VARIDT 1.0: variability of drug transporter database

Abstract The absorption, distribution and excretion of drugs are largely determined by their transporters (DTs), the variability of which has thus attracted considerable attention. There are three aspects of variability: epigenetic regulation and genetic polymorphism, species/tissue/disease-specific DT abundances, and exogenous factors modulating DT activity. The variability data of each aspect are essential for clinical study, and a collective consideration among multiple aspects becomes crucial in precision medicine. However, no database is constructed to provide the comprehensive data of all aspects of DT variability. Herein, the Variability of Drug Transporter Database (VARIDT) was introduced to provide such data. First, 177 and 146 DTs were confirmed, for the first time, by the transporting drugs approved and in clinical/preclinical, respectively. Second, for the confirmed DTs, VARIDT comprehensively collected all aspects of their variability (23 947 DNA methylations, 7317 noncoding RNA/histone regulations, 1278 genetic polymorphisms, differential abundance profiles of 257 DTs in 21 781 patients/healthy individuals, expression of 245 DTs in 67 tissues of human/model organism, 1225 exogenous factors altering the activity of 148 DTs), which allowed mutual connection between any aspects. Due to huge amount of accumulated data, VARIDT made it possible to generalize characteristics to reveal disease etiology and optimize clinical treatment, and is freely accessible at: https://db.idrblab.org/varidt/ and http://varidt.idrblab.net/.

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An RNA-centric view on gut Bacteroidetes

Biological Chemistry ◽

10.1515/hsz-2020-0230 ◽

2020 ◽

Vol 402 (1) ◽

pp. 55-72

Author(s):

Daniel Ryan ◽

Gianluca Prezza ◽

Alexander J. Westermann

Keyword(s):

Noncoding Rna ◽

Case Reports ◽

Model Organism ◽

Global Gene Expression ◽

Host Cells ◽

Human Gut ◽

Open Questions ◽

Obligate Anaerobic ◽

Bacterial Rna ◽

Rna Biology

AbstractBacteria employ noncoding RNAs to maintain cellular physiology, adapt global gene expression to fluctuating environments, sense nutrients, coordinate their interaction with companion microbes and host cells, and protect themselves against bacteriophages. While bacterial RNA research has made fundamental contributions to biomedicine and biotechnology, the bulk of our knowledge of RNA biology stems from the study of a handful of aerobic model species. In comparison, RNA research is lagging in many medically relevant obligate anaerobic species, in particular the numerous commensal bacteria comprising our gut microbiota. This review presents a guide to RNA-based regulatory mechanisms in the phylum Bacteroidetes, focusing on the most abundant bacterial genus in the human gut, Bacteroides spp. This includes recent case reports on riboswitches, an mRNA leader, cis- and trans-encoded small RNAs (sRNAs) in Bacteroides spp., and a survey of CRISPR-Cas systems across Bacteroidetes. Recent work from our laboratory now suggests the existence of hundreds of noncoding RNA candidates in Bacteroides thetaiotaomicron, the emerging model organism for functional microbiota research. Based on these collective observations, we predict mechanistic and functional commonalities and differences between Bacteroides sRNAs and those of other model bacteria, and outline open questions and tools needed to boost Bacteroidetes RNA research.

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The Influence of Bee Venom Melittin on the Functioning of the Immune System and the Contractile Activity of the Insect Heart—A Preliminary Study

Toxins ◽

10.3390/toxins11090494 ◽

2019 ◽

Vol 11 (9) ◽

pp. 494 ◽

Cited By ~ 5

Author(s):

Jan Lubawy ◽

Arkadiusz Urbański ◽

Lucyna Mrówczyńska ◽

Eliza Matuszewska ◽

Agata Światły-Błaszkiewicz ◽

...

Keyword(s):

Immune System ◽

Contractile Activity ◽

Model Organism ◽

Dependent Manner ◽

Physiological Studies ◽

Almost All ◽

First Time ◽

Dose Dependent ◽

Positive Effect

Melittin (MEL) is a basic polypeptide originally purified from honeybee venom. MEL exhibits a broad spectrum of biological activity. However, almost all studies on MEL activity have been carried out on vertebrate models or cell lines. Recently, due to cheap breeding and the possibility of extrapolating the results of the research to vertebrates, insects have been used for various bioassays and comparative physiological studies. For these reasons, it is valuable to examine the influence of melittin on insect physiology. Here, for the first time, we report the immunotropic and cardiotropic effects of melittin on the beetle Tenebrio molitor as a model insect. After melittin injection at 10−7 M and 10−3 M, the number of apoptotic cells in the haemolymph increased in a dose-dependent manner. The pro-apoptotic action of MEL was likely compensated by increasing the total number of haemocytes. However, the injection of MEL did not cause any changes in the percent of phagocytic haemocytes or in the phenoloxidase activity. In an in vitro bioassay with a semi-isolated Tenebrio heart, MEL induced a slight chronotropic-positive effect only at a higher concentration (10−4 M). Preliminary results indicated that melittin exerts pleiotropic effects on the functioning of the immune system and the endogenous contractile activity of the heart. Some of the induced responses in T. molitor resemble the reactions observed in vertebrate models. Therefore, the T. molitor beetle may be a convenient invertebrate model organism for comparative physiological studies and for the identification of new properties and mechanisms of action of melittin and related compounds.

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Temperature shock tolerance and heat shock proteins in Arctic freshwater ostracod Candona rectangulata - preliminary results

Polish Polar Research ◽

10.2478/v10183-012-0011-6 ◽

2012 ◽

Vol 33 (2) ◽

pp. 199-206 ◽

Cited By ~ 2

Author(s):

Barbara Wojtasik ◽

Dorota Kuczyńska-Wiśnik

Keyword(s):

Heat Shock ◽

Heat Shock Proteins ◽

Protein Profile ◽

Model Organism ◽

Arctic Water ◽

Temperature Shock ◽

Temperature Changes ◽

Preliminary Results ◽

Shock Proteins ◽

First Time

Temperature shock tolerance and heat shock proteins in Arctic freshwater ostracod Candona rectangulata - preliminary results Candona rectangulata is an ostracod species common in cold (<15°C) shallow freshwater Arctic water bodies. This species is useful in palaeolimnological studies because only few known autecological data can be applied in reconstructions of palaeoclimate. Particular attention was paid to the temperature, which is the basic factor determining the geographic range of a species. In this study a wide tolerance of C. rectangulata to the temperature was demonstrated for the first time. Its high tolerance to the temperature changes seems to be based on induction of set of proteins belonging to the family of heat shock proteins. Using PAGE-SDS electrophoresis variation in the protein profile of non-model organism undergoing stress in the field (South Spitsbergen, near Stanisław Siedlecki Polish Polar Station) and in laboratory cultures was presented. These results could explain the eurythermic range of C. rectangulata and its good adaptation to the environmental conditions which normally do not exist in Arctic freshwater ponds.

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Physiological Heterogeneity Triggers Sibling Conflict Mediated by the Type VI Secretion System in an Aggregative Multicellular Bacterium

mBio ◽

10.1128/mbio.01645-17 ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 14

Author(s):

Vera Troselj ◽

Anke Treuner-Lange ◽

Lotte Søgaard-Andersen ◽

Daniel Wall

Keyword(s):

Model Organism ◽

Secretion System ◽

Gliding Motility ◽

Sibling Conflict ◽

Type Vi Secretion System ◽

Collective Behaviors ◽

Type Vi Secretion ◽

Physiological Differences ◽

First Time ◽

Physiological Heterogeneity

ABSTRACTA hallmark of social microorganisms is their ability to engage in complex and coordinated behaviors that depend on cooperative and synchronized actions among many cells. For instance, myxobacteria use an aggregation strategy to form multicellular, spore-filled fruiting bodies in response to starvation. One barrier to the synchronization process is physiological heterogeneity within clonal populations. How myxobacteria cope with these physiological differences is poorly understood. Here, we investigated the interactions between closely related but physiologically distinctMyxococcus xanthuspopulations. We used a genetic approach to create amino acid auxotrophs and tested how they interact with a parental prototroph strain. Importantly, we found that auxotrophs were killed by their prototroph siblings when the former were starved for amino acids but not when grown on rich medium or when both strains were starved. This antagonism depended on the type VI secretion system (T6SS) as well as gliding motility; in particular, we identified the effector-immunity pair (TsxEI) as the mediator of this killing. This sibling antagonism resulted from lower levels of the TsxI immunity protein in the starved population. Thus, when starving auxotrophs were mixed with nonstarving prototrophs, the auxotrophs were susceptible to intoxication by the TsxE effector delivered by the T6SS from the prototrophs. Furthermore, our results suggested that homogeneously starving populations have reduced T6SS activity and, therefore, do not antagonize each other. We conclude that heterogeneous populations ofM. xanthususe T6SS-dependent killing to eliminate starving or less-fit cells, thus facilitating the attainment of homeostasis within a population and the synchronization of behaviors.IMPORTANCESocial bacteria employ elaborate strategies to adapt to environmental challenges. One means to prepare for unpredictable changes is for clonal populations to contain individuals with diverse physiological states. These subpopulations will differentially respond to new environmental conditions, ensuring that some cells will better adapt. However, for social bacteria physiological heterogeneity may impede the ability of a clonal population to synchronize their behaviors. By using a highly cooperative and synchronizable model organism,M. xanthus, we asked how physiological differences between interacting siblings impacted their collective behaviors. Physiological heterogeneity was experimentally designed such that one population starved while the other grew when mixed. We found that these differences led to social conflict where more-fit individuals killed their less-fit siblings. For the first time, we report that the T6SS nanoweapon mediates antagonism between siblings, resulting in myxobacterial populations becoming more synchronized to conduct social behaviors.

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Un-‘Egg’-Plored: Characterisation of Embryonation in the Whipworm Model Organism Trichuris muris

Frontiers in Tropical Diseases ◽

10.3389/fitd.2021.790311 ◽

2021 ◽

Vol 2 ◽

Author(s):

Ruth Forman ◽

Frederick A. Partridge ◽

David B. Sattelle ◽

Kathryn J. Else

Keyword(s):

Control Strategies ◽

Quantitative Description ◽

Model Organism ◽

Efficacy Rate ◽

Trichuris Muris ◽

Modelling Studies ◽

Basic Biology ◽

The Impact ◽

First Time ◽

High Possibility

Trichuris muris, is the murine parasite and widely deployed model for the human whipworm Trichuris trichiura, a parasite that infects around 500 million people globally. Trichuriasis is a classical disease of poverty with a cycle of re-infection due to the continual exposure of humans, particularly children, to infective eggs, which contaminate the soil in endemic areas. Indeed, modelling studies of trichuriasis have demonstrated that the low efficacy rate of current anthelmintics combined with the high possibility of re-infection from the reservoir of infective eggs within the environment, mean that the elimination of morbidity due to trichuriasis is unlikely to occur. Despite the importance of the infective egg stage in the perpetuation of infections, understanding the biology of the Trichuris ova has been neglected for decades. Here we perform experiments to assess the impact of temperature on the embryonation process of T. muris eggs and describe in detail the stages of larval development within these eggs. In keeping with the early works performed in the early 1900s, we show that the embryonation of T. muris is accelerated by an elevation in temperature, up to 37°C above which eggs do not fully develop and become degenerate. We extend these data to provide a detailed description of T. muris egg development with clear images depicting the various stages of development. To the best of our knowledge we have, for the first time, described the presence of birefringent granules within egg-stage larvae, as well as providing a qualitative and quantitative description of a motile larval stage prior to quiescence within the egg. These experiments are the first step towards a better understanding of the basic biology which underlies the process of egg embryonation. With the threat of elevation in global temperatures, the accelerated embryonation rate we observe at higher temperatures may have important consequences for parasite transmission rates and prospective modelling studies. In addition, a deeper understanding of the Trichuris ova may allow the development of novel control strategies targeting the egg stage of Trichuris in the environment as an adjunct to MDA.

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OMAMO: orthology-based model organism selection

10.1101/2021.11.04.467067 ◽

2021 ◽

Author(s):

Alina Nicheperovich ◽

Adrian M Altenhoff ◽

Christophe Dessimoz ◽

Sina Majidian

Keyword(s):

Literature Review ◽

Biological Process ◽

Model Organism ◽

Complex Model ◽

Model Systems ◽

Human Model ◽

Model Organisms ◽

Human Biology ◽

Traditional Model ◽

Ethical Concerns

The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are higher animals. To address these issues, we have developed Orthologous Matrix and Model Organisms, a software and a website that provide the user with the best simple organism for research into a biological process of interest based on orthologous relationships between the human and the species. The outputs provided by the database were supported by a systematic literature review.

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A Physiological Characterization in Controlled Bioreactors Reveals a Novel Survival Strategy for Debaryomyces hansenii at High Salinity and Confirms its Halophilic Behavior

10.1101/2020.01.10.901843 ◽

2020 ◽

Cited By ~ 2

Author(s):

Clara Navarrete ◽

August T. Frost ◽

Laura Ramos-Moreno ◽

Mette R. Krum ◽

José L. Martínez

Keyword(s):

Carbon Metabolism ◽

Debaryomyces Hansenii ◽

Model Organism ◽

Central Carbon Metabolism ◽

Culture Conditions ◽

Physiological Characterization ◽

Behavioural Patterns ◽

Central Carbon ◽

First Time

AbstractDebaryomyces hansenii is traditionally described as a halotolerant non-conventional yeast, being the model organism for the study of osmo- and salt tolerance mechanisms in eukaryotic systems for the past 30 years.However, unravelling of D. hansenii’s biotechnological potential has always been difficult due to the persistent limitations in the availability of efficient molecular tools described for this yeast. Additionally, there is a lack of consensus and contradictory information along the recent years that limits a comprehensive understanding of its central carbon metabolism, mainly due to a lack of physiological studies in controlled and monitored environments. Moreover, there is controversy about the diversity in the culture conditions (media composition, temperature and pH among others) used by different groups, which makes it complicated when trying to get significant conclusions and behavioural patterns.In this work, we present for the first time a physiological characterization of D. hansenii in batch cultivations using highly instrumented and controlled lab-scale bioreactors. Our findings contribute to a more complete picture of the central carbon metabolism and the external pH influence on the yeast ability to tolerate high Na+ and K+ concentrations. Finally, the controversial halophilic/halotolerant character of this yeast is further clarified.

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Complete Genome Sequence of Enterobacter roggenkampii Strain KQ-01, Isolated from Bacterial Wilt-Resistant Mulberry Cultivar YS283

Plant Disease ◽

10.1094/pdis-07-20-1468-a ◽

2021 ◽

pp. PDIS-07-20-1468

Author(s):

Yinan Zhou ◽

Hongyu Yang ◽

Jiping Liu

Keyword(s):

Ribosomal Rna ◽

Bacterial Wilt ◽

Noncoding Rna ◽

Gc Content ◽

Wilt Disease ◽

Circular Chromosome ◽

Protein Coding ◽

First Time ◽

Rna Genes ◽

Single Circular Chromosome

An Enterobacter roggenkampii strain, named KQ-01, was isolated for the first time from the diseased roots of the bacterial wilt-resistant mulberry (Morus atropurpurea) cultivar YS283 in the western part of Guangxi Zhuang Autonomous Region, China. E. roggenkampii KQ-01 was characterized by a single, circular chromosome of 4,667,006 bp in size, with a 56.16% GC content. In total, 4,396 genes were annotated, of which 4,281 were assigned as protein-coding genes. In addition, 25 ribosomal RNA, 84 transfer RNA, and 6 noncoding RNA genes as well as 34 pseudogenes were predicted. The resource herein presented will help to explore the pathogenetic mechanisms of mulberry wilt disease caused by genus Enterobacter.

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Identification of Functional Noncoding RNA-encoded Proteins on Lipid Droplets

10.1101/2020.04.10.036160 ◽

2020 ◽

Author(s):

Ting Huang ◽

Adekunle T. Bamigbade ◽

Shimeng Xu ◽

Yaqin Deng ◽

Kang Xie ◽

...

Keyword(s):

Oleic Acid ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Noncoding Rna ◽

Cell Fractionation ◽

Protein Database ◽

Endogenous Expression ◽

Small Proteins ◽

Encoded Proteins ◽

First Time

AbstractOver the past decade, great progress in sequencing technologies and computational biology has revealed that the majority of the mammalian genome considered to be noncoding is rich in functional elements able to produce proteins. Many RNA molecules, mis-annotated as noncoding, actually harbor small open reading frames that are predicted to code for proteins. Some of those proteins have been verified to play critical roles in multiple biological processes. The lipid droplet (LD) is a unique cellular organelle, conserved from bacteria to humans, and is closely associated with cellular lipid metabolism and metabolic disorders. No noncoding RNA-coded proteins have been identified on LDs. Here, for the first time, we searched the organelle for their presence. After the enrichment of small proteins of LDs isolated from myoblasts, we used mass spectrometry coupled with our lab made protein database to identify LD-associated noncoding RNA-encoded proteins (LDANPs). A total of 15 new proteins were identified. One of them was studied further and termed LDANP1. LDANP1 was localized on LDs by imaging, cell fractionation, and immunogold labeling. Like LD resident proteins, LDANP1 was degraded by the proteasome. Using the CRISPR/Cas9-mediated genome editing technique, the endogenous expression of LDANP1 was validated. The stable expression of LDANP1 suppressed the accumulation of triacylglycerol in oleic acid treated myoblasts and inhibited the rescue of palmitate-inhibited insulin sensitivity by oleic acid. In summary, we report for the first time that translatable, nominally noncoding RNA-derived proteins, which are new and cannot be identified using current research methods, were associated with LDs and that among these, LDANP1 modulated lipid metabolism and insulin sensitivity. The discovery of noncoding RNA-encoded proteins on LDs paves a new way for the research of LDs and lipid metabolism.

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Stereochemistry of Astaxanthin Biosynthesis in the Marine Harpacticoid Copepod Tigriopus Californicus

Marine Drugs ◽

10.3390/md18100506 ◽

2020 ◽

Vol 18 (10) ◽

pp. 506

Author(s):

Alfonso Prado-Cabrero ◽

Ganjar Saefurahman ◽

John M. Nolan

Keyword(s):

High Performance ◽

Harpacticoid Copepod ◽

Model Organism ◽

Diode Array ◽

Hydroxyl Groups ◽

Tigriopus Californicus ◽

Nutritional Profile ◽

Array Detection ◽

First Time ◽

Feeding Sources

The harpacticoid copepod Tigriopus californicus has been recognized as a model organism for the study of marine pollutants. Furthermore, the nutritional profile of this copepod is of interest to the aquafeed industry. Part of this interest lies in the fact that Tigriopus produces astaxanthin, an essential carotenoid in salmonid aquaculture. Here, we study for the first time the stereochemistry of the astaxanthin produced by this copepod. We cultured T. californicus with different feeding sources and used chiral high-performance liquid chromatography with diode array detection (HPLC-DAD) to determine that T. californicus synthesizes pure 3S,3’S-astaxanthin. Using meso-zeaxanthin as feed, we found that the putative ketolase enzyme from T. californicus can work with β-rings with either 3R- or 3S-oriented hydroxyl groups. Despite this ability, experiments in the presence of hydroxylated and non-hydroxylated carotenoids suggest that T. californicus prefers to use the latter to produce 3S,3’S-astaxanthin. We suggest that the biochemical tools described in this work can be used to study the mechanistic aspects of the recently identified avian ketolase.

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