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Article ; Online: HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

Fengwen Zhang / Paul D Bieniasz

eLife, Vol

2020 Volume 9

Abstract: The HIV-1 Vpr accessory protein induces ubiquitin/proteasome-dependent degradation of many cellular proteins by recruiting them to a cullin4A-DDB1-DCAF1 complex. In so doing, Vpr enhances HIV-1 gene expression and induces (G2/M) cell cycle arrest. ... ...

Abstract	The HIV-1 Vpr accessory protein induces ubiquitin/proteasome-dependent degradation of many cellular proteins by recruiting them to a cullin4A-DDB1-DCAF1 complex. In so doing, Vpr enhances HIV-1 gene expression and induces (G2/M) cell cycle arrest. However, the identities of Vpr target proteins through which these biological effects are exerted are unknown. We show that a chromosome periphery protein, CCDC137/cPERP-B, is targeted for depletion by HIV-1 Vpr, in a cullin4A-DDB1-DCAF1 dependent manner. CCDC137 depletion caused G2/M cellcycle arrest, while Vpr-resistant CCDC137 mutants conferred resistance to Vpr-induced G2/M arrest. CCDC137 depletion also recapitulated the ability of Vpr to enhance HIV-1 gene expression, particularly in macrophages. Our findings indicate that Vpr promotes cell-cycle arrest and HIV-1 gene expression through depletion of CCDC137.
Keywords	HIV-1 ; Vpr ; CCDC137 ; macrophages ; cd4+ t-ell ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Method validation and dissipation kinetics of the novel HPPD-inhibiting herbicide cypyrafluone in winter wheat using QuEChERS method coupled with UPLC-MS/MS

Cheng Yang / Fengwen Zhang / Yunxia Duan / Xingtao Lu / Xuegang Peng / Jinxin Wang / Lang Pan / Weitang Liu / Hengzhi Wang

Ecotoxicology and Environmental Safety, Vol 260, Iss , Pp 115090- (2023)

2023

Abstract: Cypyrafluone, a novel hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide, can successfully control a wide species of grass and broadleaf weed in wheat fields. However, the dissipation behaviors and terminal residues of cypyrafluone in wheat ... ...

Abstract	Cypyrafluone, a novel hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide, can successfully control a wide species of grass and broadleaf weed in wheat fields. However, the dissipation behaviors and terminal residues of cypyrafluone in wheat fields remain unclear. Here, a simple, accurate, and dependable approach for the analysis of cypyrafluone in soil, wheat plant, and grain was constructed utilizing an adapted QuEChERS extraction combined with UPLC-MS/MS. For accurate quantification, matrix-matched calibrations with high linearity (R2 >0.99) were employed to eliminate matrix interference. The method possessed high accuracy with recoveries in the range of 85.5%− 100.6% and precision with relative standard deviations < 14.3%, as well as high sensitivity with limits of quantifications of 0.001 mg kg−1 in the three matrixes. The dissipation kinetics and terminal residues of cypyrafluone were determined at two separate locations with different climates, soil types and cropping systems in 2018. The half-lives of cypyrafluone in soil and wheat plant were 1.47–1.55 d and 1.00–1.03 d, respectively. At harvest, the terminal residue values of cypyrafluone detected in wheat plants were 0–0.0025 mg kg−1 and 0.0044–0.0057 mg kg−1 at the recommended dose and 1.5 times of the recommended dose, respectively, and 0.0049 mg kg−1 of this herbicide was detected in grain at 1.5 times of the recommended dose, which was below the maximum residue limit (MRL). Finally, the risk quotient for cypyrafluone ranged from 0.33% to 0.81% (<1) for different age groups in China, indicating that the impact of residues from the cypyrafluone application on wheat was acceptable. These findings above will offer scientific guidelines for cypyrafluone application in the wheat field ecosystem.
Keywords	HPPD inhibitor ; QYM201 ; Dissipation ; Wheat ; Dietary risk assessment ; Environmental pollution ; TD172-193.5 ; Environmental sciences ; GE1-350
Subject code	571
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Biodegradable Cardiac Occluder with Surface Modification by Gelatin–Peptide Conjugate to Promote Endogenous Tissue Regeneration

Pengxu Kong / Xiang Liu / Zefu Li / Jingrong Wang / Rui Gao / Shuyi Feng / Hang Li / Fengwen Zhang / Zujian Feng / Pingsheng Huang / Shouzheng Wang / Donglin Zhuang / Wenbin Ouyang / Weiwei Wang / Xiangbin Pan

Advanced Science, Vol 11, Iss 2, Pp n/a-n/a (2024)

2024

Abstract: Abstract Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for ...

Abstract	Abstract Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long‐term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l‐lactic acid)–gelatin–A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein‐derived peptides (A5G81) to the surface of polydioxanone and poly (l‐lactic acid) fibers. The polymer microfiber–biomacromolecule–peptide frame with biophysical and biochemical cues could orchestrate the biomaterial–host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti‐inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell–biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell–material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.
Keywords	biodegradable polymers ; cell–material interface ; congenital heart disease ; occluder ; tissue regeneration ; Science ; Q
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Direct toxicity of the herbicide florasulam against Chlorella vulgaris

Qin Jiao / Yuelin Mu / Jiahui Deng / Xiangfeng Yao / Xiaoyan Zhao / Xiang Liu / Xiangdong Li / Xingyin Jiang / Fengwen Zhang

Ecotoxicology and Environmental Safety, Vol 246, Iss , Pp 114135- (2022)

An integrated physiological and metabolomic analysis

2022

Abstract: Herbicides are the agents of choice for use in weed control; however, they can enter the aquatic environment, with potentially serious consequences for non-target organisms. Despite the possible deleterious effects, little information is available ... ...

Abstract	Herbicides are the agents of choice for use in weed control; however, they can enter the aquatic environment, with potentially serious consequences for non-target organisms. Despite the possible deleterious effects, little information is available regarding the ecotoxicity of the herbicide florasulam toward aquatic organisms. Accordingly, in this study, we investigated the toxic effect of florasulam on the freshwater microalga Chlorella vulgaris and sought to identify the underlying mechanisms. For this, we employed a growth inhibition toxicity test, and then assessed the changes in physiological and metabolomic parameters, including photosynthetic pigment content, antioxidant system, intracellular structure and complexity, and metabolite levels. The results showed that treatment with florasulam for 96 h at the concentration of 2 mg/L, 2.84 mg/L, and 6 mg/L in medium significantly inhibited algal growth and photosynthetic pigment content. Moreover, the levels of reactive oxygen species were also increased, resulting in oxidative damage and the upregulation of the activities of several antioxidant enzymes. Transmission electron microscopic and flow cytometric analysis further demonstrated that exposure to florasulam (6 mg/L) for 96 h disrupted the cell structure of C. vulgaris, characterized by the loss of cell membrane integrity and alterations in cell morphology. Changes in amino acid metabolism, carbohydrate metabolism, and the antioxidant system were also observed and contributed to the suppressive effect of florasulam on the growth of this microalga. Our findings regarding the potential risks of florasulam in aquatic ecosystems provide a reference for the safe application of this herbicide in the environment.
Keywords	Florasulam ; C. vulgaris ; Growth ; Oxidative stress ; Metabolomics ; Environmental pollution ; TD172-193.5 ; Environmental sciences ; GE1-350
Subject code	500
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Greenhouse and field evaluation of a novel HPPD-inhibiting herbicide, QYM201, for weed control in wheat

Fengwen Zhang / Shuang Bai / Hengzhi Wang / Weitang Liu / Jinxin Wang

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 9

Abstract: Abstract QYM201, 1-(2-chloro-3-(3-cyclopropyl-5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-6-(trifluoromethyl)phenyl)piperidin-2-one), is a newly developed HPPD- (4-hydroxyphenylpyruvate dioxygenase; EC 1.13.11.27) inhibiting herbicide for weed control. ... ...

Abstract	Abstract QYM201, 1-(2-chloro-3-(3-cyclopropyl-5-hydroxy-1-methyl-1H-pyrazole-4-carbonyl)-6-(trifluoromethyl)phenyl)piperidin-2-one), is a newly developed HPPD- (4-hydroxyphenylpyruvate dioxygenase; EC 1.13.11.27) inhibiting herbicide for weed control. Experiments were carried out to determine the effect of QYM201 on weeds and its safety for wheat in the glasshouse and field. The results indicated that at doses of 90 and 135 g active ingredient (a.i.) ha−1 QYM201 was highly effective against both grass and broadleaf weeds, such as Alopecurus aequalis Sobol., Alopecurus japonicus Steud, and Capsella bursa-pastoris Medic. In a wheat hybrid tolerance experiment, QYM201 showed a high level of safety for most of the 17 tested wheat hybrids, and the SI values reached ≥5.7 in the selectivity index study. To determine application rules for QYM201, field experiments were conducted in 2016 and 2017. During this time, 90 to 270 g a.i. ha−1 post-emergence herbicide application (POST) was sufficient to supply satisfactory all-season control of Alopecurus aequalis Sobol., Descurainia sophia [L.] Schur., and Malachium aquaticum (L.) Fires. No damage to wheat plants was observed. In order to increase wheat yield and deliver effective weed control, a dosage of 90 to 180 g a.i. ha−1 is suggested. In conclusion, the herbicide QYM201 is safe to use in wheat fields to control winter weeds.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transcriptomics and enzymology combined five gene expressions to reveal the responses of earthworms (Eisenia fetida) to the long-term exposure of cyantraniliprole in soil

Zhihua Qiao / Xiangfeng Yao / Xiang Liu / Jianye Zhang / Qingzhi Du / Fengwen Zhang / Xiangdong Li / Xingyin Jiang

Ecotoxicology and Environmental Safety, Vol 209, Iss , Pp 111824- (2021)

2021

Abstract: Cyantraniliprole is a novel diamide insecticide that acts upon the ryanodine receptor (RyR) and has broad application prospects. Accordingly, it is very important to evaluate the toxicity of cyantraniliprole to earthworms (Eisenia fetida) because of ... ...

Abstract	Cyantraniliprole is a novel diamide insecticide that acts upon the ryanodine receptor (RyR) and has broad application prospects. Accordingly, it is very important to evaluate the toxicity of cyantraniliprole to earthworms (Eisenia fetida) because of their vital role in maintaining a healthy soil ecosystem. In this study, an experiment was set up, using four concentrations (0.1, 1, 5, and 10 mg/kg) and solvent control group (0 mg/kg), to investigate the ecotoxicity of cyantraniliprole to earthworms. Our results showed that, after 28 days of exposure to cyantraniliprole, both cocoon production and the number of juvenile earthworms had decreased significantly at concentrations of either 5 or 10 mg/kg. On day 14, we measured the activities of digestive enzymes and ion pumps in the intestinal tissues of earthworms. These results revealed that cyantraniliprole exposure caused intestinal damage in earthworm, specifically changes to its intestinal enzyme activity and calcium ion content. Cyantraniliprole could lead to proteins’ carbonylation under the high-dose treatments (i.e., 5 mg/kg, 10 mg/kg). At the same time, we also found that cyantraniliprole can cause the abnormal expression of key functional genes (including HSP70, CAT, RYR, ANN, and CAM genes). Moreover, the transcriptomics data showed that exposure to cyantraniliprole would affect the synthesis of carbohydrates, proteins and lipids, as well as their absorption and transformation, while cyantraniliprole would also affect signal transduction. In general, high-dose exposure to cyantraniliprole causes reproductive toxicity, genotoxicity, and intestinal damage to earthworms.
Keywords	Cyantraniliprole ; Earthworms ; Reproductive toxicity ; Genotoxicity ; Transcriptomics ; Environmental pollution ; TD172-193.5 ; Environmental sciences ; GE1-350
Subject code	333 ; 610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Single-Cell and Single-Cycle Analysis of HIV-1 Replication.

Mowgli Holmes / Fengwen Zhang / Paul D Bieniasz

PLoS Pathogens, Vol 11, Iss 6, p e

2015 Volume 1004961

Abstract: The dynamics of the late stages of the HIV-1 life cycle are poorly documented. Viral replication dynamics are typically measured in populations of infected cells, but asynchrony that is introduced during the early steps of HIV-1 replication complicates ... ...

Abstract	The dynamics of the late stages of the HIV-1 life cycle are poorly documented. Viral replication dynamics are typically measured in populations of infected cells, but asynchrony that is introduced during the early steps of HIV-1 replication complicates the measurement of the progression of subsequent steps and can mask replication dynamics and their variation in individual infected cells. We established microscopy-based methods to dynamically measure HIV-1-encoded reporter gene and antiviral gene expression in individual infected cells. We coupled these measurements with conventional analyses to quantify delays in the HIV-1 replication cycle imposed by the biphasic nature of HIV-1 gene expression and by the assembly-inhibiting property of the matrix domain of Gag. We further related the dynamics of restriction factor (APOBEC3G) removal to the dynamics of HIV-1 replication in individual cells. These studies provide a timeline for key events in the HIV-1 replication cycle, and reveal that the interval between the onset of early and late HIV-1 gene expression is only ~3 h, but matrix causes a ~6-12 h delay in the generation of extracellular virions. Interestingly, matrix delays particle assembly to a time at which APOBEC3G has largely been removed from the cell. Thus, a need to prepare infected cells to be efficient producers of infectious HIV-1 may provide an impetus for programmed delays in HIV-1 virion genesis. Our findings also emphasize the significant heterogeneity in the length of the HIV-1 replication cycle in homogenous cell populations and suggest that a typical infected cell generates new virions for only a few hours at the end of a 48 h lifespan. Therefore, small changes in the lifespan of infected cells might have a large effect on viral yield in a single cycle and the overall clinical course in infected individuals.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2015-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Hydration, water distribution and microstructure of gluten during freeze thaw process: Role of a high molecular weight dextran produced by Weissella confusa QS813

Tang, Xiaojuan / Binle Zhang / Feng Wang / Fengwen Zhang / Jianxian Zheng / Qibo Zou / Weining Huang / Zilin Ma

Food hydrocolloids. 2019 May, v. 90

2019

Abstract: The effect of exopolysaccharide (EPS) produced by Weissella confusa QS813 on the hydration, water distribution, rheology and microstructure of wheat gluten during freeze–thaw cycles (FTC) was investigated. Addition of EPS increased the water content of ... ...

Abstract	The effect of exopolysaccharide (EPS) produced by Weissella confusa QS813 on the hydration, water distribution, rheology and microstructure of wheat gluten during freeze–thaw cycles (FTC) was investigated. Addition of EPS increased the water content of fresh gluten and delayed the dehydration of gluten during FTC. Low field-nuclear magnetic resonance showed that the presence of EPS reduced the mobility of both confined and bulk water in the fresh gluten matrix. Proton distribution changes in gluten during FTC indicated that deterioration of the gluten network was attributable to ice recrystallization of capillary confined water and bulk water. The presence of EPS effectively reduced the release of bulk water and retarded the redistribution of confined water induced by FTC. Dynamic oscillatory studies indicated that the presence of EPS induced a softening effect on the fresh gluten. FTC significantly decreased the rheological parameters, storage modulus (G′) and loss modulus (G′′), of all gluten samples. Gluten with higher concentrations of EPS (above 0.5%) exhibited a delayed decrease in G′ and G′′ and maintained a constant tanδ value after FTC. Laser scanning confocal microscope and scanning electron microscope revealed that EPS maintained the structural integrity of gluten during FTC, suggesting an inhibitory effect on the recrystallization of ice crystals. These results in the present study indicated that the bacterial dextran is a promising cryoprotectant for the frozen dough industry.
Keywords	cryoprotectants ; crystallization ; crystals ; dextran ; exopolysaccharides ; freeze-thaw cycles ; frozen dough ; hydrocolloids ; ice ; industry ; loss modulus ; magnetism ; microstructure ; molecular weight ; rheology ; scanning electron microscopes ; storage modulus ; water content ; water distribution ; Weissella confusa ; wheat gluten
Language	English
Dates of publication	2019-05
Size	p. 377-384.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	742742-6
ISSN	1873-7137 ; 0268-005X
ISSN (online)	1873-7137
ISSN	0268-005X
DOI	10.1016/j.foodhyd.2018.10.025
Database	NAL-Catalogue (AGRICOLA)

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Article: Target-site and non-target-site-based resistance to tribenuron-methyl in multiply-resistant Myosoton aquaticum L

Bai, Shuang / Fengwen Zhang / Hengzhi Wang / Jinxin Wang / Lianyang Bai / Qian Wang / Weitang Liu / Zuren Li

Pesticide biochemistry and physiology. 2019 Mar., v. 155

2019

Abstract: Myosoton aquaticum L., a widespread and competitive winter weed of wheat in China, has evolved resistance to many classes of herbicides. In one M. aquaticum population (AH03), collected from Anhui Province, where tribenuron-methyl and florasulam had been ...

Abstract	Myosoton aquaticum L., a widespread and competitive winter weed of wheat in China, has evolved resistance to many classes of herbicides. In one M. aquaticum population (AH03), collected from Anhui Province, where tribenuron-methyl and florasulam had been used to control this weed resistance to both herbicides had evolved. Compared with the sensitive population, HN03(S), the resistant (R) population, AH03, was highly resistant to tribenuron-methyl, flucarbazone-Na and pyroxsulam, moderately resistant to pyrithiobac‐sodium, and florasulam, and had low resistance to diflufenican. AH03 was still controlled by imazethapyr, 2,4-D butylate, fluroxypyr-meptyl, and isoproturon. Pretreatment with the P450 inhibitor malathion reduced the GR50 value of tribenuron-methyl by 43% in the R population, and by 25% in the S population. This indicates that P450-mediated enhanced metabolism is one likely mechanism for tribenuron-methyl resistance in M. aquaticum. Glutathione-S-transferase (GST) activity could be induced by tribenuron-methyl in both the R and S populations. However, both the basal and induced GST activity of the R population was lower than that of the S population. The in vitro ALS assay confirmed that the ALS from the R plants showed a high resistance (52.93-fold) to tribenuron-methyl. ALS gene sequencing revealed a Pro197Ala substitution in the R plants. Based on the ALS gene sequence analysis, molecular markers were also developed to identify the specific Pro197Ala mutation. This population of M. aquaticum has multiple resistance and target-site (ALS Pro197Ala) and non-target-site resistance mechanisms contribute to tribenuron-methyl resistance.
Keywords	2,4-D ; butylate ; diflufenican ; florasulam ; genetic markers ; glutathione transferase ; imazethapyr ; isoproturon ; malathion ; metabolism ; mutation ; Myosoton aquaticum ; resistance mechanisms ; sequence analysis ; weed control ; weeds ; wheat ; winter ; China
Language	English
Dates of publication	2019-03
Size	p. 8-14.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	184819-7
ISSN	1095-9939 ; 0048-3583 ; 0048-3575
ISSN (online)	1095-9939
ISSN	0048-3583 ; 0048-3575
DOI	10.1016/j.pestbp.2018.12.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Clathrin facilitates the morphogenesis of retrovirus particles.

Fengwen Zhang / Trinity Zang / Sam J Wilson / Marc C Johnson / Paul D Bieniasz

PLoS Pathogens, Vol 7, Iss 6, p e

2011 Volume 1002119

Abstract: The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in ... ...

Abstract	The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. One such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. We found that clathrin is not only exceptionally abundant in highly purified HIV-1 particles but is recruited with high specificity. In particular, the HIV-1 Pol protein was absolutely required for clathrin incorporation and point mutations in reverse transcriptase or integrase domains of Pol could abolish incorporation. Clathrin was also specifically incorporated into other retrovirus particles, including members of the lentivirus (simian immunodeficiency virus, SIVmac), gammaretrovirus (murine leukemia virus, MLV) and betaretrovirus (Mason-Pfizer monkey virus, M-PMV) genera. However, unlike HIV-1, these other retroviruses recruited clathrin primarily using peptide motifs in their respective Gag proteins that mimicked motifs found in cellular clathrin adaptors. Perturbation of clathrin incorporation into these retroviruses, via mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein (AP180) induced clathrin sequestration, had a range of effects on the accuracy of particle morphogenesis. These effects varied according to which retrovirus was examined, and included Gag and/or Pol protein destabilization, inhibition of particle assembly and reduction in virion infectivity. For each retrovirus examined, clathrin incorporation appeared to be important for optimal replication. These data indicate that a number of retroviruses employ clathrin to facilitate the accurate morphogenesis of infectious particles. We propose a model in which clathrin contributes to the spatial organization of Gag and Pol ...
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2011-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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