共查询到20条相似文献,搜索用时 31 毫秒
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2.
Rubina P. Shaikh Viness Pillay Yahya E. Choonara Lisa C. du Toit Valence M. K. Ndesendo Priya Bawa Shivaan Cooppan 《AAPS PharmSciTech》2010,11(1):441-459
Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the
movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical
applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is
a behavior that can be utilized to prepare ‘smart’ drug delivery systems. Stimuli-responsive or ‘smart’ polymers are polymers
that upon exposure to small changes in the environment undergo rapid changes in their microstructure. A stimulus, such as
a change in pH or temperature, thus serves as a trigger for the release of drug from membranous drug delivery systems that
are formulated from stimuli-responsive polymers. This article has sought to review the use of stimuli-responsive polymers
that have found application in membranous drug delivery systems. Polymers responsive to pH and temperature have been extensively
addressed in this review since they are considered the most important stimuli that may be exploited for use in drug delivery,
and biomedical applications such as in tissue engineering. In addition, dual-responsive and glucose-responsive membranes have
been also addressed as membranes responsive to diverse stimuli. 相似文献
3.
Anne Vinther Morant Kirsten Jørgensen Bodil Jørgensen Winnie Dam Carl Erik Olsen Birger Lindberg Møller Søren Bak 《Metabolomics : Official journal of the Metabolomic Society》2007,3(3):383-398
Plants produce a plethora of secondary metabolites which constitute a wealth of potential pharmaceuticals, pro-vitamins, flavours,
fragrances, colorants and toxins as well as a source of natural pesticides. Many of these valuable compounds are only synthesized
in exotic plant species or in concentrations too low to facilitate commercialization. In some cases their presence constitutes
a health hazard and renders the crops unsuitable for consumption. Metabolic engineering is a powerful tool to alter and ameliorate
the secondary metabolite composition of crop plants and gain new desired traits. The interplay of a multitude of biosynthetic
pathways and the possibility of metabolic cross-talk combined with an incomplete understanding of the regulation of these
pathways, explain why metabolic engineering of plant secondary metabolism is still in its infancy and subject to much trial
and error. Cyanogenic glucosides are ancient defense compounds that release toxic HCN upon tissue disruption caused e.g. by
chewing insects. The committed steps of the cyanogenic glucoside biosynthetic pathway are encoded by three genes. This unique
genetic simplicity and the availability of the corresponding cDNAs have given cyanogenic glucosides pioneering status in metabolic
engineering of plant secondary metabolism. In this review, lessons learned from metabolic engineering of cyanogenic glucosides
in Arabidopsis thaliana (thale cress), Nicotiana tabacum cv Xanthi (tobacco), Manihot esculenta Crantz (cassava) and Lotus japonicus (bird’s foot trefoil) are presented. The importance of metabolic channelling of toxic intermediates as mediated by metabolon
formation in avoiding unintended metabolic cross-talk and unwanted pleiotropic effects is emphasized. Likewise, the potential
of metabolic engineering of plant secondary metabolism as a tool to elucidate, for example, the impact of secondary metabolites
on plant–insect interactions is demonstrated. 相似文献
4.
Plant–fungal symbiotic associations are ubiquitously distributed in natural plant communities. Besides the well-studied mycorrhizal
symbiosis and grass systemic clavicipitaceous endophytes, recently, nonsystemic and horizontally transmitted fungal endophytes
serving as plant symbionts have been increasingly recognized. Pure culture isolation and culture-independent molecular methods
indicate that all parts of healthy plant tissues potentially harbor diverse and previously unknown fungal lineages. Limited
evidence also supports a hypothesis that endophytic mycobiota dynamics may have a role in evolution of plants. High variability
or “balanced antagonism” can be generally characterized with host–endophyte interactions, which implies that the outcome of
symbiotic interactions can fall within a continuum ranging from mutualism to commensalism, and ultimately pathogenicity. Despite
this complicated system, admittedly, fungal endophytes really endow the host with an extended phenotype. Accumulating facts
illustrate that plant nutrition acquisition, metabolism, and stress tolerance may be strengthened or modulated via fungal
symbionts. Piriformospora indica, a member of the order Sebacinales, simultaneously confers host resistance to biotic and abiotic stress. The ecological relevance
of other fungal groups, including foliar endophytes, root dark septate endophytes (DSEs), some opportunistic and avirulent
microsymbionts (for example, Trichoderma and Fusarium), and even uncultured fungi structurally and physiologically integrated with host tissues, are also being deeply exploited.
Production of bioactive metabolites by fungi, overexpression of stress-related enzymes, and induced resistance in hosts upon
fungal colonization are responsible for direct or indirect beneficial effects to hosts. More knowledge of endophyte-mediated
enhancement of host performance and fitness will offer alternatively valuable strategies for plant cultivation and breeding.
Meanwhile, with unprecedented loss of biodiversity, discovery of indigenously novel symbiotic endophytes from natural habitats
is urgently needed. In addition, we present some approaches and suggestions for studying host–endophyte interactions. 相似文献
5.
Kenneth D. Carr 《Neurochemical research》1996,21(11):1455-1467
The incentive-motivating effects of external stimuli are dependent, in part, upon the internal need state of the organism.
The increased rewarding efficacy of food as a function of energy deficit, for example, has obvious adaptive value. The enhancement
of food reward extends, however, to drugs of abuse and electrical brain stimulation, probably due to a shared neural substrate.
Research reviewed in this paper uses lateral hypothalamic electrical stimulation to probe the sensitivity of the brain reward
system and investigate mechanisms through which metabolic need, induced by chronic food restriction and streptozotocin-induced
diabetes, sensitizes this system. Results indicate that sensitivity to rewarding brain stimulation varies inversely with declining
body weight. The effect is not mimicked by pharmacological glucoprivation or lipoprivation in ad libitum fed animals; sensitization
appears to depend on persistent metabolic need or adipose depletion. While the literature suggests elevated plasma corticosterone
as a peripheral trigger of reward sensitization, sensitization was not reversed by meal-induced or pharmacological suppression
of plasma corticosterone. Centrally, reward sensitization is mediated by opioid receptors, since the effect is reversed by
intracerebroventricular (i.c.v.) infusion of naltrexone, TCTAP (μ antagonist) and nor-binaltorphimine (κ antagonist). The
fact that these same treatments, as well as i.c.v. infusion of dynorphin A antiserum, block the feeding response to lateral
hypothalamic stimulation suggests that feeding and reward sensitization are mediated by a common opioid mechanism. Using in
vitro autoradiography, radioimmunoassays and a solution hybridization mRNA assay, brain regional μ and κ opioid receptor binding,
levels of prodynorphin-derived peptides, and prodynorphin mRNA, respectively, were measured in food-restricted and diabetic
rats. Changes that could plausibly be involved in reward sensitization are discussed, with emphasis on the increased dynorphin
A1–8 and prodynorphin mRNA levels in lateral hypothalamic neurons that innervate the pontine parabrachial nucleus, where μ binding
decreased and κ binding increased. Finally, the possible linkage between metabolic need and activation of a brain opioid mechanism
is discussed, as is evidence supporting the relevance of these findings to drug abuse.
Special issue dedicated to Dr. Eric J. Simon. 相似文献
6.
Drug interactions are important causes of both unexpected toxic and therapeutic effects. Adverse reactions due to drug interaction are proportional to the number of drugs given and the duration of administration. Although drug interactions may be beneficial, they are most often recognized when they increase mortality or morbidity. The frequency of adverse drug interactions in clinical practice makes it mandatory for physicians to know the drugs and mechanisms involved.A drug may potentiate or antagonize the effects of another drug by direct chemical or physical combination, by altering gastrointestinal absorption, by influencing metabolism, transport, or renal clearance, by changing the activity of a drug at its receptor site, or by modifying the patient''s response to the drug by a variety of means.This article stresses the importance of avoiding multible drug therapy. When such treatment is unavoidable, patients must be carefully observed for evidence of intensified or diminished drug effect. Only this permits the detection and prevention of untoward drug interactions. 相似文献
7.
Emergence of drug resistance is a major problem in the treatment of many diseases including tuberculosis. To tackle the problem
from a wholistic perspective, it is essential to understand the molecular mechanisms by which bacteria acquire drug resistance
using a systems approach. Availability of genome-scale data of expression profiles under different drug exposed conditions
and protein–protein interactions, makes it feasible to reconstruct and analyze systems-level models. A number of proteins
involved in different resistance mechanisms, referred to as the resistome are identified from literature. The interaction
of the drug directly with the resistome is unable to explain most resistance processes adequately, including that of increased
mutations in the target’s binding site. We recently hypothesized that some communication might exist from the drug environment
to the resistome to trigger emergence of drug resistance. We report here a network based approach to identify most plausible
paths of such communication in Mycobacterium tuberculosis. Networks capturing both structural and functional linkages among various proteins were weighted based on gene expression
profiles upon exposure to specific drugs and betweenness centrality of the interactions. Our analysis suggests that different
drug targets and hence different drugs could trigger the resistome to different extents and through different routes. The
identified paths correlate well with the mechanisms known through experiment. Some examples of the top ranked hubs in multiple
drug specific networks are PolA, FadD1, CydA, a monoxygenase and GltS, which could serve as co-targets, that could be inhibited
in order to retard resistance related communication in the cell. 相似文献
8.
Silvana Ficarra Francesco Misiti Annamaria Russo Cristiana Carelli-Alinovi Ersilia Bellocco Davide Barreca Giuseppina Laganà Ugo Leuzzi Giovanni Toscano Bruno Giardina Antonio Galtieri Ester Tellone 《Biochimie》2013
Carbamazepine (CBZ) is an iminostilbene derivative commonly used for treatment of neuralgic pain and bipolar affective disorders. CBZ blood levels of treated patients are within the range of micromolar concentrations and therefore, significant interactions of this drug with erythrocytes are very likely. Moreover, the lipid domains of the cell membrane are believed to be one of the sites where iminostilbene derivatives exert their effects. The present study aimed to deeply characterize CBZ effects on erythrocytes, in order to identify extra and/or cytosolic cell targets. Our results indicate that erythrocyte morphological changes promoted by the drug, may be triggered by an alteration in band 3 functionality i.e. at the level of anionic flux. In addition, from a metabolic point of view this perturbation could be considered, at least in part, as a beneficial event because it could favour the CO2 elimination. 相似文献
9.
《International biodeterioration & biodegradation》2005,55(2):99-102
Inhibiting the growth of mold fungi on cellulose-based building materials may be achievable through the use of azole-based antimycotics. Azoles were variably effective against mold fungi that are frequently found on wood and wood products. Unseasoned southern yellow pine specimens that were dip-treated with varying concentrations of eight azoles were evaluated for their ability to resist mold infestation when challenged with Aspergillus niger, Penicillium chrysogenum, and Trichoderma viride spores. Minimal fungicidal concentrations (MFC90) were determined to be 0.016% for thiabendazole and 0.043% for voriconazole, the most efficacious azoles against the challenge fungi. We conclude that thiabendazole or voriconazole may be used alone or in combination to inhibit mold fungi on unseasoned pine. 相似文献
10.
Drug-drug metabolic interactions can result in unwanted side effects, including reduced drug efficacy and formation of toxic metabolic intermediates. In this work, thermodynamic constraints on non-equilibrium metabolite concentrations are used to reveal the biochemical interactions between the metabolic pathways of ethanol and acetaminophen (N-acetyl-p-aminophenol), two drugs known to interact unfavorably. It is known that many reactions of these pathways are coupled to the central energy metabolic reactions through a number of metabolites and the cellular redox potential. Based on these observations, a metabolic network model has been constructed and a database of thermodynamic properties for all participating metabolites and reactions has been compiled. Constraint-based computational analysis of the feasible metabolite concentrations reveals that the non-toxic pathways for APAP metabolism and the pathway for detoxifying N-acetyl-p-benzoquinoneimine (NAPQI) are inhibited by network interactions with ethanol metabolism. These results point to the potential utility of thermodynamically based profiling of metabolic network interactions in screening of drug candidates and analysis of potential toxicity. 相似文献
11.
Marvin J. Miller Helen Zhu Yanping Xu Chunrui Wu Andrew J. Walz Anne Vergne John M. Roosenberg Garrett Moraski Albert A. Minnick Julia McKee-Dolence Jingdan Hu Kelley Fennell E. Kurt Dolence Li Dong Scott Franzblau Francois Malouin Ute Möllmann 《Biometals》2009,22(1):61-75
Pathogenic microbes rapidly develop resistance to antibiotics. To keep ahead in the “microbial war”, extensive interdisciplinary
research is needed. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial
permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (ie., beta-lactamase)
and even induction of efflux mechanisms. A combination of chemical syntheses, microbiological and biochemical studies demonstrate
that the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development
of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective
iron-chelating compounds called siderophores. Our studies, and those of others, demonstrate that siderophores and analogs
can be used for iron transport-mediated drug delivery (“Trojan Horse” antibiotics) and induction of iron limitation/starvation
(Development of new agents to block iron assimilation). Recent extensions of the use of siderophores for the development of
novel potent and selective anticancer agents are also described. 相似文献
12.
The aim of the investigation was to prepare and characterize wheat germ agglutinin(WGA)-conjugated poly(d,l-lactic-co-glycolic) acid nanoparticles encapsulating mometasone furoate (MF) as a model drug and assess changes in its fate in terms
of cellular interactions. MF loaded nanoparticles were prepared using emulsion–solvent evaporation technique. WGA-conjugation
was done by carbodiimide coupling method. The nanoparticles were characterized for size, zeta potential, entrapment efficiency
and in-vitro drug release. The intracellular uptake of nanoparticles, drug cellular levels, and anti-proliferative activity studies of
wheat germ agglutinin-conjugated and unconjugated nanoparticles were assessed on alveolar epithelial (A549) cells to establish
cellular interactions. Prepared nanoparticles were spherical with 10–15 μg/mg of WGA conjugated on nanoparticles. The size
of nanoparticles increased after conjugation and drug entrapment and zeta potential reduced from 78 ± 5.5% to 60 ± 2.5% and
−15.3 ± 1.9 to −2.59 ± 2.1 mV respectively after conjugation. From the cellular drug concentration–time plot, AUC was found
to be 0.4745, 0.6791 and 1.24 for MF, MF-nanoparticles and wheat germ agglutinin-MF-nanoparticles respectively. The in-vitro antiproliferative activity was improved and prolonged significantly after wheat germ agglutinin-conjugation. The results
conclusively demonstrate improved availability and efficacy of antiasthmatic drug in alveolar epithelial cell lines. Hence,
a drug once formulated as mucoadhesive nanoparticles and incorporated in dry powder inhaler formulation may be used for targeting
any segment of lungs for more improved therapeutic response in other lung disorders as well. 相似文献
13.
Gómez-Lechón MJ Donato T Ponsoda X Castell JV 《Alternatives to laboratory animals : ATLA》2003,31(3):257-265
Drug metabolism is the major determinant of drug clearance, and the factor most frequently responsible for inter-individual differences in drug pharmacokinetics. The expression of drug metabolising enzymes shows significant interspecies differences, and variability among human individuals (polymorphic or inducible enzymes) makes the accurate prediction of the metabolism of a new compound in humans difficult. Several key issues need to be addressed at the early stages of drug development to improve drug candidate selection: a) how fast the compound will be metabolised; b) what metabolites will be formed (metabolic profile); c) which enzymes are involved and to what extent; and d) whether drug metabolism will be affected directly (drug-drug interactions) or indirectly (enzyme induction) by the administered compound. Drug metabolism studies are routinely performed in laboratory animals, but they are not sufficiently accurate to predict the metabolic profiles of drugs in humans. Many of these issues can now be addressed by the use of relevant human in vitro models, which speed up the selection of new candidate drugs. Human hepatocytes are the closest in vitro model to the human liver, and they are the only model which can produce a metabolic profile of a drug which is very similar to that found in vivo. However, the use of human hepatocytes is restricted, because limited access to suitable tissue samples prevents their use in high throughput screening systems. The pharmaceutical industry has made great efforts to develop fast and reliable in vitro models to overcome these drawbacks. Comparative studies on liver microsomes and cells from animal species, including humans, are very useful for demonstrating species differences in the metabolic profile of given drug candidates, and are of great value in the judicious and justifiable selection of animal species for later pharmacokinetic and toxicological studies. Cytochrome P450 (CYP)-engineered cells (or microsomes from CYP-engineered cells, for example, Supersomes) have made the identification of the CYPs involved in the metabolism of a drug candidate more straightforward and much easier. However, the screening of compounds acting as potential CYP inducers can only be conducted in cellular systems fully capable of transcribing and translating CYP genes. 相似文献
14.
Bin Cao Paul D. Majors Bulbul Ahmed Ryan S. Renslow Crystal P. Silvia Liang Shi Staffan Kjelleberg Jim K. Fredrickson Haluk Beyenal 《Environmental microbiology》2012,14(11):2901-2910
Biofilms are core to a range of biological processes, including the bioremediation of environmental contaminants. Within a biofilm population, cells with diverse genotypes and phenotypes coexist, suggesting that distinct metabolic pathways may be expressed based on the local environmental conditions in a biofilm. However, metabolic responses to local environmental conditions in a metabolically active biofilm interacting with environmental contaminants have never been quantitatively elucidated. In this study, we monitored the spatiotemporal metabolic responses of metabolically active Shewanella oneidensis MR‐1 biofilms to U(VI) (uranyl, UO2 2+) and Cr(VI) (chromate, CrO4 2?) using non‐invasive nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) approaches to obtain insights into adaptation in biofilms during biofilm‐contaminant interactions. While overall biomass distribution was not significantly altered upon exposure to U(VI) or Cr(VI), MRI and spatial mapping of the diffusion revealed localized changes in the water diffusion coefficients in the biofilms, suggesting significant contaminant‐induced changes in structural or hydrodynamic properties during bioremediation. Finally, we quantitatively demonstrated that the metabolic responses of biofilms to contaminant exposure are spatially stratified, implying that adaptation in biofilms is custom‐developed based on local microenvironments. 相似文献
15.
Terence A. Ketter Mark A. Frye Gabriela Corá-Locatelli Timothy A. Kimbrell Robert M. Post 《Cellular and molecular neurobiology》1999,19(4):511-532
1. The mood stabilizers lithium, carbamazepine (CBZ), and valproate (VPA), have differing pharmacokinetics, structures, mechanisms of action, efficacy spectra, and adverse effects. Lithium has a low therapeutic index and is renally excreted and hence has renally-mediated but not hepatically-mediated drug–drug interactions.2. CBZ has multiple problematic drug–drug interactions due to its low therapeutic index, metabolism primarily by a single isoform (CYP3A3/4), active epoxide metabolite, susceptibility to CYP3A3/4 or epoxide hydrolase inhibitors, and ability to induce drug metabolism (via both cytochrome P450 oxidation and conjugation). In contrast, VPA has less prominent neurotoxicity and three principal metabolic pathways, rendering it less susceptible to toxicity due to inhibition of its metabolism. However, VPA can increase plasma concentrations of some drugs by inhibiting metabolism and increase free fractions of certain medications by displacing them from plasma proteins.3. Older anticonvulsants such as phenobarbital and phenytoin induce hepatic metabolism, may produce toxicity due to inhibition of their metabolism, and have not gained general acceptance in the treatment of primary psychiatric disorders.4. The newer anticonvulsants felbamate, lamotrigine, topiramate, and tiagabine have different hepatically-mediated drug–drug interactions, while the renally excreted gabapentin lacks hepatic drug–drug interactions but may have reduced bioavailability at higher doses.5. Investigational anticonvulsants such as oxcarbazepine, vigabatrin, and zonisamide appear to have improved pharmacokinetic profiles compared to older agents.6. Thus, several of the newer anticonvulsants lack the problematic drug-drug interactions seen with older agents, and some may even (based on their mechanisms of action and preliminary preclinical and clinical data) ultimately prove to have novel psychotropic effects. 相似文献
16.
Interactions between mitochondrial and nuclear gene products that underlie eukaryotic energy metabolism can cause the fitness effects of mutations in one genome to be conditional on variation in the other genome. In ectotherms, the effects of these interactions are likely to depend upon the thermal environment, because increasing temperature accelerates molecular rates. We find that temperature strongly modifies the pleiotropic phenotypic effects of an incompatible interaction between a Drosophila melanogaster polymorphism in the nuclear-encoded, mitochondrial tyrosyl-transfer (t)RNA synthetase and a D. simulans polymorphism in the mitochondrially encoded tRNATyr. The incompatible mitochondrial–nuclear genotype extends development time, decreases larval survivorship, and reduces pupation height, indicative of decreased energetic performance. These deleterious effects are ameliorated when larvae develop at 16° and exacerbated at warmer temperatures, leading to complete sterility in both sexes at 28°. The incompatible genotype has a normal metabolic rate at 16° but a significantly elevated rate at 25°, consistent with the hypothesis that inefficient energy metabolism extends development in this genotype at warmer temperatures. Furthermore, the incompatibility decreases metabolic plasticity of larvae developed at 16°, indicating that cooler development temperatures do not completely mitigate the deleterious effects of this genetic interaction. Our results suggest that the epistatic fitness effects of metabolic mutations may generally be conditional on the thermal environment. The expression of epistatic interactions in some environments, but not others, weakens the efficacy of selection in removing deleterious epistatic variants from populations and may promote the accumulation of incompatibilities whose fitness effects will depend upon the environment in which hybrids occur. 相似文献
17.
Li AP 《Chemico-biological interactions》2007,168(1):16-29
The recent developments in the isolation, culturing, and cryopreservation of human hepatocytes, and the application of the cells in drug development are reviewed. Recent advances include the improvement of cryopreservation procedures to allow cell attachment, thereby extending the use of the cells to assays that requires prolong culturing such as enzyme induction studies. Applications of human hepatocytes in drug development include the evaluation of metabolic stability, metabolite profiling and identification, drug-drug interaction potential, and hepatotoxic potential. The use of intact human hepatocytes, because of the complete, undisrupted metabolic pathways and cofactors, allows the development of data more relevant to humans in vivo than tissue fractions such as human liver microsomes. Incorporation of key in vivo factors with the intact hepatocytes in vitro may help predictive human in vivo drug properties. For instance, evaluation of drug metabolism and drug-drug interactions with intact human hepatocytes in 100% human serum may eliminate the need to determine in vivo intracellular concentrations for the extrapolation of in vitro data to in vivo. Co-culturing of hepatocytes and nonhepatic primary cells from other organs in the integrated discrete multiple organ co-culture (IdMOC) may allow the evaluation of multiple organ interactions in drug metabolism and drug toxicity. In conclusion, human hepatocytes represent a critical experimental model for drug development, allowing early evaluation of human drug properties to guide the design and selection of drug candidates with a high probability of clinical success. 相似文献
18.
Pharmacometabonomic phenotyping reveals different responses to xenobiotic intervention in rats 总被引:5,自引:0,他引:5
Li H Ni Y Su M Qiu Y Zhou M Qiu M Zhao A Zhao L Jia W 《Journal of proteome research》2007,6(4):1364-1370
In conventional pharmacological studies, intersubject differences within an animal strain are normally neglected, leading to variations in pharmacological outcomes in response to the same stimulus. Using two classical experimental models, the Streptozotocin (STZ)-induced diabetic model of Wistar rats and the high-energy, diet-induced obesity model of Sprague-Dawley rats, we demonstrate that the different outcomes of STZ or diet intervention are closely associated with variation in predose (baseline) urinary metabolic profiles of the rats. The pharmacometabonomic analysis of predose metabolic profiles indicates that the intersubject difference is, to a great extent, associated with gut-microbiota, which predisposes different pathophysiological outcomes upon diet alteration or chemical stimulus. We hypothesize that there may exist an important association between observations from these two models and the obese/diabetic human population in that subtle variations in metabolic phenotype may predetermine different systems' responses to xenobiotic perturbation, ultimately leading to varied pathophysiological processes. Results from two independent models also suggest that the pharmacometabonomics approach is of great importance in the study of pharmacology and clinical drug evaluations, where endogenous metabolite signatures of predose individuals should be taken into consideration to minimize intersubject difference and the resulting variation in the postdose pharmacological outcomes. 相似文献
19.
Sakshi Shrivastava Ch. V. Siva Kumar Reddy Sharmila S. Mande 《Journal of biosciences》2010,35(3):351-364
Genomic islands (GIs) are regions in the genome which are believed to have been acquired via horizontal gene transfer events
and are thus likely to be compositionally distinct from the rest of the genome. Majority of the genes located in a GI encode
a particular function. Depending on the genes they encode, GIs can be classified into various categories, such as ‘metabolic
islands’, ‘symbiotic islands’, ‘resistance islands’, ‘pathogenicity islands’, etc. The computational process for GI detection
is known and many algorithms for the same are available. We present a new method termed as Improved N-mer based Detection
of Genomic Islands Using Sequence-clustering (INDeGenIUS) for the identification of GIs. This method was applied to 400 completely
sequenced species belonging to proteobacteria. Based on the genes encoded in the identified GIs, the GIs were grouped into
6 categories: metabolic islands, symbiotic islands, resistance islands, secretion islands, pathogenicity islands and motility
islands. Several new islands of interest which had previously been missed out by earlier algorithms were picked up as GIs
by INDeGenIUS. The present algorithm has potential application in the identification of functionally relevant GIs in the large
number of genomes that are being sequenced. Investigation of the predicted GIs in pathogens may lead to identification of
potential drug/vaccine candidates. 相似文献
20.
Phytochemical research has revealed that organic sulfur-containing compounds (OSCs) from Allium species exert biological effects, that might be beneficial in the treatment or prevention of a range of diseases, such as
infections, cardiovascular and metabolic affections, cancers and related indispositions. Focusing physiological activities
of these compounds in the context of cancer, it became clear from both epidemiological studies in men and experimental studies
in diverse models, that the OSCs have a strong potential to prevent or to treat cancers even with selectivity against non-neoplastic
cells. Though underlying mechanisms are not yet fully understood, several parts of their modes and mechanisms of action were
elucidated: Pivotal molecular targets of as well chemoprevention as chemotherapy are metabolic, transporter or repair enzymes
strongly affecting cell death, proliferation and formation of metastases. Accordingly effects are not restricted to the run
of cell death programs, but they moreover comprise the strongly interdepending immune and inflammatory systems. Respectively,
several hypotheses exist which are based on chemical properties of sulfur as the “pharmacophor” of the compounds appearing
in up to ten different oxidation states (−2 to +6). Hence compounds can undergo redox-reactions and electrostatic interactions,
making reactive oxygen species (ROS) a key feature of their mechanisms of action. 相似文献