricius, William V; Cookston, Jeffrey T

2017-06-01

Parent-child relationships can critically affect youth physiological development. Most studies have focused on the influence of maternal behaviors, with little attention to paternal influences. The current study investigated father engagement with their adolescents in household (shopping, cooking) and discretionary leisure activities as a predictor of youth cortisol response to a challenging interpersonal task in young adulthood. The sample (N = 213) was roughly divided between Mexican American (MA; n = 101) and European American (EA; n = 112) families, and included resident biological-father (n = 131) and resident stepfather families (n = 82). Salivary cortisol was collected before, immediately after, and at 20 and 40 min after an interpersonal challenge task; area under the curve (AUCg) was calculated to capture total cortisol output. Results suggested that more frequent father engagement in shared activities with adolescents (ages 11-16), but not mother engagement, predicted lower AUCg cortisol response in young adulthood (ages 19-22). The relation remained significant after adjusting for current mother and father engagement and current mental health. Further, the relation did not differ given family ethnicity, father type (step or biological), or adolescent sex. Future research should consider unique influences of fathers when investigating the effects of parent-child relationships on youth physiological development and health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

PubMed

Lee, Irene; Berdis, Anthony J

2016-01-01

Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. Copyright © 2015 Elsevier B.V. All rights reserved.

The diversity and antibiotic properties of actinobacteria associated with endemic deepwater amphipods of Lake Baikal.

PubMed

Protasov, Eugenii S; Axenov-Gribanov, Denis V; Rebets, Yuriy V; Voytsekhovskaya, Irina V; Tokovenko, Bogdan T; Shatilina, Zhanna M; Luzhetskyy, Andriy N; Timofeyev, Maxim A

2017-12-01

The emergence of pathogenic bacteria resistant to antibiotics increases the need for discovery of new effective antimicrobials. Unique habitats such as marine deposits, wetlands and caves or unexplored biological communities are promising sources for the isolation of actinobacteria, which are among the major antibiotic producers. The present study aimed at examining cultivated actinobacteria strains associated with endemic Lake Baikal deepwater amphipods and estimating their antibiotic activity. We isolated 42 actinobacterial strains from crustaceans belonging to Ommatogammarus albinus and Ommatogammarus flavus. To our knowledge, this is the first report describing the isolation and initial characterization of representatives of Micromonospora and Pseudonocardia genera from Baikal deepwater invertebrates. Also, as expected, representatives of the genus Streptomyces were the dominant group among the isolated species. Some correlations could be observed between the number of actinobacterial isolates, the depth of sampling and the source of the strains. Nevertheless, >70% of isolated strains demonstrated antifungal activity. The dereplication analysis of extract of one of the isolated strains resulted in annotation of several known compounds that can help to explain the observed biological activities. The characteristics of ecological niche and lifestyle of deepwater amphipods suggests that the observed associations between crustaceans and isolated actinobacteria are not random and might represent long-term symbiotic interactions.

Antimicrobial activities of endophytic fungi obtained from the arid zone invasive plant Opuntia dillenii and the isolation of equisetin, from endophytic Fusarium sp.

PubMed

Ratnaweera, Pamoda B; de Silva, E Dilip; Williams, David E; Andersen, Raymond J

2015-07-10

Opuntia dillenii is an invasive plant well established in the harsh South-Eastern arid zone of Sri Lanka. Evidence suggests it is likely that the endophytic fungal populations of O. dillenii assist the host in overcoming biotic and abiotic stress by producing biologically active metabolites. With this in mind there is potential to discover novel natural products with useful biological activities from this hitherto poorly investigated source. Consequently, an investigation of the antimicrobial activities of the endophytes of O. dillenii, that occupies a unique ecological niche, may well provide useful leads in the discovery of new pharmaceuticals. Endophytic fungi were isolated from the surface sterilized cladodes and flowers of O. dillenii using several nutrient media and the antimicrobial activities were evaluated against three Gram-positive and two Gram-negative bacteria and Candida albicans. The two most bioactive fungi were identified by colony morphology and DNA sequencing. The secondary metabolite of the endophyte Fusarium sp. exhibiting the best activity was isolated via bioassay guided chromatography. The chemical structure was elucidated from the ESIMS and NMR spectroscopic data obtained for the active metabolite. The minimum inhibitory concentrations (MICs) of the active compound were determined. Eight endophytic fungi were isolated from O. dillenii and all except one showed antibacterial activities against at least one of the test bacteria. All extracts were inactive against C. albicans. The most bioactive fungus was identified as Fusarium sp. and the second most active as Aspergillus niger. The structure of the major antibacterial compound of the Fusarium sp. was shown to be the tetramic acid derivative, equisetin. The MIC's for equisetin were 8 μg mL(-1) against Bacillus subtilis, 16 μg mL(-1) against Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus (MRSA). O. dillenii, harbors several endophytic fungi capable of producing antimicrobial substances with selective antibacterial properties. By producing biologically active secondary metabolites, such as equisetin isolated from the endophytic Fusarium sp., the endophytic fungal population may be assisting the host to successfully withstand stressful environmental conditions. Further investigations on the secondary metabolites produced by these endophytes may provide additional drug leads.

Live-cell imaging of cell signaling using genetically encoded fluorescent reporters.

PubMed

Ni, Qiang; Mehta, Sohum; Zhang, Jin

2018-01-01

Synergistic advances in fluorescent protein engineering and live-cell imaging techniques in recent years have fueled the concurrent development and application of genetically encoded fluorescent reporters that are tailored for tracking signaling dynamics in living systems over multiple length and time scales. These biosensors are uniquely suited for this challenging task, owing to their specificity, sensitivity, and versatility, as well as to the noninvasive and nondestructive nature of fluorescence and the power of genetic encoding. Over the past 10 years, a growing number of fluorescent reporters have been developed for tracking a wide range of biological signals in living cells and animals, including second messenger and metabolite dynamics, enzyme activation and activity, and cell cycle progression and neuronal activity. Many of these biosensors are gaining wide use and are proving to be indispensable for unraveling the complex biological functions of individual signaling molecules in their native environment, the living cell, shedding new light on the structural and molecular underpinnings of cell signaling. In this review, we highlight recent advances in protein engineering that are likely to help expand and improve the design and application of these valuable tools. We then turn our focus to specific examples of live-cell imaging using genetically encoded fluorescent reporters as an important platform for advancing our understanding of G protein-coupled receptor signaling and neuronal activity. © 2017 Federation of European Biochemical Societies.

The Bacterial Communities of Full-Scale Biologically Active, Granular Activated Carbon Filters Are Stable and Diverse and Potentially Contain Novel Ammonia-Oxidizing Microorganisms

PubMed Central

Hope Wilkinson, Katheryn; Strait, Jacqueline M.; Hozalski, Raymond M.; Sadowksy, Michael J.; Hamilton, Matthew J.

2015-01-01

The bacterial community composition of the full-scale biologically active, granular activated carbon (BAC) filters operated at the St. Paul Regional Water Services (SPRWS) was investigated using Illumina MiSeq analysis of PCR-amplified 16S rRNA gene fragments. These bacterial communities were consistently diverse (Shannon index, >4.4; richness estimates, >1,500 unique operational taxonomic units [OTUs]) throughout the duration of the 12-month study period. In addition, only modest shifts in the quantities of individual bacterial populations were observed; of the 15 most prominent OTUs, the most highly variable population (a Variovorax sp.) modulated less than 13-fold over time and less than 8-fold from filter to filter. The most prominent population in the profiles was a Nitrospira sp., representing 13 to 21% of the community. Interestingly, very few of the known ammonia-oxidizing bacteria (AOB; <0.07%) and no ammonia-oxidizing Archaea were detected in the profiles. Quantitative PCR of amoA genes, however, suggested that AOB were prominent in the bacterial communities (amoA/16S rRNA gene ratio, 1 to 10%). We conclude, therefore, that the BAC filters at the SPRWS potentially contained significant numbers of unidentified and novel ammonia-oxidizing microorganisms that possess amoA genes similar to those of previously described AOB. PMID:26209671

Neuroengineering control and regulation of behavior

NASA Astrophysics Data System (ADS)

Wróbel, A.; Radzewicz, C.; Mankiewicz, L.; Hottowy, P.; Knapska, E.; Konopka, W.; Kublik, E.; Radwańska, K.; Waleszczyk, W. J.; Wójcik, D. K.

2014-11-01

To monitor neuronal circuits involved in emotional modulation of sensory processing we proposed a plan to establish novel research techniques combining recent biological, technical and analytical discoveries. The project was granted by National Science Center and we started to build a new experimental model for studying the selected circuits of genetically marked and behaviorally activated neurons. To achieve this goal we will combine the pioneering, interdisciplinary expertise of four Polish institutions: (i) the Nencki Institute of Experimental Biology (Polish Academy of Sciences) will deliver the expertise on genetically modified mice and rats, mapping of the neuronal circuits activated by behavior, monitoring complex behaviors measured in the IntelliCage system, electrophysiological brain activity recordings by multielectrodes in behaving animals, analysis and modeling of behavioral and electrophysiological data; (ii) the AGH University of Science and Technology (Faculty of Physics and Applied Computer Sciences) will use its experience in high-throughput electronics to build multichannel systems for recording the brain activity of behaving animals; (iii) the University of Warsaw (Faculty of Physics) and (iv) the Center for Theoretical Physics (Polish Academy of Sciences) will construct optoelectronic device for remote control of opto-animals produced in the Nencki Institute based on the unique experience in laser sources, studies of light propagation and its interaction with condensed media, wireless medical robotic systems, fast readout opto-electronics with control software and micromechanics.

Connecting Biology and Organic Chemistry Introductory Laboratory Courses through a Collaborative Research Project

ERIC Educational Resources Information Center

Boltax, Ariana L.; Armanious, Stephanie; Kosinski-Collins, Melissa S.; Pontrello, Jason K.

2015-01-01

Modern research often requires collaboration of experts in fields, such as math, chemistry, biology, physics, and computer science to develop unique solutions to common problems. Traditional introductory undergraduate laboratory curricula in the sciences often do not emphasize connections possible between the various disciplines. We designed an…

Biological field stations: research legacies and sites for serendipity

Treesearch

William K. Michener; Keith L. Bildstein; Arthur McKee; Robert R. Parmenter; William W. Hargrove; Deedra McClearn; Mark Stromberg

2009-01-01

Biological field stations are distributed throughout North America, capturing much of the ecological variability present at the continental scale and encompassing many unique habitats. In addition to their role in supporting research and education, field stations offer legacies of data, specimens, and accumulated knowledge. Such legacies often provide the only...

Investigating the potential of biological control against Phytophthora ramorum

Treesearch

Timothy L. Widmer

2008-01-01

Phytophthora ramorum is a unique organism in many ways, having a broad host range and both soilborne and aerial infection stages. This makes mplementing effective control measures very complex. The use of biological control has been demonstrated against various Phytophthora spp. in general, but not specifically against P...

The Biological Basis of Learning and Individuality.

ERIC Educational Resources Information Center

Kandel, Eric R.; Hawkins, Robert D.

1992-01-01

Describes the biological basis of learning and individuality. Presents an overview of recent discoveries that suggest learning engages a simple set of rules that modify the strength of connection between neurons in the brain. The changes are cited as playing an important role in making each individual unique. (MCO)

Microbial Mats of the Tswaing Impact Crater: Results of a South African Exobiology Expedition and Implications for the Search for Biological Molecules on Mars

NASA Astrophysics Data System (ADS)

Cockell, C. S.; Brandt, D.; Hand, K.; Lee, P.

2001-03-01

We describe microbial mats from the Tswaing impact crater in South Africa. The mats provide insights into the unique biological characteristics of impact craters and can help strategies for the search for biomolecules on Mars.

Proteolytic activation of the protease-activated receptor (PAR)-2 by the glycosylphosphatidylinositol-anchored serine protease testisin.

PubMed

Driesbaugh, Kathryn H; Buzza, Marguerite S; Martin, Erik W; Conway, Gregory D; Kao, Joseph P Y; Antalis, Toni M

2015-02-06

Protease-activated receptors (PARs) are a family of seven-transmembrane, G-protein-coupled receptors that are activated by multiple serine proteases through specific N-terminal proteolytic cleavage and the unmasking of a tethered ligand. The majority of PAR-activating proteases described to date are soluble proteases that are active during injury, coagulation, and inflammation. Less investigation, however, has focused on the potential for membrane-anchored serine proteases to regulate PAR activation. Testisin is a unique trypsin-like serine protease that is tethered to the extracellular membrane of cells through a glycophosphatidylinositol (GPI) anchor. Here, we show that the N-terminal domain of PAR-2 is a substrate for testisin and that proteolytic cleavage of PAR-2 by recombinant testisin activates downstream signaling pathways, including intracellular Ca(2+) mobilization and ERK1/2 phosphorylation. When testisin and PAR-2 are co-expressed in HeLa cells, GPI-anchored testisin specifically releases the PAR-2 tethered ligand. Conversely, knockdown of endogenous testisin in NCI/ADR-Res ovarian tumor cells reduces PAR-2 N-terminal proteolytic cleavage. The cleavage of PAR-2 by testisin induces activation of the intracellular serum-response element and NFκB signaling pathways and the induction of IL-8 and IL-6 cytokine gene expression. Furthermore, the activation of PAR-2 by testisin results in the loss and internalization of PAR-2 from the cell surface. This study reveals a new biological substrate for testisin and is the first demonstration of the activation of a PAR by a serine protease GPI-linked to the cell surface. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Biomedical and Catalytic Opportunities of Virus-Like Particles in Nanotechnology.

PubMed

Schwarz, B; Uchida, M; Douglas, T

2017-01-01

Within biology, molecules are arranged in hierarchical structures that coordinate and control the many processes that allow for complex organisms to exist. Proteins and other functional macromolecules are often studied outside their natural nanostructural context because it remains difficult to create controlled arrangements of proteins at this size scale. Viruses are elegantly simple nanosystems that exist at the interface of living organisms and nonliving biological machines. Studied and viewed primarily as pathogens to be combatted, viruses have emerged as models of structural efficiency at the nanoscale and have spurred the development of biomimetic nanoparticle systems. Virus-like particles (VLPs) are noninfectious protein cages derived from viruses or other cage-forming systems. VLPs provide incredibly regular scaffolds for building at the nanoscale. Composed of self-assembling protein subunits, VLPs provide both a model for studying materials' assembly at the nanoscale and useful building blocks for materials design. The robustness and degree of understanding of many VLP structures allow for the ready use of these systems as versatile nanoparticle platforms for the conjugation of active molecules or as scaffolds for the structural organization of chemical processes. Lastly the prevalence of viruses in all domains of life has led to unique activities of VLPs in biological systems most notably the immune system. Here we discuss recent efforts to apply VLPs in a wide variety of applications with the aim of highlighting how the common structural elements of VLPs have led to their emergence as paradigms for the understanding and design of biological nanomaterials. © 2017 Elsevier Inc. All rights reserved.

Direct Acylation of C(sp(3))-H Bonds Enabled by Nickel and Photoredox Catalysis.

PubMed

Joe, Candice L; Doyle, Abigail G

2016-03-14

Using nickel and photoredox catalysis, the direct functionalization of C(sp(3))-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of α-amino ketones at room temperature and is amenable to late-stage coupling of complex and biologically relevant groups. C(sp(3))-H activation occurs by photoredox-mediated oxidation to generate α-amino radicals which are intercepted by nickel in catalytic C(sp(3))-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross-coupling while avoiding limitations commonly associated with transition-metal-mediated C(sp(3))-H activation, including requirements for chelating directing groups and high reaction temperatures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Emerging Therapeutics Targeting mRNA Translation

PubMed Central

Malina, Abba; Mills, John R.; Pelletier, Jerry

2012-01-01

A defining feature of many cancers is deregulated translational control. Typically, this occurs at the level of recruitment of the 40S ribosomes to the 5′-cap of cellular messenger RNAs (mRNAs), the rate-limiting step of protein synthesis, which is controlled by the heterotrimeric eukaryotic initiation complex eIF4F. Thus, eIF4F in particular, and translation initiation in general, represent an exploitable vulnerability and unique opportunity for therapeutic intervention in many transformed cells. In this article, we discuss the development, mode of action and biological activity of a number of small-molecule inhibitors that interrupt PI3K/mTOR signaling control of eIF4F assembly, as well as compounds that more directly block eIF4F activity. PMID:22474009

Peatlands as a unique climatic hotspots

NASA Astrophysics Data System (ADS)

Slowinska, S.; Marcisz, K.; Slowinski, M. M.; Blazejczyk, K.; Lamentowicz, M.

2017-12-01

Peatlands are unique environments, often acting as microrefugia of various taxa. High groundwater table, organic soils, specific vegetation and topography are important determinants of their local climatic conditions. However, relations between those determinants are not stable. For example, seasonal changes in weather patterns, hydrological dynamics, and local vegetation may alter microclimate. Additionally, long-term changes are important factor, as for example overgrowing due to significant change of microclimate conditions, what in turn changes geochemical and biological processes in the peat layer. We have been investigating interactions between abiotic and biotic factors of a small Sphagnum mire (ca. 6.0 ha) for over ten years now. The mire is located in Poland in transitional temperate climate and is the only place in polish lowlands where glacial relict Betula nana occurs. Identification of local climate of the mire, its microclimatic differentiation and its influence on surroundings were objectives of the study. We recorded water level fluctuations, photosynthetically active radiation (PAR), air temperature and humidity, and peat temperature at five monitoring plots at the mire and observed significant differences between them. We also investigated Sphagnum mosses growth and testate amoeba diversity and community structure to understand biological response of those differences. We observed that local climate of the mire was significantly different from open area reference place, it was much colder especially during nights. The average minimal temperature at the height 30 cm for growing seasons 2010-2012 was 3.7oC lower there and ground frosts occurred even in the summer. The climate of the mire affected the forest directly adjacent to it, and depending on weather conditions the strength and the distance of this interaction was different. Our results show that micro-environmental changes affects on biological processes and should be taken into consideration in palaeoecological investigations.

Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

PubMed

Britton, David; Zen, Yoh; Quaglia, Alberto; Selzer, Stefan; Mitra, Vikram; Löβner, Christopher; Jung, Stephan; Böhm, Gitte; Schmid, Peter; Prefot, Petra; Hoehle, Claudia; Koncarevic, Sasa; Gee, Julia; Nicholson, Robert; Ward, Malcolm; Castellano, Leandro; Stebbing, Justin; Zucht, Hans Dieter; Sarker, Debashis; Heaton, Nigel; Pike, Ian

2014-01-01

LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset. Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

The Unique Morgue Ubiquitination Protein Is Conserved in a Diverse but Restricted Set of Invertebrates

PubMed Central

Zhou, Ying; Carpenter, Zachary W.; Brennan, Gregory

2009-01-01

Drosophila Morgue is a unique ubiquitination protein that facilitates programmed cell death and associates with DIAP1, a critical cell death inhibitor with E3 ubiquitin ligase activity. Morgue possesses a unique combination of functional domains typically associated with distinct types of ubiquitination enzymes. This includes an F box characteristic of the substrate-binding subunit in Skp, Cullin, and F box (SCF)-type ubiquitin E3 ligase complexes and a variant ubiquitin E2 conjugase domain where the active site cysteine is replaced by a glycine. Morgue also contains a single C4-type zinc finger motif. This architecture suggests potentially novel ubiquitination activities for Morgue. In this study, we address the evolutionary origins of this distinctive protein utilizing a combination of bioinformatics and molecular biology approaches. We find that Morgue exhibits widespread but restricted phylogenetic distribution among metazoans. Morgue proteins were identified in a wide range of Protostome phyla, including Arthropoda, Annelida, Mollusca, Nematoda, and Platyhelminthes. However, with one potential exception, Morgue was not detected in Deuterostomes, including Chordates, Hemichordates, or Echinoderms. Morgue was also not found in Ctenophora, Cnidaria, Placozoa, or Porifera. Characterization of Morgue sequences within specific animal lineages suggests that gene deletion or acquisition has occurred during divergence of nematodes and that at least one arachnid expresses an atypical form of Morgue consisting only of the variant E2 conjugase domain. Analysis of the organization of several morgue genes suggests that exon-shuffling events have contributed to the evolution of the Morgue protein. These results suggest that Morgue mediates conserved and distinctive ubiquitination functions in specific cell death pathways. PMID:19602541

Tie2 and Eph Receptor Tyrosine Kinase Activation and Signaling

PubMed Central

Barton, William A.; Dalton, Annamarie C.; Seegar, Tom C.M.; Himanen, Juha P.

2014-01-01

The Eph and Tie cell surface receptors mediate a variety of signaling events during development and in the adult organism. As other receptor tyrosine kinases, they are activated on binding of extracellular ligands and their catalytic activity is tightly regulated on multiple levels. The Eph and Tie receptors display some unique characteristics, including the requirement of ligand-induced receptor clustering for efficient signaling. Interestingly, both Ephs and Ties can mediate different, even opposite, biological effects depending on the specific ligand eliciting the response and on the cellular context. Here we discuss the structural features of these receptors, their interactions with various ligands, as well as functional implications for downstream signaling initiation. The Eph/ephrin structures are already well reviewed and we only provide a brief overview on the initial binding events. We go into more detail discussing the Tie-angiopoietin structures and recognition. PMID:24478383

Does iron inhibit cryptoendolithic microbial communities?

NASA Technical Reports Server (NTRS)

Johnston, C. G.; Vestal, J. R.; Friedmann, E. I. (Principal Investigator)

1988-01-01

Photosynthetic activity of three cryptoendolithic microbial communities was studied under controlled conditions in the laboratory. In two of these communities, the dominant organisms were lichens, collected from Linnaeus Terrace and from Battleship Promontory. The third community, dominated by cyanobacteria, was collected from Battleship Promontory. Both sites are in the ice-free valleys of southern Victoria Land. Previous efforts have shown how physical conditions can influence metabolic activity in endolithic communities (Kappen and Friedmann 1983; Kappen, Friedmann, and Garty 1981; Vestal, Federle, and Friedmann 1984). Biological activity can also be strongly influenced by the chemical environment. Inorganic nutrients such as nitrate, ammonia, and phosphate are often limiting factors, so their effects on photosynthetic carbon-14 bicarbonate incorporation were investigated. Iron and manganese are two metals present in Linnaeus Terrace and Battleship Promontory sandstones, and their effects on photosynthesis were also studied. The results may add to our understanding of biogeochemical interactions within this unique microbial community.

Cytotoxicity of Crude Lectins from Red Macroalgae from the Southern Coast of Java Island, Gunung Kidul Regency, Yogyakarta, Indonesia

NASA Astrophysics Data System (ADS)

Anam, C.; Chasanah, E.; Perdhana, B. P.; Fajarningsih, ND; Yusro, N. F.; Sari, A. M.; Nursiwi, A.; Praseptiangga, D.; Yunus, A.

2017-04-01

Lectins or carbohydrate-binding proteins, are widely distributed in nature, including in marine algae. It may have been considered that binding specificity of lectins to some carbohydrates provokes to produce many unique biological activities, including cell agglutination, mitogenic activity, and antitumor activity. The aim of this study was to determine the cytotoxicity of crude lectins from red macroalgae collected from the southern coast of Java Island, Gunung Kidul Regency, Yogyakarta against MCF-7 and HeLa cancer cells. In vitro MTT assay was used in this study. The results showed that less than 50% of MCF-7 and HeLa cancer cells growth were inhibited by the crude lectins from five species of red macro algae used in this study. The highest inhibition ability shown in the red alga A. nana was able to kill 47.68% of HeLa cervical cancer cells.

Macroenvironmental regulation of hair cycling and collective regenerative behavior.

PubMed

Plikus, Maksim V; Chuong, Cheng-Ming

2014-01-01

The hair follicle (HF) regeneration paradigm provides a unique opportunity for studying the collective behavior of stem cells in living animals. Activation of HF stem cells depends on the core inhibitory BMP and activating WNT signals operating within the HF microenvironment. Additionally, HFs receive multilayered signaling inputs from the extrafollicular macroenvironment, which includes dermis, adipocytes, neighboring HFs, hormones, and external stimuli. These activators/inhibitors are integrated across multiple stem-cell niches to produce dynamic hair growth patterns. Because of their pigmentation, these patterns can be easily studied on live shaved animals. Comparing to autonomous regeneration of one HF, populations of HFs display coupled decision making, allowing for more robust and adaptable regenerative behavior to occur collectively. The generic cellular automata model used to simulate coordinated HF cycling here can be extended to study population-level behavior of other complex biological systems made of cycling elements.

Macroenvironmental Regulation of Hair Cycling and Collective Regenerative Behavior

PubMed Central

Plikus, Maksim V.; Chuong, Cheng-Ming

2014-01-01

The hair follicle (HF) regeneration paradigm provides a unique opportunity for studying the collective behavior of stem cells in living animals. Activation of HF stem cells depends on the core inhibitory BMP and activating WNT signals operating within the HF microenvironment. Additionally, HFs receive multilayered signaling inputs from the extrafollicular macroenvironment, which includes dermis, adipocytes, neighboring HFs, hormones, and external stimuli. These activators/inhibitors are integrated across multiple stem-cell niches to produce dynamic hair growth patterns. Because of their pigmentation, these patterns can be easily studied on live shaved animals. Comparing to autonomous regeneration of one HF, populations of HFs display coupled decision making, allowing for more robust and adaptable regenerative behavior to occur collectively. The generic cellular automata model used to simulate coordinated HF cycling here can be extended to study population-level behavior of other complex biological systems made of cycling elements. PMID:24384813

Archetypal tryptophan-rich antimicrobial peptides: properties and applications.

PubMed

Shagaghi, Nadin; Palombo, Enzo A; Clayton, Andrew H A; Bhave, Mrinal

2016-02-01

Drug-resistant microorganisms ('superbugs') present a serious challenge to the success of antimicrobial treatments. Subsequently, there is a crucial need for novel bio-control agents. Many antimicrobial peptides (AMPs) show a broad-spectrum activity against bacteria, fungi or viruses and are strong candidates to complement or substitute current antimicrobial agents. Some AMPs are also effective against protozoa or cancer cells. The tryptophan (Trp)-rich peptides (TRPs) are a subset of AMPs that display potent antimicrobial activity, credited to the unique biochemical properties of tryptophan that allow it to insert into biological membranes. Further, many Trp-rich AMPs cross bacterial membranes without compromising their integrity and act intracellularly, suggesting interactions with nucleic acids and enzymes. In this work, we overview some archetypal TRPs derived from natural sources, i.e., indolicidin, tritrpticin and lactoferricin, summarising their biochemical properties, structures, antimicrobial activities, mechanistic studies and potential applications.

Kinesins and Myosins: Molecular Motors that Coordinate Cellular Functions in Plants.

PubMed

Nebenführ, Andreas; Dixit, Ram

2018-04-29

Kinesins and myosins are motor proteins that can move actively along microtubules and actin filaments, respectively. Plants have evolved a unique set of motors that function as regulators and organizers of the cytoskeleton and as drivers of long-distance transport of various cellular components. Recent progress has established the full complement of motors encoded in plant genomes and has revealed valuable insights into the cellular functions of many kinesin and myosin isoforms. Interestingly, several of the motors were found to functionally connect the two cytoskeletal systems and thereby to coordinate their activities. In this review, we discuss the available genetic, cell biological, and biochemical data for each of the plant kinesin and myosin families from the context of their subcellular mechanism of action as well as their physiological function in the whole plant. We particularly emphasize work that illustrates mechanisms by which kinesins and myosins coordinate the activities of the cytoskeletal system.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

PubMed Central

Uzair, Bushra; Tabassum, Sobia; Rasheed, Madiha; Rehman, Saima Firdous

2012-01-01

The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria. PMID:22545008

Data processing, multi-omic pathway mapping, and metabolite activity analysis using XCMS Online

PubMed Central

Forsberg, Erica M; Huan, Tao; Rinehart, Duane; Benton, H Paul; Warth, Benedikt; Hilmers, Brian; Siuzdak, Gary

2018-01-01

Systems biology is the study of complex living organisms, and as such, analysis on a systems-wide scale involves the collection of information-dense data sets that are representative of an entire phenotype. To uncover dynamic biological mechanisms, bioinformatics tools have become essential to facilitating data interpretation in large-scale analyses. Global metabolomics is one such method for performing systems biology, as metabolites represent the downstream functional products of ongoing biological processes. We have developed XCMS Online, a platform that enables online metabolomics data processing and interpretation. A systems biology workflow recently implemented within XCMS Online enables rapid metabolic pathway mapping using raw metabolomics data for investigating dysregulated metabolic processes. In addition, this platform supports integration of multi-omic (such as genomic and proteomic) data to garner further systems-wide mechanistic insight. Here, we provide an in-depth procedure showing how to effectively navigate and use the systems biology workflow within XCMS Online without a priori knowledge of the platform, including uploading liquid chromatography (LCLC)–mass spectrometry (MS) data from metabolite-extracted biological samples, defining the job parameters to identify features, correcting for retention time deviations, conducting statistical analysis of features between sample classes and performing predictive metabolic pathway analysis. Additional multi-omics data can be uploaded and overlaid with previously identified pathways to enhance systems-wide analysis of the observed dysregulations. We also describe unique visualization tools to assist in elucidation of statistically significant dysregulated metabolic pathways. Parameter input takes 5–10 min, depending on user experience; data processing typically takes 1–3 h, and data analysis takes ~30 min. PMID:29494574

Ligand-Specific Transcriptional Mechanisms Underlie Aryl Hydrocarbon Receptor-Mediated Developmental Toxicity of Oxygenated PAHs

PubMed Central

Goodale, B. C.; La Du, J.; Tilton, S. C.; Sullivan, C. M.; Bisson, W. H.; Waters, K. M.; Tanguay, R. L.

2015-01-01

Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds. PMID:26141390

Human milk proteins: key components for the biological activity of human milk.

PubMed

Lönnerdal, Bo

2004-01-01

Human milk contains a wide array of proteins that provide biologic activities ranging from antimicrobial effects to immunostimulatory functions. Proteins like lactoferrin, secretory IgA, kappa-casein, lactoperoxidase, haptocorrin, lactadherin and peptides formed from human milk proteins during digestion can inhibit the growth of pathogenic bacteria and viruses and therefore protect against infection. At the same time, proteins like lactoferrin, bile-salt stimulated lipase, haptocorrin, kappa-casein, and folate-binding protein can facilitate the absorption of nutrients in the neonatal gut. However, the proteins in human milk themselves also provide adequate amounts of essential amino acids to the growing infant. This suggests a highly adapted digestive system, which allows the survival of some proteins and peptides in the upper gastrointestinal tract, while still allowing amino acid utilization from these proteins further down in the gut. It is now possible to produce recombinant human milk proteins in transgenic plants and animals, which makes it possible to further study the bioactivity of these proteins. Provided these proteins can be produced in large scale at low cost, that they show biologic activity and pose no safety concerns, it may be possible to add some human milk proteins to infant diets, such as formula and complementary foods. Human milk proteins produced in rice or potatoes, for example, could be added without much purification, because these staples commonly are used in weaning foods. Thus, some qualities provided by human milk may be included into other diets, although it is highly unlikely that all unique components of human milk can be copied this way.

Mitochondrial Flash: Integrative Reactive Oxygen Species and pH Signals in Cell and Organelle Biology

PubMed Central

Gong, Guohua; Wang, Xianhua; Wei-LaPierre, Lan; Cheng, Heping; Dirksen, Robert

2016-01-01

Abstract Significance: Recent breakthroughs in mitochondrial research have advanced, reshaped, and revolutionized our view of the role of mitochondria in health and disease. These discoveries include the development of novel tools to probe mitochondrial biology, the molecular identification of mitochondrial functional proteins, and the emergence of new concepts and mechanisms in mitochondrial function regulation. The discovery of “mitochondrial flash” activity has provided unique insights not only into real-time visualization of individual mitochondrial redox and pH dynamics in live cells but has also advanced understanding of the excitability, autonomy, and integration of mitochondrial function in vivo. Recent Advances: The mitochondrial flash is a transient and stochastic event confined within an individual mitochondrion and is observed in a wide range of organisms from plants to Caenorhabditis elegans to mammals. As flash events involve multiple transient concurrent changes within the mitochondrion (e.g., superoxide, pH, and membrane potential), a number of different mitochondrial targeted fluorescent indicators can detect flash activity. Accumulating evidence indicates that flash events reflect integrated snapshots of an intermittent mitochondrial process arising from mitochondrial respiration chain activity associated with the transient opening of the mitochondrial permeability transition pore. Critical Issues: We review the history of flash discovery, summarize current understanding of flash biology, highlight controversies regarding the relative roles of superoxide and pH signals during a flash event, and bring forth the integration of both signals in flash genesis. Future Directions: Investigations using flash as a biomarker and establishing its role in cell signaling pathway will move the field forward. Antioxid. Redox Signal. 25, 534–549. PMID:27245241

Enzyme-regulated the changes of pH values for assembling a colorimetric and multistage interconnection logic network with multiple readouts.

PubMed

Huang, Yanyan; Ran, Xiang; Lin, Youhui; Ren, Jinsong; Qu, Xiaogang

2015-04-22

Based on enzymatic reactions-triggered changes of pH values and biocomputing, a novel and multistage interconnection biological network with multiple easy-detectable signal outputs has been developed. Compared with traditional chemical computing, the enzyme-based biological system could overcome the interference between reactions or the incompatibility of individual computing gates and offer a unique opportunity to assemble multicomponent/multifunctional logic circuitries. Our system included four enzyme inputs: β-galactosidase (β-gal), glucose oxidase (GOx), esterase (Est) and urease (Ur). With the assistance of two signal transducers (gold nanoparticles and acid-base indicators) or pH meter, the outputs of the biological network could be conveniently read by the naked eyes. In contrast to current methods, the approach present here could realize cost-effective, label-free and colorimetric logic operations without complicated instrument. By designing a series of Boolean logic operations, we could logically make judgment of the compositions of the samples on the basis of visual output signals. Our work offered a promising paradigm for future biological computing technology and might be highly useful in future intelligent diagnostics, prodrug activation, smart drug delivery, process control, and electronic applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Tumor-specific delivery of biologics by a novel T-cell line HOZOT

PubMed Central

Onishi, Teppei; Tazawa, Hiroshi; Hashimoto, Yuuri; Takeuchi, Makoto; Otani, Takeshi; Nakamura, Shuji; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kishimoto, Hiroyuki; Umeda, Yuzo; Shirakawa, Yasuhiro; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi

2016-01-01

“Cell-in-cell” denotes an invasive phenotype in which one cell actively internalizes in another. The novel human T-cell line HOZOT, established from human umbilical cord blood, was shown to penetrate a variety of human cancer cells but not normal cells. Oncolytic viruses are emerging as biological therapies for human cancers; however, efficient viral delivery is limited by a lack of tumor-specific homing and presence of pre-existing or therapy-induced neutralizing antibodies. Here, we report a new, intriguing approach using HOZOT cells to transmit biologics such as oncolytic viruses into human cancer cells by cell-in-cell invasion. HOZOT cells were successfully loaded via human CD46 antigen with an attenuated adenovirus containing the fiber protein of adenovirus serotype 35 (OBP-401/F35), in which the telomerase promoter regulates viral replication. OBP-401/F35–loaded HOZOT cells were efficiently internalized into human cancer cells and exhibited tumor-specific killing by release of viruses, even in the presence of anti-viral neutralizing antibodies. Moreover, intraperitoneal administration of HOZOT cells loaded with OBP-401/F35 significantly suppressed peritoneally disseminated tumor growth in mice. This unique cell-in-cell property provides a platform for selective delivery of biologics into human cancer cells, which has important implications for the treatment of human cancers. PMID:27901098

Ice nucleation by cellulose and its potential impact on clouds and climate

NASA Astrophysics Data System (ADS)

Hiranuma, Naruki; Möhler, Ottmar; Yamashita, Katsuya; Tajiri, Takuya; Saito, Atsushi; Kiselev, Alexei; Hoose, Corinna; Murakami, Masataka

2014-05-01

Biological aerosol particles have recently been accentuated by their efficient ice nucleating activity as well as potential impact on clouds and global climate. Despite their potential importance, little is known about the abundance of biological particles in the atmosphere and their role compared to non-biological material and, consequently, their potential role in the cloud-hydrology and climate system is also poorly constrained. However, field observations show that the concentration of airborne cellulose, which is one of the most important derivatives of glucose and atmospherically relevant biopolymers, is consistently prevalent (>10 ng per cubic meter) throughout the whole year even at remote- and elevated locations. Here we use a novel cloud simulation chamber in Tsukuba, Japan to demonstrate that airborne cellulose of biological origin can act as efficient ice nucleating particles in super-cooled clouds of the lower and middle troposphere. In specific, we measured the surface-based ice nucleation activity of microcrystalline cellulose particles immersed in cloud droplets, which may add crucial importance to further quantify the role of biological particles as ice nuclei in the troposphere. Our results suggest that the concentration of ice nucleating cellulose to become significant (>0.1 per liter) below about -17 °C and nearly comparable to other known ice nucleating clay mineral particles (e.g., illite rich clay mineral - INUIT comparisons are also presented). An important and unique characteristic of microcrystalline cellulose compared to other particles of biological origin is its high molecular packing density, enhancing resistance to hydrolysis degradation. More in-depth microphysical understandings as well as quantitative observations of ice nucleating cellulose particles in the atmosphere are necessary to allow better estimates of their effects on clouds and the global climate. Acknowledgement: We acknowledge support by German Research Society (DfG) and Ice Nucleation research UnIT (FOR 1525 INUIT).

A promising diagnostic method: Terahertz pulsed imaging and spectroscopy

PubMed Central

Sun, Yiwen; Sy, Ming Yiu; Wang, Yi-Xiang J; Ahuja, Anil T; Zhang, Yuan-Ting; Pickwell-MacPherson, Emma

2011-01-01

The terahertz band lies between the microwave and infrared regions of the electromagnetic spectrum. This radiation has very low photon energy and thus it does not pose any ionization hazard for biological tissues. It is strongly attenuated by water and very sensitive to water content. Unique absorption spectra due to intermolecular vibrations in this region have been found in different biological materials. These unique features make terahertz imaging very attractive for medical applications in order to provide complimentary information to existing imaging techniques. There has been an increasing interest in terahertz imaging and spectroscopy of biologically related applications within the last few years and more and more terahertz spectra are being reported. This paper introduces terahertz technology and provides a short review of recent advances in terahertz imaging and spectroscopy techniques, and a number of applications such as molecular spectroscopy, tissue characterization and skin imaging are discussed. PMID:21512652

Biosimilars: Considerations for Oncology Nurses
.

PubMed

Vizgirda, Vida; Jacobs, Ira

2017-04-01

Biosimilars are developed to be highly similar to and treat the same conditions as licensed biologics. As they are approved and their use becomes more widespread, oncology nurses should be aware of their development and unique considerations. This article reviews properties of biosimilars; their regulation and approval process; the ways in which their quality, safety, and efficacy are evaluated; their postmarketing safety monitoring; and their significance to oncology nurses and oncology nursing.
. A search of PubMed and regulatory agency websites was conducted for references related to the development and use of biosimilars in oncology. 
. Because biologics are large, structurally complex molecules, biosimilars cannot be considered generic equivalents to licensed biologic products. Consequently, regulatory approval for biosimilars is different from approval for small-molecule generics. Oncology nurses are in a unique position to educate themselves, other clinicians, and patients and their families about biosimilars to ensure accurate understanding, as well as optimal and safe use, of biosimilars.

Radiation biology of HZE particles

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.

1990-01-01

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets which may be related to charge, velocity, or rate of energy loss. There are many consequences of this feature to biological endpoints when compared to effects of ionizing photons. Dose vs response and dose rate kinetics are modified, DNA and cellular repair systems are altered in their abilities to cope with damage and, the qualitative features of damage are unique for different ions. These features must be incorporated into any risk assessment system for radiation health management. HZE induced mutation, cell inactivation and altered organogenesis will be discussed emphasizing studies with the nematode Caenorhabditis elegans and cultured cells. Observations from radiobiology experiments in space will also be reviewed along with plans for future space-based studies.

Ligand-Binding Affinity at the Insulin Receptor Isoform-A and Subsequent IR-A Tyrosine Phosphorylation Kinetics are Important Determinants of Mitogenic Biological Outcomes

PubMed Central

Rajapaksha, Harinda; Forbes, Briony E.

2015-01-01

The insulin receptor (IR) is a tyrosine kinase receptor that can mediate both metabolic and mitogenic biological actions. The IR isoform-A (IR-A) arises from alternative splicing of exon 11 and has different ligand binding and signaling properties compared to the IR isoform-B. The IR-A not only binds insulin but also insulin-like growth factor-II (IGF-II) with high affinity. IGF-II acting through the IR-A promotes cancer cell proliferation, survival, and migration by activating some unique signaling molecules compared to those activated by insulin. This observation led us to investigate whether the different IR-A signaling outcomes in response to IGF-II and insulin could be attributed to phosphorylation of a different subset of IR-A tyrosine residues or to the phosphorylation kinetics. We correlated IR-A phosphorylation to activation of molecules involved in mitogenic and metabolic signaling (MAPK and Akt) and receptor internalization rates (related to mitogenic signaling). We also extended this study to incorporate two ligands that are known to promote predominantly mitogenic [(His4, Tyr15, Thr49, Ile51) IGF-I, qIGF-I] or metabolic (S597 peptide) biological actions, to see if common mechanisms can be used to define mitogenic or metabolic signaling through the IR-A. The threefold lower mitogenic action of IGF-II compared to insulin was associated with a decreased potency in activation of Y960, Y1146, Y1150, Y1151, Y1316, and Y1322, in MAPK phosphorylation and in IR-A internalization. With the poorly mitogenic S597 peptide, it was a decreased rate of tyrosine phosphorylation rather than potency that was associated with a low mitogenic potential. We conclude that both decreased affinity of IR-A binding and kinetics of IR-A phosphorylation can independently lead to a lower mitogenic activity. None of the studied parameters could account for the lower metabolic activity of qIGF-I. PMID:26217307

Neural processing of intentional biological motion in unaffected siblings of children with autism spectrum disorder: an fMRI study.

PubMed

Ahmed, Alex A; Vander Wyk, Brent C

2013-12-01

Despite often showing behaviorally typical levels of social cognitive ability, unaffected siblings of children with autism spectrum disorder have been found to show similar functional and morphological deficits within brain regions associated with social processing. They have also been reported to show increased activation to biological motion in these same regions, such as the posterior superior temporal sulcus (pSTS), relative to both children with autism and control children. It has been suggested that this increased activation may represent a compensatory reorganization of these regions as a result of the highly heritable genetic influence of autism. However, the response patterns of unaffected siblings in the domain of action perception are unstudied, and the phenomenon of compensatory activation has not yet been replicated. The present study used functional magnetic resonance imaging to determine the neural responses to intentional biological actions in 22 siblings of children with autism and 22 matched controls. The presented actions were either congruent or incongruent with the actor's emotional cue. Prior studies reported that typically developing children and adults, but not children with autism, show increased activation to incongruent actions (relative to congruent), within the pSTS and dorsolateral prefrontal cortex. We report that unaffected siblings did not show a compensatory response, or a preference for incongruent over congruent trials, in any brain region. Moreover, interaction analyses revealed a sub-region of the pSTS in which control children showed an incongruency preference to a significantly greater degree than siblings, which suggests a localized deficit in siblings. A sample of children with autism also did not show differential activation in the pSTS, providing further evidence that it is an area of selective disruption in children with autism and siblings. While reduced activation to both conditions was unique to the autism sample, lack of differentiation to incongruent and congruent intentional actions was common to both children with ASD and unaffected siblings. Copyright © 2013 Elsevier Inc. All rights reserved.

Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis.

PubMed

Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M

2009-06-29

One of the challenges in the analysis of microarray data is to integrate and compare the selected (e.g., differential) gene lists from multiple experiments for common or unique underlying biological themes. A common way to approach this problem is to extract common genes from these gene lists and then subject these genes to enrichment analysis to reveal the underlying biology. However, the capacity of this approach is largely restricted by the limited number of common genes shared by datasets from multiple experiments, which could be caused by the complexity of the biological system itself. We now introduce a new Pathway Pattern Extraction Pipeline (PPEP), which extends the existing WPS application by providing a new pathway-level comparative analysis scheme. To facilitate comparing and correlating results from different studies and sources, PPEP contains new interfaces that allow evaluation of the pathway-level enrichment patterns across multiple gene lists. As an exploratory tool, this analysis pipeline may help reveal the underlying biological themes at both the pathway and gene levels. The analysis scheme provided by PPEP begins with multiple gene lists, which may be derived from different studies in terms of the biological contexts, applied technologies, or methodologies. These lists are then subjected to pathway-level comparative analysis for extraction of pathway-level patterns. This analysis pipeline helps to explore the commonality or uniqueness of these lists at the level of pathways or biological processes from different but relevant biological systems using a combination of statistical enrichment measurements, pathway-level pattern extraction, and graphical display of the relationships of genes and their associated pathways as Gene-Term Association Networks (GTANs) within the WPS platform. As a proof of concept, we have used the new method to analyze many datasets from our collaborators as well as some public microarray datasets. This tool provides a new pathway-level analysis scheme for integrative and comparative analysis of data derived from different but relevant systems. The tool is freely available as a Pathway Pattern Extraction Pipeline implemented in our existing software package WPS, which can be obtained at http://www.abcc.ncifcrf.gov/wps/wps_index.php.

NASA Space Biology Research Associate Program for the 21st Century

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

2000-01-01

The Space Biology Research Associate Program for the 21st Century provided a unique opportunity to train individuals to conduct biological research in hypo- and hyper-gravity, and to conduct ground-based research. This grant was developed to maximize the potential for Space Biology as an emerging discipline and to train a cadre of space biologists. The field of gravitational and space biology is rapidly growing at the future of the field is reflected in the quality and education of its personnel. Our chief objective was to train and develop these scientists rapidly and in a cost effective model.

Investigation of the Role of Sialomucin Complex (SCMC)/Muc4, a Unique Intramembranous HER-2/ErbB-2 Ligand, as a Suppressor of Apoptosis

DTIC Science & Technology

2005-04-01

Complex (SCMC)/ Muc4 , a Unique Intramembranous HER-2/ErbB-2 Ligand, as a Suppressor of Apoptosis PRINCIPAL INVESTIGATOR: George Theodore...1 Apr 2002 – 31 Mar 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Investigation of the Role of Sialomucin Complex (SCMC)/ Muc4 , a Unique...Seminar and Journal Club course in the Department of Cell Biology and Anatomy RESEARCH ACCOMPLISHMENTS Introduction Muc4 /sialomucin complex (SMC) is

CFP-10 from Mycobacterium tuberculosis Selectively Activates Human Neutrophils through a Pertussis Toxin-Sensitive Chemotactic Receptor

PubMed Central

Björnsdottir, Halla; Winther, Malene; Christenson, Karin; Oprea, Tudor; Karlsson, Anna; Forsman, Huamei; Dahlgren, Claes; Bylund, Johan

2014-01-01

Upon infection with Mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. Through a type VII secretion system, M. tuberculosis releases a heterodimeric protein complex, containing a 6-kDa early secreted antigenic target (ESAT-6) and a 10-kDa culture filtrate protein (CFP-10), that is essential for virulence. Whereas the ESAT-6 component possesses multiple virulence-related activities, no direct biological activity of CFP-10 has been shown, and CFP-10 has been described as a chaperone protein for ESAT-6. We here show that the ESAT-6:CFP-10 complex induces a transient release of Ca2+ from intracellular stores in human neutrophils. Surprisingly, CFP-10 rather than ESAT-6 was responsible for triggering the Ca2+ response, in a pertussis toxin-sensitive manner, suggesting the involvement of a G-protein-coupled receptor. In line with this, the response was accompanied by neutrophil chemotaxis and activation of the superoxide-producing NADPH-oxidase. Neutrophils were unique among leukocytes in responding to CFP-10, as monocytes and lymphocytes failed to produce a Ca2+ signal upon stimulation with the M. tuberculosis protein. Hence, CFP-10 may contribute specifically to neutrophil recruitment and activation during M. tuberculosis infection, representing a novel biological role for CFP-10 in the ESAT-6:CFP-10 complex, beyond the previously described chaperone function. PMID:25332123

Advanced nanocarriers based on heparin and its derivatives for cancer management.

PubMed

Yang, Xiaoye; Du, Hongliang; Liu, Jiyong; Zhai, Guangxi

2015-02-09

To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin-drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.

NASA Johnson Space Center Usability Testing and Analysis Facility (UTAF) Overview

NASA Technical Reports Server (NTRS)

Whitmore, M.

2004-01-01

The Usability Testing and Analysis Facility (UTAF) is part of the Space Human Factors Laboratory at the NASA Johnson Space Center in Houston, Texas. The facility provides support to the Office of Biological and Physical Research, the Space Shuttle Program, the International Space Station Program, and other NASA organizations. In addition, there are ongoing collaborative research efforts with external businesses and universities. The UTAF provides human factors analysis, evaluation, and usability testing of crew interfaces for space applications. This includes computer displays and controls, workstation systems, and work environments. The UTAF has a unique mix of capabilities, with a staff experienced in both cognitive human factors and ergonomics. The current areas of focus are: human factors applications in emergency medical care and informatics; control and display technologies for electronic procedures and instructions; voice recognition in noisy environments; crew restraint design for unique microgravity workstations; and refinement of human factors processes. This presentation will provide an overview of ongoing activities, and will address how the projects will evolve to meet new space initiatives.

NASA Johnson Space Center Usability Testing and Analysis Facility (WAF) Overview

NASA Technical Reports Server (NTRS)

Whitmore, M.

2004-01-01

The Usability Testing and Analysis Facility (UTAF) is part of the Space Human Factors Laboratory at the NASA Johnson Space Center in Houston, Texas. The facility provides support to the Office of Biological and Physical Research, the Space Shuttle Program, the International Space Station Program, and other NASA organizations. In addition, there are ongoing collaborative research efforts with external businesses and universities. The UTAF provides human factors analysis, evaluation, and usability testing of crew interfaces for space applications. This includes computer displays and controls, workstation systems, and work environments. The UTAF has a unique mix of capabilities, with a staff experienced in both cognitive human factors and ergonomics. The current areas of focus are: human factors applications in emergency medical care and informatics; control and display technologies for electronic procedures and instructions; voice recognition in noisy environments; crew restraint design for unique microgravity workstations; and refinement of human factors processes. This presentation will provide an overview of ongoing activities, and will address how the projects will evolve to meet new space initiatives.

Disgust, but not anger provocation, enhances levator labii superioris activity during exposure to moral transgressions.

PubMed

Whitton, Alexis E; Henry, Julie D; Rendell, Peter G; Grisham, Jessica R

2014-02-01

Physical disgust is elicited by, and amplifies responses to, moral transgressions, suggesting that moral disgust may be a biologically expanded form of physical disgust. However, there is limited research comparing the effects of physical disgust to that of other emotions like anger, making it difficult to determine if the link between disgust and morality is unique. The current research evaluated the specificity of the relationship between disgust and morality by comparing links with anger, using state, physiological and trait measures of emotionality. Participants (N=90) were randomly allocated to have disgust, anger or no emotion induced. Responses to images depicting moral, negative non-moral, and neutral themes were then recorded using facial electromyography. Inducing disgust, but not anger, increased psychophysiological responses to moral themes. Trait disgust, but not trait anger, correlated with levator labii responses to moral themes. These findings provide strong evidence of a unique link between physical disgust and morality. Copyright © 2013 Elsevier B.V. All rights reserved.

A chitin deacetylase of Podospora anserina has two functional chitin binding domains and a unique mode of action.

PubMed

Hoßbach, Janina; Bußwinkel, Franziska; Kranz, Andreas; Wattjes, Jasper; Cord-Landwehr, Stefan; Moerschbacher, Bruno M

2018-03-01

Chitosan is a structurally diverse biopolymer that is commercially derived from chitin by chemical processing, but chitin deacetylases (CDAs) potentially offer a sustainable and more controllable approach allowing the production of chitosans with tailored structures and biological activities. We investigated the CDA from Podospora anserina (PaCDA) which is closely related to Colletotrichum lindemuthianum CDA in the catalytic domain, but unique in having two chitin-binding domains. We produced recombinant PaCDA in Hansenula polymorpha for biochemical characterization and found that the catalytic domain of PaCDA is also functionally similar to C. lindemuthianum CDA, though differing in detail. When studying the enzyme's mode of action on chitin oligomers by quantitative mass-spectrometric sequencing, we found almost all possible sequences up to full deacetylation but with a clear preference for specific products. Deletion muteins lacking one or both CBDs confirmed their proposed function in supporting the enzymatic conversion of the insoluble substrate colloidal chitin. Copyright © 2017. Published by Elsevier Ltd.

Discovery and mechanistic study of a class of protein arginine methylation inhibitors.

PubMed

Feng, You; Li, Mingyong; Wang, Binghe; Zheng, Yujun George

2010-08-26

Protein arginine methylation regulates multiple biological processes such as chromatin remodeling and RNA splicing. Malfunction of protein arginine methyltransferases (PRMTs) is correlated with many human diseases. Thus, small molecule inhibitors of protein arginine methylation are of great potential for therapeutic development. Herein, we report a type of compound that blocks PRMT1-mediated arginine methylation at micromolar potency through a unique mechanism. Most of the discovered compounds bear naphthalene and sulfonate groups and are structurally different from typical PRMT substrates, for example, histone H4 and glycine- and arginine-rich sequences. To elucidate the molecular basis of inhibition, we conducted a variety of kinetic and biophysical assays. The combined data reveal that this type of naphthyl-sulfo (NS) molecule directly targets the substrates but not PRMTs for the observed inhibition. We also found that suramin effectively inhibited PRMT1 activity. These findings about novel PRMT inhibitors and their unique inhibition mechanism provide a new way for chemical regulation of protein arginine methylation.

[Antioxidant activity of cationic whey protein isolate].

PubMed

titova, M E; Komolov, S A; Tikhomirova, N A

2012-01-01

The process of lipid peroxidation (LPO) in biological membranes of cells is carried out by free radical mechanism, a feature of which is the interaction of radicals with other molecules. In this work we investigated the antioxidant activity of cationic whey protein isolate, obtained by the cation-exchange chromatography on KM-cellulose from raw cow's milk, in vitro and in vivo. In biological liquids, which are milk, blood serum, fetal fluids, contains a complex of biologically active substances with a unique multifunctional properties, and which are carrying out a protective, antimicrobial, regenerating, antioxidant, immunomodulatory, regulatory and others functions. Contents of the isolate were determined electrophoretically and by its biological activity. Cationic whey protein isolate included lactoperoxidase, lactoferrin, pancreatic RNase, lysozyme and angeogenin. The given isolate significantly has an antioxidant effect in model experimental systems in vitro and therefore may be considered as a factor that can adjust the intensity of lipid oxidation. In model solutions products of lipid oxidation were obtained by oxidation of phosphatidylcholine by hydrogen peroxide in the presence of a source of iron. The composition of the reaction mixture: 0,4 mM H2O2; 50 mcM of hemin; 2 mg/ml L-alpha-phosphatidylcholine from soybean (Sigma, German). Lipid peroxidation products were formed during the incubation of the reaction mixture for two hours at 37 degrees C. In our studies rats in the adaptation period immediately after isolation from the nest obtained from food given orally native cationic whey protein isolate at the concentration three times higher than in fresh cow's milk. On the manifestation of the antioxidant activity of cationic whey protein isolate in vivo evidence decrease of lipid peroxidation products concentration in the blood of rats from the experimental group receipt whey protein isolate in dos 0,6 mg/g for more than 20% (p<0,05) with oral feeding. Thus, significantly cationic whey protein isolate has an antioxidant effect in model experimental systems, and so can be considered as a factor that can regulate the intensity of lipid oxidation.

Existence and uniqueness of steady state solutions of a nonlocal diffusive logistic equation

NASA Astrophysics Data System (ADS)

Sun, Linan; Shi, Junping; Wang, Yuwen

2013-08-01

In this paper, we consider a dynamical model of population biology which is of the classical Fisher type, but the competition interaction between individuals is nonlocal. The existence, uniqueness, and stability of the steady state solution of the nonlocal problem on a bounded interval with homogeneous Dirichlet boundary conditions are studied.

Encapsulation of cosmetic active ingredients for topical application--a review.

PubMed

Casanova, Francisca; Santos, Lúcia

2016-02-01

Microencapsulation is finding increasing applications in cosmetics and personal care markets. This article provides an overall discussion on encapsulation of cosmetically active ingredients and encapsulation techniques for cosmetic and personal care products for topical applications. Some of the challenges are identified and critical aspects and future perspectives are addressed. Many cosmetics and personal care products contain biologically active substances that require encapsulation for increased stability of the active materials. The topical and transdermal delivery of active cosmetic ingredients requires effective, controlled and safe means of reaching the target site within the skin. Preservation of the active ingredients is also essential during formulation, storage and application of the final cosmetic product. Microencapsulation offers an ideal and unique carrier system for cosmetic active ingredients, as it has the potential to respond to all these requirements. The encapsulated agent can be released by several mechanisms, such as mechanical action, heat, diffusion, pH, biodegradation and dissolution. The selection of the encapsulation technique and shell material depends on the final application of the product, considering physical and chemical stability, concentration, required particle size, release mechanism and manufacturing costs.

Cyclic Dinucleotides in the Scope of the Mammalian Immune System.

PubMed

Mankan, Arun K; Müller, Martina; Witte, Gregor; Hornung, Veit

2017-01-01

First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

Space Product Development (SPD)

NASA Image and Video Library

2003-01-12

Experiments to seek solutions for a range of biomedical issues are at the heart of several investigations that will be hosted by the Commercial Instrumentation Technology Associates (ITA), Inc. Biomedical Experiments (CIBX-2) payload. CIBX-2 is unique, encompassing more than 20 separate experiments including cancer research, commercial experiments, and student hands-on experiments from 10 schools as part of ITA's ongoing University Among the Stars program. Student Marnix Aklian and ITA's Mark Bem prepare biological samples for flight as part of ITA's hands-on student outreach program on STS-95. Similar activities are a part of the CIBX-2 payload. The experiments are sponsored by NASA's Space Product Development Program (SPD).

ZnO-Based Amperometric Enzyme Biosensors

PubMed Central

Zhao, Zhiwei; Lei, Wei; Zhang, Xiaobing; Wang, Baoping; Jiang, Helong

2010-01-01

Nanostructured ZnO with its unique properties could provide a suitable microenvironment for immobilization of enzymes while retaining their biological activity, and thus lead to an expanded use of this nanomaterial for the construction of electrochemical biosensors with enhanced analytical performance. ZnO-based enzyme electrochemical biosensors are summarized in several tables for an easy overview according to the target biosensing analyte (glucose, hydrogen peroxide, phenol and cholesterol), respectively. Moreover, recent developments in enzyme electrochemical biosensors based on ZnO nanomaterials are reviewed with an emphasis on the fabrications and features of ZnO, approaches for biosensor construction (e.g., modified electrodes and enzyme immobilization) and biosensor performances. PMID:22205864

Commercial Instrumentation Technology Associates' Biomedical Experiments

NASA Technical Reports Server (NTRS)

2003-01-01

Experiments to seek solutions for a range of biomedical issues are at the heart of several investigations that will be hosted by the Commercial Instrumentation Technology Associates (ITA), Inc. Biomedical Experiments (CIBX-2) payload. CIBX-2 is unique, encompassing more than 20 separate experiments including cancer research, commercial experiments, and student hands-on experiments from 10 schools as part of ITA's ongoing University Among the Stars program. Student Marnix Aklian and ITA's Mark Bem prepare biological samples for flight as part of ITA's hands-on student outreach program on STS-95. Similar activities are a part of the CIBX-2 payload. The experiments are sponsored by NASA's Space Product Development Program (SPD).

Gammadelta T cells: functional plasticity and heterogeneity.

PubMed

Carding, Simon R; Egan, Paul J

2002-05-01

Gammadelta T cells remain an enigma. They are capable of generating more unique antigen receptors than alphabeta T cells and B cells combined, yet their repertoire of antigen receptors is dominated by specific subsets that recognize a limited number of antigens. A variety of sometimes conflicting effector functions have been ascribed to them, yet their biological function(s) remains unclear. On the basis of studies of gammadelta T cells in infectious and autoimmune diseases, we argue that gammadelta T cells perform different functions according to their tissue distribution, antigen-receptor structure and local microenvironment; we also discuss how and at what stage of the immune response they become activated.

The recent progress of isoxazole in medicinal chemistry.

PubMed

Zhu, Jie; Mo, Jun; Lin, Hong-Zhi; Chen, Yao; Sun, Hao-Peng

2018-05-28

Isoxazole compounds exhibit a wide spectrum of targets and broad biological activities. Developing compounds with heterocycle rings has been one of the trends. The integration of isoxazole ring can offer improved physical-chemical properties. Because of the unique profiles, isoxazole ring becomes a popular moiety in compounds design. In this review article, the major focus has been paid to the applications of isoxazole compounds in treating multiple diseases, including anticancer, antimicrobial, anti-inflammatory, etc. Strategies for compounds design for preclinical, clinical, and FDA approved drugs were discussed. Also, the emphasis has been addressed to the future perspectives and trend for the application. Copyright © 2018 Elsevier Ltd. All rights reserved.

[The recent research progress of chemistry of marine natural products].

PubMed

Shi, Qing-wen; Li, Li-geng; Wang, Yu-fang; Huo, Chang-hong; Zhang, Man-li

2010-10-01

Ocean is a unique and excellent resource that provides a diverse array of intriguing natural products. Marine natural products have demonstrated significant and extremely potent biological activities and have captured the attention of natural products chemists in the past few decades. It is increasingly recognized that a wealth of fascinating natural products and novel chemical entities will play a dominant role in the discovery of useful leads for the development of pharmaceutical agents and provide useful probes to lead to breakthroughs in a variety of life-science fields. This article focused on the research progress of chemistry of marine natural products in recent five years.

Characteristics of silver nanoparticles in vehicles for biological applications.

PubMed

Kejlová, Kristina; Kašpárková, Věra; Krsek, Daniel; Jírová, Dagmar; Kolářová, Hana; Dvořáková, Markéta; Tománková, Kateřina; Mikulcová, Veronika

2015-12-30

Silver nanoparticles (AgNPs) have been used for decades as anti-bacterial agents in various industrial fields such as cosmetics, health industry, food storage, textile coatings and environmental applications, although their toxicity is not fully recognized yet. Antimicrobial and catalytic activity of AgNPs depends on their size as well as structure, shape, size distribution, and physico-chemical environment. The unique properties of AgNPs require novel or modified toxicological methods for evaluation of their toxic potential combined with robust analytical methods for characterization of nanoparticles applied in relevant vehicles, e.g., culture medium with/without serum and phosphate buffered saline. Copyright © 2015 Elsevier B.V. All rights reserved.

Epigenetics Mechanisms in Alzheimer’s disease

PubMed Central

Mastroeni, Diego; Grover, Andrew; Delvaux, Elaine; Whiteside, Charisse; Coleman, Paul D.; Rogers, Joseph

2011-01-01

Epigenetic modifications help orchestrate sweeping developmental, aging, and disease-causing changes in phenotype by altering transcriptional activity in multiple genes spanning multiple biologic pathways. Although previous epigenetic research has focused primarily on dividing cells, particularly in cancer, recent studies have shown rapid, dynamic, and persistent epigenetic modifications in neurons that have significant neuroendocrine, neurophysiologic, and neurodegenerative consequences. Here, we provide a review of the major mechanisms for epigenetic modification and how they are reportedly altered in aging and Alzheimer’s disease (AD). Because of their reach across the genome, epigenetic mechanisms may provide a unique integrative framework for the pathologic diversity and complexity of AD. PMID:21482442

Synthesizing Novel Anthraquinone Natural Product-Like Compounds to Investigate Protein-Ligand Interactions in Both an in Vitro and in Vivo Assay: An Integrated Research-Based Third-Year Chemical Biology Laboratory Course

ERIC Educational Resources Information Center

McKenzie, Nancy; McNulty, James; McLeod, David; McFadden, Meghan; Balachandran, Naresh

2012-01-01

A new undergraduate program in chemical biology was launched in 2008 to provide a unique learning experience for those students interested in this interdisciplinary science. An innovative undergraduate chemical biology laboratory course at the third-year level was developed as a key component of the curriculum. The laboratory course introduces…

Human papillomavirus molecular biology.

PubMed

Harden, Mallory E; Munger, Karl

Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.

tRNA modification profiles of the fast-proliferating cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Chao; Niu, Leilei; Song, Wei

Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In additionmore » to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.« less

Do Advanced Mathematics Skills Predict Success in Biology and Chemistry Degrees?

ERIC Educational Resources Information Center

Adkins, Michael; Noyes, Andrew

2018-01-01

The mathematical preparedness of science undergraduates has been a subject of debate for some time. This paper investigates the relationship between school mathematics attainment and degree outcomes in biology and chemistry across England, a much larger scale of analysis than has hitherto been reported in the literature. A unique dataset which…

The protolobar structure of the human kidney: Its biologic and clinical significance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inke, G.

This book depicts the uniqueness of each kidney as a result of the interaction of the process of nephronogenesis with the random variability of vascular channels within the bounds of a limited space. The fields of anatomy, developmental biology, comparative morphology, embryology, nephrology, pathology, physiology, radiology, and urologic surgery are treated.

Bacteria, Yeast, Worms, and Flies: Exploiting Simple Model Organisms to Investigate Human Mitochondrial Diseases

ERIC Educational Resources Information Center

Rea, Shane L.; Graham, Brett H.; Nakamaru-Ogiso, Eiko; Kar, Adwitiya; Falk, Marni J.

2010-01-01

The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level.…

Crystal structure of Escherichia coli diaminopropionate ammonia-lyase reveals mechanism of enzyme activation and catalysis.

PubMed

Bisht, Shveta; Rajaram, Venkatesan; Bharath, Sakshibeedu R; Kalyani, Josyula Nitya; Khan, Farida; Rao, Appaji N; Savithri, Handanahal S; Murthy, Mathur R N

2012-06-08

Pyridoxal 5'-phosphate (PLP)-dependent enzymes utilize the unique chemistry of a pyridine ring to carry out diverse reactions involving amino acids. Diaminopropionate (DAP) ammonia-lyase (DAPAL) is a prokaryotic PLP-dependent enzyme that catalyzes the degradation of d- and l-forms of DAP to pyruvate and ammonia. Here, we report the first crystal structure of DAPAL from Escherichia coli (EcDAPAL) in tetragonal and monoclinic forms at 2.0 and 2.2 Å resolutions, respectively. Structures of EcDAPAL soaked with substrates were also determined. EcDAPAL has a typical fold type II PLP-dependent enzyme topology consisting of a large and a small domain with the active site at the interface of the two domains. The enzyme is a homodimer with a unique biological interface not observed earlier. Structure of the enzyme in the tetragonal form had PLP bound at the active site, whereas the monoclinic structure was in the apo-form. Analysis of the apo and holo structures revealed that the region around the active site undergoes transition from a disordered to ordered state and assumes a conformation suitable for catalysis only upon PLP binding. A novel disulfide was found to occur near a channel that is likely to regulate entry of ligands to the active site. EcDAPAL soaked with dl-DAP revealed density at the active site appropriate for the reaction intermediate aminoacrylate, which is consistent with the observation that EcDAPAL has low activity under crystallization conditions. Based on the analysis of the structure and results of site-directed mutagenesis, a two-base mechanism of catalysis involving Asp(120) and Lys(77) is suggested.

Modulation of cardiac tissue electrophysiological properties with light-sensitive proteins.

PubMed

Nussinovitch, Udi; Shinnawi, Rami; Gepstein, Lior

2014-04-01

Optogenetics approaches, utilizing light-sensitive proteins, have emerged as unique experimental paradigms to modulate neuronal excitability. We aimed to evaluate whether a similar strategy could be used to control cardiac-tissue excitability. A combined cell and gene therapy strategy was developed in which fibroblasts were transfected to express the light-activated depolarizing channel Channelrhodopsin-2 (ChR2). Patch-clamp studies confirmed the development of a robust inward current in the engineered fibroblasts following monochromatic blue-light exposure. The engineered cells were co-cultured with neonatal rat cardiomyocytes (or human embryonic stem cell-derived cardiomyocytes) and studied using a multielectrode array mapping technique. These studies revealed the ability of the ChR2-fibroblasts to electrically couple and pace the cardiomyocyte cultures at varying frequencies in response to blue-light flashes. Activation mapping pinpointed the source of this electrical activity to the engineered cells. Similarly, diffuse seeding of the ChR2-fibroblasts allowed multisite optogenetics pacing of the co-cultures, significantly shortening their electrical activation time and synchronizing contraction. Next, optogenetics pacing in an in vitro model of conduction block allowed the resynchronization of the tissue's electrical activity. Finally, the ChR2-fibroblasts were transfected to also express the light-sensitive hyperpolarizing proton pump Archaerhodopsin-T (Arch-T). Seeding of the ChR2/ArchT-fibroblasts allowed to either optogentically pace the cultures (in response to blue-light flashes) or completely suppress the cultures' electrical activity (following continuous illumination with 624 nm monochromatic light, activating ArchT). The results of this proof-of-concept study highlight the unique potential of optogenetics for future biological pacemaking and resynchronization therapy applications and for the development of novel anti-arrhythmic strategies.

Differential processing of Arabidopsis ubiquitin-like Atg8 autophagy proteins by Atg4 cysteine proteases

PubMed Central

Woo, Jongchan; Park, Eunsook; Dinesh-Kumar, S. P.

2014-01-01

Autophagy is a highly conserved biological process during which double membrane bound autophagosomes carry intracellular cargo material to the vacuole or lysosome for degradation and/or recycling. Autophagosome biogenesis requires Autophagy 4 (Atg4) cysteine protease-mediated processing of ubiquitin-like Atg8 proteins. Unlike single Atg4 and Atg8 genes in yeast, the Arabidopsis genome contains two Atg4 (AtAtg4a and AtAtg4b) and nine Atg8 (AtAtg8a–AtAtg8i) genes. However, we know very little about specificity of different AtAtg4s for processing of different AtAtg8s. Here, we describe a unique bioluminescence resonance energy transfer-based AtAtg8 synthetic substrate to assess AtAtg4 activity in vitro and in vivo. In addition, we developed a unique native gel assay of superhRLUC catalytic activity assay to monitor cleavage of AtAtg8s in vitro. Our results indicate that AtAtg4a is the predominant protease and that it processes AtAtg8a, AtAtg8c, AtAtg8d, and AtAtg8i better than AtAtg4b in vitro. In addition, kinetic analyses indicate that although both AtAtg4s have similar substrate affinity, AtAtg4a is more active than AtAtg4b in vitro. Activity of AtAtg4s is reversibly inhibited in vitro by reactive oxygen species such as H2O2. Our in vivo bioluminescence resonance energy transfer analyses in Arabidopsis transgenic plants indicate that the AtAtg8 synthetic substrate is efficiently processed and this is AtAtg4 dependent. These results indicate that the synthetic AtAtg8 substrate is used efficiently in the biogenesis of autophagosomes in vivo. Transgenic Arabidopsis plants expressing the AtAtg8 synthetic substrate will be a valuable tool to dissect autophagy processes and the role of autophagy during different biological processes in plants. PMID:24379391

Multi-analysis strategy for metabolism of Andrographis paniculata in rat using liquid chromatography/quadrupole time-of-flight mass spectrometry.

PubMed

Li, Wenlan; Sun, Xiangming; Xu, Ying; Wang, Xuezhi; Bai, Jing; Ji, Yubin

2015-07-01

Compared with chemical drugs, it is a huge challenge to identify active ingredients of multicomponent traditional Chinese medicine (TCM). For most TCMs, metabolism investigation of absorbed constituents is a feasible way to clarify the active material basis. Although Andrographis paniculata (AP) has been extensively researched by domestic and foreign scholars, its metabolism has seldom been fully addressed to date. In this paper, high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was applied to analysis and characterization of AP metabolism in rat urine and feces samples after oral administration of ethanol extract. The differences in metabolites and metabolic pathways between the two biological samples were further compared. The chemical structures of 20 components were tentatively identified from drug-treated biological samples, including six prototype components and 14 metabolites, which underwent such main metabolic pathways as hydrolyzation, hydrogenation, dehydroxylation, deoxygenation, methylation, glucuronidation, sulfonation and sulfation. Two co-existing components were found in urine and feces samples, suggesting that some ingredients' metabolic processes were not unique. This study provides a comprehensive report on the metabolism of AP in rats, which will be helpful for understanding its mechanism. Copyright © 2014 John Wiley & Sons, Ltd.

Recent Advances and Uses of Grape Flavonoids as Nutraceuticals

PubMed Central

Georgiev, Vasil; Ananga, Anthony; Tsolova, Violeta

2014-01-01

Grape is one of the oldest fruit crops domesticated by humans. The numerous uses of grape in making wine, beverages, jelly, and other products, has made it one of the most economically important plants worldwide. The complex phytochemistry of the berry is characterized by a wide variety of compounds, most of which have been demonstrated to have therapeutic or health promoting properties. Among them, flavonoids are the most abundant and widely studied, and have enjoyed greater attention among grape researchers in the last century. Recent studies have shown that the beneficial health effects promoted by consumption of grape and grape products are attributed to the unique mix of polyphenolic compounds. As the largest group of grape polyphenols, flavonoids are the main candidates considered to have biological properties, including but not limited to antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, cardioprotective, neuroprotective, and hepatoprotective activities. Here, we discuss the recent scientific advances supporting the beneficial health qualities of grape and grape-derived products, mechanisms of their biological activity, bioavailability, and their uses as nutraceuticals. The advantages of modern plant cell based biotechnology as an alternative method for production of grape nutraceuticals and improvement of their health qualities are also discussed. PMID:24451310

The demosponge Pseudoceratina purpurea as a new source of fibrous chitin.

PubMed

Żółtowska-Aksamitowska, Sonia; Tsurkan, Mikhail V; Lim, Swee-Cheng; Meissner, Heike; Tabachnick, Konstantin; Shaala, Lamiaa A; Youssef, Diaa T A; Ivanenko, Viatcheslav N; Petrenko, Iaroslav; Wysokowski, Marcin; Bechmann, Nicole; Joseph, Yvonne; Jesionowski, Teofil; Ehrlich, Hermann

2018-06-01

Among marine demosponges (Porifera: Demospongiae), only representatives of the order Verongiida have been recognized to synthetize both biologically active substances as well as scaffolds-like fibrous skeletons made of structural aminopolysaccharide chitin. The unique 3D architecture of such scaffolds open perspectives for their applications in waste treatment, biomimetics and tissue engineering. Here, we focus special attention to the demosponge Pseudoceratina purpurea collected in the coastal waters of Singapore. For the first time the detailed description of the isolation of chitin from the skeleton of this sponge and its identification using diverse bioanalytical tools were carried out. Calcofluor white staining, FTIR analysis, electrospray ionization mass spectrometry (ESI-MS), SEM, and fluorescence microscopy as well as a chitinase digestion assay were applied in order to confirm with strong evidence the finding of alpha-chitin in the skeleton of P. purpurea. We suggest that the discovery of chitin within representatives of Pseudoceratinidae family is a perspective step in evaluation of these verongiid sponges as novel renewable sources for both chitin and biologically active metabolites, which are of prospective use for marine oriented biomedicine and pharmacology, respectively. Copyright © 2018 Elsevier B.V. All rights reserved.

Data-driven inference of network connectivity for modeling the dynamics of neural codes in the insect antennal lobe

PubMed Central

Shlizerman, Eli; Riffell, Jeffrey A.; Kutz, J. Nathan

2014-01-01

The antennal lobe (AL), olfactory processing center in insects, is able to process stimuli into distinct neural activity patterns, called olfactory neural codes. To model their dynamics we perform multichannel recordings from the projection neurons in the AL driven by different odorants. We then derive a dynamic neuronal network from the electrophysiological data. The network consists of lateral-inhibitory neurons and excitatory neurons (modeled as firing-rate units), and is capable of producing unique olfactory neural codes for the tested odorants. To construct the network, we (1) design a projection, an odor space, for the neural recording from the AL, which discriminates between distinct odorants trajectories (2) characterize scent recognition, i.e., decision-making based on olfactory signals and (3) infer the wiring of the neural circuit, the connectome of the AL. We show that the constructed model is consistent with biological observations, such as contrast enhancement and robustness to noise. The study suggests a data-driven approach to answer a key biological question in identifying how lateral inhibitory neurons can be wired to excitatory neurons to permit robust activity patterns. PMID:25165442

A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development.

PubMed

Zhang, Feng; Yu, Jingwen; Yang, Tao; Xu, Dan; Chi, Zhixia; Xia, Yanheng; Xu, Zhiheng

2016-05-27

Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly-associated protein WDR62 are important for neuronal migration during brain development; however, the underlying molecular mechanisms involved remain unclear. We show here that knock-out or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knock-out and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly-associated protein WDR62 and the RAC1-interacting protein POSH (plenty of Src homology). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Lightning under water: Diverse reactive environments and evidence of synergistic effects for material treatment and activation

NASA Astrophysics Data System (ADS)

Levchenko, Igor; Bazaka, Kateryna; Baranov, Oleg; Sankaran, R. Mohan; Nomine, Alexandre; Belmonte, Thierry; Xu, Shuyan

2018-06-01

This focused review aims to reveal and illustrate some unique features of processes triggered by high-density energy applied to liquids and gas-liquid interfaces and to highlight a wide spectrum of their technological applications capable of producing various advantageous effects, ranging from nanosynthesis to biological and medical applications. Plasma, electric discharges, laser, and ultrasound power effects were selected as representative examples of high-density energy and liquid interactions, yet the available possibilities are not limited by these quite different types of power and thus the reader could extrapolate the outlined features and effects to other kinds of powerful impacts. The basic physical mechanisms are briefly reviewed with the aim to familiarize the readers with the potential capabilities of high-density energy processes in liquids. These will be of direct interest to researchers tasked with the development, optimization, and characterization of processes and highly reactive environments for highly controlled transformation of matter in abiotic and biological systems. It could also be highly useful for under- and post-graduate students specializing in the related fields and general physical audience involved in various plasma, materials, energy conversion, and other concurrent research activities.

Space Station Freedom: a unique laboratory for gravitational biology research

NASA Technical Reports Server (NTRS)

Phillips, R. W.; Cowing, K. L.

1993-01-01

The advent of Space Station Freedom (SSF) will provide a permanent laboratory in space with unparalleled opportunities to perform biological research. As with any spacecraft there will also be limitations. It is our intent to describe this space laboratory and present a picture of how scientists will conduct research in this unique environment we call space. SSF is an international venture which will continue to serve as a model for other peaceful international efforts. It is hoped that as the human race moves out from this planet back to the moon and then on to Mars that SSF can serve as a successful example of how things can and should be done.

The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems

PubMed Central

Flores-Santana, Wilmarie; Salmon, Debra J.; Donzelli, Sonia; Switzer, Christopher H.; Basudhar, Debashree; Ridnour, Lisa; Cheng, Robert; Glynn, Sharon A.; Paolocci, Nazareno; Fukuto, Jon M.; Miranda, Katrina M.

2011-01-01

Abstract The importance of nitric oxide in mammalian physiology has been known for nearly 30 years. Similar attention for other nitrogen oxides such as nitroxyl (HNO) has been more recent. While there has been speculation as to the biosynthesis of HNO, its pharmacological benefits have been demonstrated in several pathophysiological settings such as cardiovascular disorders, cancer, and alcoholism. The chemical biology of HNO has been identified as related to, but unique from, that of its redox congener nitric oxide. A summary of these findings as well as a discussion of possible endogenous sources of HNO is presented in this review. Antioxid. Redox Signal. 14, 1659–1674. PMID:21235346

On the application potential of gold nanoparticles in nanoelectronics and biomedicine.

PubMed

Homberger, Melanie; Simon, Ulrich

2010-03-28

Ligand-stabilized gold nanoparticles (AuNPs) are of high interest to research dedicated to future technologies such as nanoelectronics or biomedical applications. This research interest arises from the unique size-dependent properties such as surface plasmon resonance or Coulomb charging effects. It is shown here how the unique properties of individual AuNPs and AuNP assemblies can be used to create new functional materials for applications in a technical or biological environment. While the term technical environment focuses on the potential use of AuNPs as subunits in nanoelectronic devices, the term biological environment addresses issues of toxicity and novel concepts of controlling biomolecular reactions on the surface of AuNPs.

Active multilayered capsules for in vivo bone formation

PubMed Central

Facca, S.; Cortez, C.; Mendoza-Palomares, C.; Messadeq, N.; Dierich, A.; Johnston, A. P. R.; Mainard, D.; Voegel, J.-C.; Caruso, F.; Benkirane-Jessel, N.

2010-01-01

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled. PMID:20160118

Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout.

PubMed

Mendenhall, Jeffrey; Meiler, Jens

2016-02-01

Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods.

Improving Quantitative Structure-Activity Relationship Models using Artificial Neural Networks Trained with Dropout

PubMed Central

Mendenhall, Jeffrey; Meiler, Jens

2016-01-01

Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery (LB-CADD) pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both Enrichment false positive rate (FPR) and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22–46% over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods. PMID:26830599

Designing Anticancer Peptides by Constructive Machine Learning.

PubMed

Grisoni, Francesca; Neuhaus, Claudia S; Gabernet, Gisela; Müller, Alex T; Hiss, Jan A; Schneider, Gisbert

2018-04-21

Constructive (generative) machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a deep machine learning model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on α-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs by transfer learning. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combined computational and biochemical study reveals the importance of electrostatic interactions between the "pH sensor" and the cation binding site of the sodium/proton antiporter NhaA of Escherichia coli.

PubMed

Olkhova, Elena; Kozachkov, Lena; Padan, Etana; Michel, Hartmut

2009-08-15

Sodium proton antiporters are essential enzymes that catalyze the exchange of sodium ions for protons across biological membranes. The crystal structure of NhaA has provided a basis to explore the mechanism of ion exchange and its unique regulation by pH. Here, the mechanism of the pH activation of the antiporter is investigated through functional and computational studies of several variants with mutations in the ion-binding site (D163, D164). The most significant difference found computationally between the wild type antiporter and the active site variants, D163E and D164N, are low pK(a) values of Glu78 making them insensitive to pH. Although in the variant D163N the pK(a) of Glu78 is comparable to the physiological one, this variant cannot demonstrate the long-range electrostatic effect of Glu78 on the pH-dependent structural reorganization of trans-membrane helix X and, hence, is proposed to be inactive. In marked contrast, variant D164E remains sensitive to pH and can be activated by alkaline pH shift. Remarkably, as expected computationally and discovered here biochemically, D164E is viable and active in Na(+)/H(+) exchange albeit with increased apparent K(M). Our results unravel the unique electrostatic network of NhaA that connect the coupled clusters of the "pH sensor" with the binding site, which is crucial for pH activation of NhaA. 2009 Wiley-Liss, Inc.

Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma Brucei.

PubMed

Omar, Ruwida M K; Igoli, John; Gray, Alexander I; Ebiloma, Godwin Unekwuojo; Clements, Carol; Fearnley, James; Ebel, Ru Angeli Edrada; Zhang, Tong; De Koning, Harry P; Watson, David G

2016-01-01

A previous study showed the unique character of Nigerian red propolis from Rivers State, Nigeria (RSN), with regards to chemical composition and activity against Trypanosoma brucei in comparison with other African propolis. To carry out fractionation and biological testing of Nigerian propolis in order to isolate compounds with anti-trypanosomal activity. To compare the composition of the RSN propolis with the composition of Brazilian red propolis. Profiling was carried out using HPLC-UV-ELSD and HPLC-Orbitrap-FTMS on extracts of two samples collected from RSN with data extraction using MZmine software. Isolation was carried out by normal phase and reversed phase MPLC. Elucidation of the compounds with a purity > 95% was performed by 1D/2D NMR HRMS and HRLC-MS(n) . Ten phenolic compounds were isolated or in the case of liquiritigenin partially purified. Data for nine of these correlated with literature reports of known compounds i.e. one isoflavanone, calycosin (1); two flavanones, liquiritigenin (2) and pinocembrin (5); an isoflavan, vestitol (3); a pterocarpan, medicarpin (4); two prenylflavanones, 8-prenylnaringenin (7) and 6-prenylnaringenin (8); and two geranyl flavonoids, propolin D (9) and macarangin (10). The tenth was elucidated as a previously undescribed dihydrobenzofuran (6). The isolated compounds were tested against Trypanosoma brucei and displayed moderate to high activity. Some of the compounds tested had similar activity against wild type T. brucei and two strains displaying pentamidine resistance. Nigerian propolis from RSN has some similarities with Brazilian red propolis. The propolis displayed anti-trypanosomal activity at a potentially useful level. Copyright © 2015 John Wiley & Sons, Ltd.

Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity.

PubMed

Kalb, Suzanne R; Boyer, Anne E; Barr, John R

2015-08-31

Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A-G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin.

Mass Spectrometric Detection of Bacterial Protein Toxins and Their Enzymatic Activity

PubMed Central

Kalb, Suzanne R.; Boyer, Anne E.; Barr, John R.

2015-01-01

Mass spectrometry has recently become a powerful technique for bacterial identification. Mass spectrometry approaches generally rely upon introduction of the bacteria into a matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometer with mass spectrometric recognition of proteins specific to that organism that form a reliable fingerprint. With some bacteria, such as Bacillus anthracis and Clostridium botulinum, the health threat posed by these organisms is not the organism itself, but rather the protein toxins produced by the organisms. One such example is botulinum neurotoxin (BoNT), a potent neurotoxin produced by C. botulinum. There are seven known serotypes of BoNT, A–G, and many of the serotypes can be further differentiated into toxin variants, which are up to 99.9% identical in some cases. Mass spectrometric proteomic techniques have been established to differentiate the serotype or toxin variant of BoNT produced by varied strains of C. botulinum. Detection of potent biological toxins requires high analytical sensitivity and mass spectrometry based methods have been developed to determine the enzymatic activity of BoNT and the anthrax lethal toxins produced by B. anthracis. This enzymatic activity, unique for each toxin, is assessed with detection of the toxin-induced cleavage of strategically designed peptide substrates by MALDI-TOF mass spectrometry offering unparalleled specificity. Furthermore, activity assays allow for the assessment of the biological activity of a toxin and its potential health risk. Such methods have become important diagnostics for botulism and anthrax. Here, we review mass spectrometry based methods for the enzymatic activity of BoNT and the anthrax lethal factor toxin. PMID:26404376

Substitution-inert trinuclear platinum complexes efficiently condense/aggregate nucleic acids and inhibit enzymatic activity**

PubMed Central

Malina, Jaroslav; Farrell, Nicholas P.; Brabec, Viktor

2015-01-01

The trinuclear platinum complexes ([{Pt(NH3)3}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}]6+, TriplatinNC‐A; [{trans-Pt(NH3)2(NH2(CH2)6NH3+)}2-μ-{trans-Pt(NH3)2(NH2(CH2)6NH2)2}]8+, TriplatinNC) belong to a class of biologically active agents that bind to DNA via nonbonding noncovalent (hydrogen bonding, electrostatic) interactions. Charge delocalization (6+ to 8+) in these linear trinuclear platinum complexes results in a high cellular uptake and promising cytotoxic activity in several carcinoma cell lines. We show in the present work with the aid of the methods of biophysical chemistry that in particular TriplatinNC condenses DNA with unprecedented potency which is much higher than that of conventional DNA condensing agents. In addition, in contrast to other DNA condensing agents, both platinum complexes induce aggregation of small transfer RNA molecules. We also demonstrate for the first time that TriplatinNC-A and TriplatinNC in particular completely inhibit DNA transcriptional activity at markedly lower concentration than naturally occurring spermine. Notably, the topoisomerase I-mediated relaxation of supercoiled DNA was inhibited by TriplatinNC-A and TriplatinNC at ~60-fold and ~250-fold lower concentration than that of spermine, respectively. We suggest that the general mechanisms of biological activity of TriplatinNC-A and TriplatinNC may be associated with their unique ability to condense/aggregate nucleic acids with consequent inhibitory effect on crucial enzymatic activities. PMID:25256921

Authentic teaching and learning through synthetic biology

PubMed Central

Kuldell, Natalie

2007-01-01

Synthetic biology is an emerging engineering discipline that, if successful, will allow well-characterized biological components to be predictably and reliably built into robust organisms that achieve specific functions. Fledgling efforts to design and implement a synthetic biology curriculum for undergraduate students have shown that the co-development of this emerging discipline and its future practitioners does not undermine learning. Rather it can serve as the lynchpin of a synthetic biology curriculum. Here I describe educational goals uniquely served by synthetic biology teaching, detail ongoing curricula development efforts at MIT, and specify particular aspects of the emerging field that must develop rapidly in order to best train the next generation of synthetic biologists. PMID:18271945

Relevance of rhodopsin studies for GPCR activation.

PubMed

Deupi, Xavier

2014-05-01

Rhodopsin, the dim-light photoreceptor present in the rod cells of the retina, is both a retinal-binding protein and a G protein-coupled receptor (GPCR). Due to this conjunction, it benefits from an arsenal of spectroscopy techniques that can be used for its characterization, while being a model system for the important family of Class A (also referred to as "rhodopsin-like") GPCRs. For instance, rhodopsin has been a crucial player in the field of GPCR structural biology. Until 2007, it was the only GPCR for which a high-resolution crystal structure was available, so all structure-activity analyses on GPCRs, from structure-based drug discovery to studies of structural changes upon activation, were based on rhodopsin. At present, about a third of currently available GPCR structures are still from rhodopsin. In this review, I show some examples of how these structures can still be used to gain insight into general aspects of GPCR activation. First, the analysis of the third intracellular loop in rhodopsin structures allows us to gain an understanding of the structural and dynamic properties of this region, which is absent (due to protein engineering or poor electron density) in most of the currently available GPCR structures. Second, a detailed analysis of the structure of the transmembrane domains in inactive, intermediate and active rhodopsin structures allows us to detect early conformational changes in the process of ligand-induced GPCR activation. Finally, the analysis of a conserved ligand-activated transmission switch in the transmembrane bundle of GPCRs in the context of the rhodopsin activation cycle, allows us to suggest that the structures of many of the currently available agonist-bound GPCRs may correspond to intermediate active states. While the focus in GPCR structural biology is inevitably moving away from rhodopsin, in other aspects rhodopsin is still at the forefront. For instance, the first studies of the structural basis of disease mutants in GPCRs, or the most detailed analysis of cellular GPCR signal transduction networks using a systems biology approach, have been carried out in rhodopsin. Finally, due again to its unique properties among GPCRs, rhodopsin will likely play an important role in the application of X-ray free electron laser crystallography to time-resolved structural biology in membrane proteins. Rhodopsin, thus, still remains relevant as a model system to study the molecular mechanisms of GPCR activation. This article is part of a Special Issue entitled: Retinal Proteins-You can teach an old dog new tricks. © 2013 Elsevier B.V. All rights reserved.

On the Materials Science of Nature's Arms Race.

PubMed

Liu, Zengqian; Zhang, Zhefeng; Ritchie, Robert O

2018-06-05

Biological material systems have evolved unique combinations of mechanical properties to fulfill their specific function through a series of ingenious designs. Seeking lessons from Nature by replicating the underlying principles of such biological materials offers new promise for creating unique combinations of properties in man-made systems. One case in point is Nature's means of attack and defense. During the long-term evolutionary "arms race," naturally evolved weapons have achieved exceptional mechanical efficiency with a synergy of effective offense and persistence-two characteristics that often tend to be mutually exclusive in many synthetic systems-which may present a notable source of new materials science knowledge and inspiration. This review categorizes Nature's weapons into ten distinct groups, and discusses the unique structural and mechanical designs of each group by taking representative systems as examples. The approach described is to extract the common principles underlying such designs that could be translated into man-made materials. Further, recent advances in replicating the design principles of natural weapons at differing lengthscales in artificial materials, devices and tools to tackle practical problems are revisited, and the challenges associated with biological and bioinspired materials research in terms of both processing and properties are discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-assembled Tunable Photonic Hyper-crystals

DTIC Science & Technology

2014-07-16

a cobalt nanoparticle-based ferrofluid. Unique spectral properties of photonic hyper-crystals lead to extreme sensitivity of the material to...monolayer coatings of cobalt nanoparticles, which should find numerous applications in biological and chemical sensing. 2 Approved for public release...assembly of photonic hyper crystals has been achieved by application of external magnetic field to a cobalt nanoparticle based ferrofluid. Unique spectral

Personomics: The Missing Link in the Evolution from Precision Medicine to Personalized Medicine.

PubMed

Ziegelstein, Roy C

2017-10-16

Clinical practice guidelines have been developed for many common conditions based on data from randomized controlled trials. When medicine is informed solely by clinical practice guidelines, however, the patient is not treated as an individual, but rather a member of a group. Precision medicine, as defined herein, characterizes unique biological characteristics of the individual or of specimens obtained from an individual to tailor diagnostics and therapeutics to a specific patient. These unique biological characteristics are defined by the tools of precision medicine: genomics, proteomics, metabolomics, epigenomics, pharmacogenomics, and other "-omics." Personalized medicine, as defined herein, uses additional information about the individual derived from knowing the patient as a person. These unique personal characteristics are defined by tools known as personomics which takes into account an individual's personality, preferences, values, goals, health beliefs, social support network, financial resources, and unique life circumstances that affect how and when a given health condition will manifest in that person and how that condition will respond to treatment. In this paradigm, precision medicine may be considered a necessary step in the evolution of medical care to personalized medicine, with personomics as the missing link.

Predicting Prostate Cancer Progression At Time of Diagnosis

DTIC Science & Technology

2016-09-01

greater or less than 50% pattern 4—is again arbitrary and may not capture biology adequately [see an unrelated paper we published during the study period...predictor of major upgrading (p=0.02 and p=0.18, respectively). On multinomial analysis, which we feel best reflects the spectrum of biology we are...predictive of outcomes, and that unique insights into tumor biology may be gleaned by analysis of both types of biomarkers. Task 6 As noted

ACE Inhibitory and Antioxidant Activities of Collagen Hydrolysates from the Ribbon Jellyfish (Chrysaora sp.)

PubMed Central

Latiff, Aishah Abd; Gan, Chee-Yuen; Abedin, Md. Zainul; Alias, Abd Karim

2014-01-01

Summary Collagen isolated from the ribbon jellyfish (Chrysaora sp.) was hydrolysed using three different proteases (i.e. trypsin, alcalase and Protamex) to obtain bioactive peptides. Angiotensin-I-converting enzyme (ACE) inhibitory activity and antioxidant activities (i.e. ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity) of the peptides were measured and compared, and the effect of the duration of hydrolysis on the bioactivity (ACE inhibitory and antioxidant activities) of peptides was also evaluated. FRAP activity was the highest in Protamex-induced (25–27 mM) and trypsin-induced hydrolysates (24–26 mM) at 7 and 9 h, respectively. Conversely, hydrolysates produced by trypsin for 1 and 3 h showed the highest DPPH radical scavenging activities (94 and 92%, respectively). Trypsin-induced hydrolysates (at 3 h) also showed the highest ACE inhibitory activity (89%). The peptide sequences with the highest activities were identified using tandem mass spectrometry, and the results show that the hydrolysates had a high content of hydrophobic amino acids as well as unique amino acid sequences, which likely contribute to their biological activities. PMID:27904323

Synthesis, toxicity, biocompatibility, and biomedical applications of graphene and graphene-related materials.

PubMed

Gurunathan, Sangiliyandi; Kim, Jin-Hoi

2016-01-01

Graphene is a two-dimensional atomic crystal, and since its development it has been applied in many novel ways in both research and industry. Graphene possesses unique properties, and it has been used in many applications including sensors, batteries, fuel cells, supercapacitors, transistors, components of high-strength machinery, and display screens in mobile devices. In the past decade, the biomedical applications of graphene have attracted much interest. Graphene has been reported to have antibacterial, antiplatelet, and anticancer activities. Several salient features of graphene make it a potential candidate for biological and biomedical applications. The synthesis, toxicity, biocompatibility, and biomedical applications of graphene are fundamental issues that require thorough investigation in any kind of applications related to human welfare. Therefore, this review addresses the various methods available for the synthesis of graphene, with special reference to biological synthesis, and highlights the biological applications of graphene with a focus on cancer therapy, drug delivery, bio-imaging, and tissue engineering, together with a brief discussion of the challenges and future perspectives of graphene. We hope to provide a comprehensive review of the latest progress in research on graphene, from synthesis to applications.

Synthesis, toxicity, biocompatibility, and biomedical applications of graphene and graphene-related materials

PubMed Central

Gurunathan, Sangiliyandi; Kim, Jin-Hoi

2016-01-01

Graphene is a two-dimensional atomic crystal, and since its development it has been applied in many novel ways in both research and industry. Graphene possesses unique properties, and it has been used in many applications including sensors, batteries, fuel cells, supercapacitors, transistors, components of high-strength machinery, and display screens in mobile devices. In the past decade, the biomedical applications of graphene have attracted much interest. Graphene has been reported to have antibacterial, antiplatelet, and anticancer activities. Several salient features of graphene make it a potential candidate for biological and biomedical applications. The synthesis, toxicity, biocompatibility, and biomedical applications of graphene are fundamental issues that require thorough investigation in any kind of applications related to human welfare. Therefore, this review addresses the various methods available for the synthesis of graphene, with special reference to biological synthesis, and highlights the biological applications of graphene with a focus on cancer therapy, drug delivery, bio-imaging, and tissue engineering, together with a brief discussion of the challenges and future perspectives of graphene. We hope to provide a comprehensive review of the latest progress in research on graphene, from synthesis to applications. PMID:27226713

Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort.

PubMed

Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

2016-11-01

Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR).

Isothermal folding of a light-up bio-orthogonal RNA origami nanoribbon.

PubMed

Torelli, Emanuela; Kozyra, Jerzy Wieslaw; Gu, Jing-Ying; Stimming, Ulrich; Piantanida, Luca; Voïtchovsky, Kislon; Krasnogor, Natalio

2018-05-03

RNA presents intringuing roles in many cellular processes and its versatility underpins many different applications in synthetic biology. Nonetheless, RNA origami as a method for nanofabrication is not yet fully explored and the majority of RNA nanostructures are based on natural pre-folded RNA. Here we describe a biologically inert and uniquely addressable RNA origami scaffold that self-assembles into a nanoribbon by seven staple strands. An algorithm is applied to generate a synthetic De Bruijn scaffold sequence that is characterized by the lack of biologically active sites and repetitions larger than a predetermined design parameter. This RNA scaffold and the complementary staples fold in a physiologically compatible isothermal condition. In order to monitor the folding, we designed a new split Broccoli aptamer system. The aptamer is divided into two nonfunctional sequences each of which is integrated into the 5' or 3' end of two staple strands complementary to the RNA scaffold. Using fluorescence measurements and in-gel imaging, we demonstrate that once RNA origami assembly occurs, the split aptamer sequences are brought into close proximity forming the aptamer and turning on the fluorescence. This light-up 'bio-orthogonal' RNA origami provides a prototype that can have potential for in vivo origami applications.

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network.

PubMed

Qin, Tingting; Matmati, Nabil; Tsoi, Lam C; Mohanty, Bidyut K; Gao, Nan; Tang, Jijun; Lawson, Andrew B; Hannun, Yusuf A; Zheng, W Jim

2014-10-01

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes' Ontology Fingerprints--a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms' corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network

PubMed Central

Qin, Tingting; Matmati, Nabil; Tsoi, Lam C.; Mohanty, Bidyut K.; Gao, Nan; Tang, Jijun; Lawson, Andrew B.; Hannun, Yusuf A.; Zheng, W. Jim

2014-01-01

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes’ Ontology Fingerprints—a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms’ corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. PMID:25063300

Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort

PubMed Central

Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

2016-01-01

Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR). PMID:27759770

Cyanobacterial Metabolite Calothrixins: Recent Advances in Synthesis and Biological Evaluation

PubMed Central

Xu, Su; Nijampatnam, Bhavitavya; Dutta, Shilpa; Velu, Sadanandan E.

2016-01-01

The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotechnological traits. Calothrixins A and B are two cyanobacterial metabolites with a structural assembly of quinoline, quinone, and indole pharmacophores. This review surveys recent advances in the synthesis and evaluation of the biological activities of calothrixins. Due to the low isolation yields from the marine source and the promise this scaffold holds for anticancer and antimicrobial drugs, organic and medicinal chemists around the world have embarked on developing efficient synthetic routes to produce calothrixins. Since the first review appeared in 2009, 11 novel syntheses of calothrixins have been published in the efforts to develop methods that contain fewer steps and higher-yielding reactions. Calothrixins have shown their potential as topoisomerase I poisons for their cytotoxicity in cancer. They have also been observed to target various aspects of RNA synthesis in bacteria. Further investigation into the exact mechanism for their bioactivity is still required for many of its analogs. PMID:26771620

The Envelope Glycoprotein of Friend Spleen Focus-Forming Virus Covalently Interacts with and Constitutively Activates a Truncated Form of the Receptor Tyrosine Kinase Stk

PubMed Central

Nishigaki, Kazuo; Thompson, Delores; Hanson, Charlotte; Yugawa, Takashi; Ruscetti, Sandra

2001-01-01

The Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein, gp55, which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). SFFV gp55 has been shown to interact with the Epo receptor complex, causing constitutive activation of various signal-transducing molecules. When injected into adult mice, SFFV induces a rapid erythroleukemia, with susceptibility being determined by the host gene Fv-2, which was recently shown to be identical to the gene encoding the receptor tyrosine kinase Stk/Ron. Susceptible, but not resistant, mice encode not only full-length Stk but also a truncated form of the kinase, sf-Stk, which may mediate the biological effects of SFFV infection. To determine whether expression of SFFV gp55 leads to the activation of sf-Stk, we expressed sf-Stk, with or without SFFV gp55, in hematopoietic cells expressing the Epo receptor. Our data indicate that sf-Stk interacts with SFFV gp55 as well as gp55P, the biologically active form of the viral glycoprotein, forming disulfide-linked complexes. This covalent interaction, as well as noncovalent interactions with SFFV gp55, results in constitutive tyrosine phosphorylation of sf-Stk and its association with multiple tyrosine-phosphorylated signal-transducing molecules. In contrast, neither Epo stimulation in the absence of SFFV gp55 expression nor expression of a mutant of SFFV that cannot interact with sf-Stk was able to induce tyrosine phosphorylation of sf-Stk or its association with any signal-transducing molecules. Covalent interaction of sf-Stk with SFFV gp55 and constitutive tyrosine phosphorylation of sf-Stk can also be detected in an erythroleukemia cell line derived from an SFFV-infected mouse. Our results suggest that SFFV gp55 may mediate its biological effects in vivo by interacting with and activating a truncated form of the receptor tyrosine kinase Stk. PMID:11483734

Parkin Regulates the Activity of Pyruvate Kinase M2.

PubMed

Liu, Kun; Li, Fanzhou; Han, Haichao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

2016-05-06

Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mucosal melanoma: a clinically and biologically unique disease entity.

PubMed

Carvajal, Richard D; Spencer, Sharon A; Lydiatt, William

2012-03-01

Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made more challenging by its relative rarity. Because of the rarity of MM as a whole, and because of the unique biology and clinical challenges of MM arising from each anatomic location, understanding of this disease and its optimal management remains limited. The impact of various treatment strategies on disease control and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, the retrospective nature of most series, and the lack of a uniform comprehensive staging system for this disease. This article summarizes the clinical, pathologic, and molecular features, and the diagnostic and therapeutic considerations for the management of MM, underscoring the similarities and differences from cutaneous melanoma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces of the head and neck, the anorectal region, and the female genital tract are highlighted.

The biology of amphibians and reptiles in old-growth forests in the Pacific Northwest.

Treesearch

A.P. Blaustein; J.J. Beatty; D.H. Olson; R.M. Storm

1995-01-01

The amphibian and reptile fauna of older forest ecosystems in the Pacific Northwest includes several endemic species, species with unique behavioral and ecological characteristics, and species whose populations have been in decline in recent years. We review the biology of these species and include information on their distinguishing characteristics, behavior, and...

Copper-Zinc Superoxide Dismutase: A Unique Biological "Ligand" for Bioinorganic Studies.

ERIC Educational Resources Information Center

Valentine, Joan Selverstone; de Freitas, Duarte Mota

1985-01-01

Discusses superoxide dismutase (SOD) research and the properties of copper, zinc (Cu, Zn)-SOD. Emphasizes the controversy concerning the role of Cu,Zn-SOD and other SOD enzymes as protective agents in reactions involving dioxygen metabolism, and the properties of Cu, Zn-SOD that make it an interesting biological ligand for physical studies of…

The Secrets of Successful Veteran Biology Teachers: Metaphors of Evolution, Regeneration, and Adaptation

ERIC Educational Resources Information Center

Eilam, Billie

2009-01-01

Voices of veteran junior high and high school biology teachers are seldom heard. Yet, the unique characteristics of this subject-matter may shed some light on veteran teachers' lives in school and their possible contribution to educational systems anywhere. Eight teachers were interviewed, aiming to arrive at their self-perceptions as veteran…

The design of a monopole radiator to investigate the effect of microwave radiation in biological systems.

PubMed

Bigu-del-Blanco, J; Romero-Sierra, C

1977-08-01

The design of a microwave monopole radiator, using a hollow hypodermic needle, is described. This radiator has two unique features. It allows both i) irradiation of deep biological structures by simple needle injection and ii) simultaneous chemotherapic treatment of tissue. The matching characteristics of the monopole in saline solutions are given.

Illuminating Phagocyte Biology: The View from Zebrafish.

PubMed

Huang, Cong; Niethammer, Philipp

2016-07-25

Many phagocyte behaviors, including vascular rolling and adhesion, migration, and oxidative bursting, are better measured in seconds or minutes than hours or days. Zebrafish is ideally suited for imaging such rapid biology within the intact animal. We discuss how this model has revealed unique insights into various aspects of phagocyte physiology. Copyright © 2016 Elsevier Inc. All rights reserved.

An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions

PubMed Central

Sengupta, Raghuvir N.; Van Schie, Sabine N.S.; Giambaşu, George; Dai, Qing; Yesselman, Joseph D.; York, Darrin; Piccirilli, Joseph A.; Herschlag, Daniel

2016-01-01

Biological catalysis hinges on the precise structural integrity of an active site that binds and transforms its substrates and meeting this requirement presents a unique challenge for RNA enzymes. Functional RNAs, including ribozymes, fold into their active conformations within rugged energy landscapes that often contain misfolded conformers. Here we uncover and characterize one such “off-pathway” species within an active site after overall folding of the ribozyme is complete. The Tetrahymena group I ribozyme (E) catalyzes cleavage of an oligonucleotide substrate (S) by an exogenous guanosine (G) cofactor. We tested whether specific catalytic interactions with G are present in the preceding E•S•G and E•G ground-state complexes. We monitored interactions with G via the effects of 2′- and 3′-deoxy (–H) and −amino (–NH2) substitutions on G binding. These and prior results reveal that G is bound in an inactive configuration within E•G, with the nucleophilic 3′-OH making a nonproductive interaction with an active site metal ion termed MA and with the adjacent 2′-OH making no interaction. Upon S binding, a rearrangement occurs that allows both –OH groups to contact a different active site metal ion, termed MC, to make what are likely to be their catalytic interactions. The reactive phosphoryl group on S promotes this change, presumably by repositioning the metal ions with respect to G. This conformational transition demonstrates local rearrangements within an otherwise folded RNA, underscoring RNA's difficulty in specifying a unique conformation and highlighting Nature's potential to use local transitions of RNA in complex function. PMID:26567314

An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions.

PubMed

Sengupta, Raghuvir N; Van Schie, Sabine N S; Giambaşu, George; Dai, Qing; Yesselman, Joseph D; York, Darrin; Piccirilli, Joseph A; Herschlag, Daniel

2016-01-01

Biological catalysis hinges on the precise structural integrity of an active site that binds and transforms its substrates and meeting this requirement presents a unique challenge for RNA enzymes. Functional RNAs, including ribozymes, fold into their active conformations within rugged energy landscapes that often contain misfolded conformers. Here we uncover and characterize one such "off-pathway" species within an active site after overall folding of the ribozyme is complete. The Tetrahymena group I ribozyme (E) catalyzes cleavage of an oligonucleotide substrate (S) by an exogenous guanosine (G) cofactor. We tested whether specific catalytic interactions with G are present in the preceding E•S•G and E•G ground-state complexes. We monitored interactions with G via the effects of 2'- and 3'-deoxy (-H) and -amino (-NH(2)) substitutions on G binding. These and prior results reveal that G is bound in an inactive configuration within E•G, with the nucleophilic 3'-OH making a nonproductive interaction with an active site metal ion termed MA and with the adjacent 2'-OH making no interaction. Upon S binding, a rearrangement occurs that allows both -OH groups to contact a different active site metal ion, termed M(C), to make what are likely to be their catalytic interactions. The reactive phosphoryl group on S promotes this change, presumably by repositioning the metal ions with respect to G. This conformational transition demonstrates local rearrangements within an otherwise folded RNA, underscoring RNA's difficulty in specifying a unique conformation and highlighting Nature's potential to use local transitions of RNA in complex function. © 2015 Sengupta et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Guodong; Department of Abdominal Surgery, Cancer treatment center, Fourth Affiliated Hospital of Harbin Medical University, Harbin; Lin, Wenwei

Farnesoid X receptor (FXR) is a ligand-activated nuclear receptor and serves as a key regulator to maintain health of the liver and intestine. Bile acids are endogenous ligands of FXR, and there are increasing efforts to identify FXR modulators to serve as biological probes and/or pharmaceutical agents. Natural FXR ligands isolated from plants may serve as models to synthesize novel FXR modulators. In this study, we demonstrated that epigallocatechin-3-gallate (EGCG), a major tea catechin, specifically and dose-dependently activates FXR. In addition, EGCG induced FXR target gene expression in vitro. Surprisingly, in a co-activator (SRC2) recruitment assay, we found that EGCGmore » does not recruit SRC2 to FXR, but it dose-dependently inhibits recruitment of SRC2 to FXR (IC{sub 50}, 1 μM) by GW6064, which is a potent FXR synthetic ligand. In addition, EGCG suppressed FXR target gene expression induced by either GW4064 or chenodeoxycholic acid in vitro. Furthermore, wild-type and FXR knockout mice treated with an acute dose of EGCG had induced mRNA expression in a subset of FXR target genes in the intestine but not in the liver. In conclusion, EGCG is a unique modulator of FXR in the intestine and may serve as an important model for future development of FXR modulators. -- Highlights: ► Epigallocatechin-3-gallate (EGCG) is a unique farnesoid X receptor (FXR) modulator. ► EGCG activates FXR by itself, but inhibits FXR transactivation by other agonists. ► Low concentration of EGCG activates FXR in mouse intestine but not liver. ► EGCG activates FXR to induce a subset of FXR target genes in mouse intestine.« less

B. F. Skinner and G. H. Mead: on biological science and social science.

PubMed Central

Blackman, D E

1991-01-01

Skinner's contributions to psychology provide a unique bridge between psychology conceptualized as a biological science and psychology conceptualized as a social science. Skinner focused on behavior as a naturally occurring biological phenomenon of interest in its own right, functionally related to surrounding events and, in particular (like phylogenesis), subject to selection by its consequences. This essentially biological orientation was further enhanced by Skinner's emphasis on the empirical foundations provided by laboratory-based experimental analyses of behavior, often with nonhuman subjects. Skinner's theoretical writings, however, also have affinity with the traditions of constructionist social science. The verbal behavior of humans is said to be subject, like other behavior, to functional analyses in terms of its environment, in this case its social context. Verbal behavior in turn makes it possible for us to relate to private events, a process that ultimately allows for the development of consciousness, which is thus said to be a social product. Such ideas make contact with aspects of G. H. Mead's social behaviorism and, perhaps of more contemporary impact in psychology, L. Vygotsky's general genetic law of cultural development. Failure to articulate both the biological and the social science aspects of Skinner's theoretical approach to psychology does a disservice to his unique contribution to a discipline that remains fragmented between two intellectual traditions. PMID:2037828

On Beyond Star Trek, the Role of Synthetic Biology in Nasa's Missions

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

The time has come to for NASA to exploit the nascent field of synthetic biology in pursuit of its mission, including aeronautics, earth science, astrobiology and notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particularly space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement and the 2012 team has expanded the use of synthetic biology to estimate the potential for life in the clouds of other planets (http://2012.igem.org/Team:Stanford-Brown; http://www.calacademy.org/sciencetoday/igem-competition/). More recent projects from the Stanford-Brown team have expanded our ideas of how synthetic biology can aid NASA's missions from "Synthetic BioCommunication" (http://2013.igem.org/Team:Stanford-Brown) to a "Biodegradable UAS (drone)" in collaboration with Spelman College (http://2014.igem.org/Team:StanfordBrownSpelman#SBS%20iGEM) and most recently, "Self-Folding Origami" (http://2015.igem.org/Team:Stanford-Brown), the winner of the 2015 award for Manufacturing.

Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication.

PubMed

Cousins, Emily; Nicholas, John

2014-01-01

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the second identified human gammaherpesvirus. Like its relative Epstein-Barr virus, HHV-8 is linked to B-cell tumors, specifically primary effusion lymphoma and multicentric Castleman's disease, in addition to endothelial-derived KS. HHV-8 is unusual in its possession of a plethora of "accessory" genes and encoded proteins in addition to the core, conserved herpesvirus and gammaherpesvirus genes that are necessary for basic biological functions of these viruses. The HHV-8 accessory proteins specify not only activities deducible from their cellular protein homologies but also novel, unsuspected activities that have revealed new mechanisms of virus-host interaction that serve virus replication or latency and may contribute to the development and progression of virus-associated neoplasia. These proteins include viral interleukin-6 (vIL-6), viral chemokines (vCCLs), viral G protein-coupled receptor (vGPCR), viral interferon regulatory factors (vIRFs), and viral antiapoptotic proteins homologous to FLICE (FADD-like IL-1β converting enzyme)-inhibitory protein (FLIP) and survivin. Other HHV-8 proteins, such as signaling membrane receptors encoded by open reading frames K1 and K15, also interact with host mechanisms in unique ways and have been implicated in viral pathogenesis. Additionally, a set of micro-RNAs encoded by HHV-8 appear to modulate expression of multiple host proteins to provide conditions conducive to virus persistence within the host and could also contribute to HHV-8-induced neoplasia. Here, we review the molecular biology underlying these novel virus-host interactions and their potential roles in both virus biology and virus-associated disease.

Exploring possible mechanisms of action for the nanotoxicity and protein binding of decorated nanotubes: interpretation of physicochemical properties from optimal QSAR models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esposito, Emilio Xavier, E-mail: emilio@exeResearch.com; The Chem21 Group, Inc., 1780 Wilson Drive, Lake Forest, IL 60045; Hopfinger, Anton J., E-mail: hopfingr@gmail.com

2015-10-01

Carbon nanotubes have become widely used in a variety of applications including biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is increasingly an area of focus and concern. While previous studies have focused on the gross mechanisms of action relating to nanomaterials interacting with biological entities, this study proposes detailed mechanisms of action, relating to nanotoxicity, for a series of decorated (functionalized) carbon nanotube complexes based on previously reported QSAR models. Possible mechanisms of nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase, chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production) have been extracted frommore » the corresponding optimized QSAR models. The molecular features relevant to each of the endpoint respective mechanism of action for the decorated nanotubes are also discussed. Based on the molecular information contained within the optimal QSAR models for each nanotoxicity endpoint, either the decorator attached to the nanotube is directly responsible for the expression of a particular activity, irrespective of the decorator's 3D-geometry and independent of the nanotube, or those decorators having structures that place the functional groups of the decorators as far as possible from the nanotube surface most strongly influence the biological activity. These molecular descriptors are further used to hypothesize specific interactions involved in the expression of each of the six biological endpoints. - Highlights: • Proposed toxicity mechanism of action for decorated nanotubes complexes • Discussion of the key molecular features for each endpoint's mechanism of action • Unique mechanisms of action for each of the six biological systems • Hypothesized mechanisms of action based on QSAR/QNAR predictive models.« less

Electromagnetic information transfer through aqueous system.

PubMed

Foletti, Alberto; Ledda, Mario; Lolli, Maria Grazia; Grimaldi, Settimio; Lisi, Antonella

2017-01-01

Several beneficial effects of the electromagnetic information transfer through aqueous system (EMITTAS) procedure have previously been reported in vitro. The clinical potential of this procedure has also started to be evaluated. Information flow in biological systems can be investigated through chemical and molecular approaches or by a biophysical approach focused on endogenous electrodynamic activities. Electromagnetic signals are endogenously generated at different levels of the biological organization and, likely, play an active role in synchronizing internal cell function or local/systemic adaptive response. Consequently, each adaptive response can be described by its specific electromagnetic pattern and, therefore, correlates with a unique and specific electromagnetic signature. A biophysical procedure synchronously integrating the EMITTAS procedure has already been applied for the treatment of articular pain, low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic kidney disease, refractory gynecological infections, minor anxiety and depression disorders. This clinical strategy involves a single treatment, since the EMITTAS procedure allows the patient to continue his/her own personal treatment at home by means of self-administration of the recorded aqueous system. A significant and long-lasting improvement has been reported, showing a potential beneficial use of this biophysical procedure in the management of common illnesses in an efficient, effective and personalized way. Data from recent studies suggest that aqueous systems may play a key role in providing the basis for recording, storing, transferring and retrieving clinically effective quanta of biological information. These features likely enable to trigger local and systemic self-regulation and self-regeneration potential of the organism.

Functional Identification of Valerena-1,10-diene Synthase, a Terpene Synthase Catalyzing a Unique Chemical Cascade in the Biosynthesis of Biologically Active Sesquiterpenes in Valeriana officinalis*

PubMed Central

Yeo, Yun-Soo; Nybo, S. Eric; Chittiboyina, Amar G.; Weerasooriya, Aruna D.; Wang, Yan-Hong; Góngora-Castillo, Elsa; Vaillancourt, Brieanne; Buell, C. Robin; DellaPenna, Dean; Celiz, Mary Dawn; Jones, A. Daniel; Wurtele, Eve Syrkin; Ransom, Nick; Dudareva, Natalia; Shaaban, Khaled A.; Tibrewal, Nidhi; Chandra, Suman; Smillie, Troy; Khan, Ikhlas A.; Coates, Robert M.; Watt, David S.; Chappell, Joe

2013-01-01

Valerian is an herbal preparation from the roots of Valeriana officinalis used as an anxiolytic and sedative and in the treatment of insomnia. The biological activities of valerian are attributed to valerenic acid and its putative biosynthetic precursor valerenadiene, sesquiterpenes, found in V. officinalis roots. These sesquiterpenes retain an isobutenyl side chain whose origin has been long recognized as enigmatic because a chemical rationalization for their biosynthesis has not been obvious. Using recently developed metabolomic and transcriptomic resources, we identified seven V. officinalis terpene synthase genes (VoTPSs), two that were functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. The reaction products for two of the sesquiterpene synthases exhibiting root-specific expression were characterized by a combination of GC-MS and NMR in comparison to the terpenes accumulating in planta. VoTPS7 encodes for a synthase that biosynthesizes predominately germacrene C, whereas VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene. Using a yeast expression system, specific labeled [13C]acetate, and NMR, we investigated the catalytic mechanism for VoTPS1 and provide evidence for the involvement of a caryophyllenyl carbocation, a cyclobutyl intermediate, in the biosynthesis of valerena-1,10-diene. We suggest a similar mechanism for the biosynthesis of several other biologically related isobutenyl-containing sesquiterpenes. PMID:23243312

Functional identification of valerena-1,10-diene synthase, a terpene synthase catalyzing a unique chemical cascade in the biosynthesis of biologically active sesquiterpenes in Valeriana officinalis.

PubMed

Yeo, Yun-Soo; Nybo, S Eric; Chittiboyina, Amar G; Weerasooriya, Aruna D; Wang, Yan-Hong; Góngora-Castillo, Elsa; Vaillancourt, Brieanne; Buell, C Robin; DellaPenna, Dean; Celiz, Mary Dawn; Jones, A Daniel; Wurtele, Eve Syrkin; Ransom, Nick; Dudareva, Natalia; Shaaban, Khaled A; Tibrewal, Nidhi; Chandra, Suman; Smillie, Troy; Khan, Ikhlas A; Coates, Robert M; Watt, David S; Chappell, Joe

2013-02-01

Valerian is an herbal preparation from the roots of Valeriana officinalis used as an anxiolytic and sedative and in the treatment of insomnia. The biological activities of valerian are attributed to valerenic acid and its putative biosynthetic precursor valerenadiene, sesquiterpenes, found in V. officinalis roots. These sesquiterpenes retain an isobutenyl side chain whose origin has been long recognized as enigmatic because a chemical rationalization for their biosynthesis has not been obvious. Using recently developed metabolomic and transcriptomic resources, we identified seven V. officinalis terpene synthase genes (VoTPSs), two that were functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. The reaction products for two of the sesquiterpene synthases exhibiting root-specific expression were characterized by a combination of GC-MS and NMR in comparison to the terpenes accumulating in planta. VoTPS7 encodes for a synthase that biosynthesizes predominately germacrene C, whereas VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene. Using a yeast expression system, specific labeled [(13)C]acetate, and NMR, we investigated the catalytic mechanism for VoTPS1 and provide evidence for the involvement of a caryophyllenyl carbocation, a cyclobutyl intermediate, in the biosynthesis of valerena-1,10-diene. We suggest a similar mechanism for the biosynthesis of several other biologically related isobutenyl-containing sesquiterpenes.

[Biological disturbances during the lupus-associated pancreatitis: case report].

PubMed

Sayagh, Sanae; Benchekroun, Leila; Bouabdellah, Mounya; Jaouhar, Nezha; El Aoufi, Farida; El Oufir, Fatiha; Alaoui, Meryem; Adnaoui, Mohammed; Chabraoui, Layachi

2015-01-01

We report in this paper the case of female patient, hypertriglyceridemia associated with milky serum and hyperglycemia have been the alarm signal of a lupus-associated pancreatitis, the confirmation of this entity was done with elevated rate of serum lipase activity. It is about a 33 years age female. She has as unique antecedent a lupus diagnosed on January of the same. The patient was admitted on august 2013 for another episode of lupus associated to the lower lamb edema with a rate of C3 at 0.4 g/L (0.82-1,93) and C4 at 0.05 g/L (0.15-0.57). One day after the beginning of the corticotherapy, the patient presented hyperthermia, ataxis and behavior troubles, epigastric and articular pains and vomiting. Biochemical tests found hyperglycemia at 38.9 mmol/L (3.9-6.1), dyslipidemia with hypertriglyceridemia at 15.7 mmol/L (0.3-1.7) and total cholesterol rate at 5.2 mmol/L (<5.2) associated with milky serum. Haematological tests objective normocytic normochromic anemia with 81 g/L of hemoglobin, lymphopenia at 0.88 G/L and normal platelet rate. Lupus associated pancreatitis was suggested and confirmed biologically with an hyperlipasemia at 180 UI/L (8-78) and radiologicaly with the image of focal hepatic steatosis. We conclude that on the presence of lupus, gastrointestinal and/or biological signs must motivate the measurement of the serum lipase activity as quickly as possible to assess the diagnosis of lupus-associated pancreatitis.