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Article: Human metapneumovirus - what we know now.

Shafagati, Nazly / Williams, John

2018 Volume 7, Page(s) 135

Abstract: Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, ...

Abstract	Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response.
Keywords	covid19
Language	English
Publishing date	2018-02-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2699932-8
ISSN	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.12625.1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Human metapneumovirus - what we know now [version 1; referees

Nazly Shafagati / John Williams

F1000Research, Vol

2 approved]

2018 Volume 7

Abstract	Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response.
Keywords	Viral Infections (without HIV) ; Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	F1000 Research Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: CD4

Rogers, Meredith C / Lamens, Kristina D / Shafagati, Nazly / Johnson, Monika / Oury, Tim D / Joyce, Sebastian / Williams, John V

Journal of immunology (Baltimore, Md. : 1950)

2018 Volume 201, Issue 4, Page(s) 1253–1266

Abstract: Acute respiratory virus infection (ARI) induces ... ...

Abstract	Acute respiratory virus infection (ARI) induces CD8
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Female ; Influenza A Virus, H3N2 Subtype/immunology ; Male ; Metapneumovirus/immunology ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections/immunology ; Paramyxoviridae Infections/immunology ; T-Lymphocytes, Regulatory/immunology
Language	English
Publishing date	2018-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1800096
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Article ; Online: Enhanced detection of respiratory pathogens with nanotrap particles.

Shafagati, Nazly / Fite, Katherine / Patanarut, Alexis / Baer, Alan / Pinkham, Chelsea / An, Soyeon / Foote, Benjamin / Lepene, Benjamin / Kehn-Hall, Kylene

Virulence

2016 Volume 7, Issue 7, Page(s) 756–769

Abstract: The Influenza virus is a leading cause of respiratory disease in the United States each year. While the virus normally causes mild to moderate disease, hospitalization and death can occur in many cases. There are several methodologies that are used for ... ...

Abstract	The Influenza virus is a leading cause of respiratory disease in the United States each year. While the virus normally causes mild to moderate disease, hospitalization and death can occur in many cases. There are several methodologies that are used for detection; however problems such as decreased sensitivity and high rates of false-negative results may arise. There is a crucial need for an effective sample preparation technology that concentrates viruses at low abundance while excluding resident analytes that may interfere with detection. Nanotrap particles are hydrogel particles that are coupled to chemical dye affinity baits that bind a broad range of proteins and virions. Within minutes (<30 minutes), Nanotrap particles concentrate low abundant proteins and viruses from clinically complex matrices. Nanotrap particles with reactive red baits concentrated numerous respiratory viruses including various strains and subtypes of Influenza virus, Coronavirus, and Respiratory Syncytial Virus from saliva, nasal fluid swab specimens, and nasal aspirates. Detection was enhanced more than 10-fold when coupled to plaque assays and qRT-PCR. Importantly, Nanotrap particle can efficiently capture and concentrate multiple viral pathogens during a coinfection scenario. These results collectively demonstrate that Nanotrap particles are an important tool that can easily be integrated into various detection methodologies.
MeSH term(s)	Coinfection/virology ; Coronavirus/isolation & purification ; Coronavirus Infections/diagnosis ; Humans ; Influenza, Human/diagnosis ; Nanotechnology/methods ; Nose/virology ; Orthomyxoviridae/isolation & purification ; Respiratory Syncytial Viruses/isolation & purification ; Respiratory Tract Infections/diagnosis ; Respiratory Tract Infections/virology ; Saliva/virology
Keywords	covid19
Language	English
Publishing date	2016-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.1080/21505594.2016.1185585
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Article ; Online: The use of Nanotrap particles in the enhanced detection of Rift Valley fever virus nucleoprotein.

Shafagati, Nazly / Lundberg, Lindsay / Baer, Alan / Patanarut, Alexis / Fite, Katherine / Lepene, Benjamin / Kehn-Hall, Kylene

PloS one

2015 Volume 10, Issue 5, Page(s) e0128215

Abstract: Background: Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not ... ...

Abstract	Background: Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive enough to diagnose early infections. Furthermore, detection may be hindered by high abundant proteins such as albumin. Previous findings have shown that Nanotrap particles can be used to significantly enhance detection of various small analytes of low abundance. We have expanded upon this repertoire to show that this simple and efficient sample preparation technology can drastically improve the detection of the RVFV nucleoprotein (NP), the most abundant and widely used viral protein for RVFV diagnostics. Results: After screening multiple Nanotrap particle architectures, we found that one particle, NT45, was optimal for RVFV NP capture, as demonstrated by western blotting. NT45 significantly enhanced detection of the NP at levels undetectable without the technology. Importantly, we demonstrated that Nanotrap particles are capable of concentrating NP in a number of matrices, including infected cell lysates, viral supernatants, and animal sera. Specifically, NT45 enhanced detection of NP at various viral titers, multiplicity of infections, and time points. Our most dramatic results were observed in spiked serum samples, where high abundance serum proteins hindered detection of NP without Nanotrap particles. Nanotrap particles allowed for sample cleanup and subsequent detection of RVFV NP. Finally, we demonstrated that incubation of our samples with Nanotrap particles protects the NP from degradation over extended periods of time (up to 120 hours) and at elevated temperatures (at 37ºC). Conclusion: This study demonstrates that Nanotrap particles are capable of drastically lowering the limit of detection for RVFV NP by capturing, concentrating, and preserving RVFV NP in clinically relevant matrices. These studies can be extended to a wide range of pathogens and their analytes of diagnostic interest.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Humans ; Nanoparticles/chemistry ; Nanoparticles/metabolism ; Nucleoproteins/chemistry ; Nucleoproteins/metabolism ; Rift Valley Fever/diagnosis ; Rift Valley Fever/metabolism ; Rift Valley fever virus/chemistry ; Rift Valley fever virus/metabolism ; Vero Cells ; Viral Proteins/chemistry ; Viral Proteins/metabolism
Chemical Substances	Nucleoproteins ; Viral Proteins
Keywords	covid19
Language	English
Publishing date	2015-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0128215
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Article ; Online: The use of Nanotrap particles in the enhanced detection of Rift Valley fever virus nucleoprotein.

Nazly Shafagati / Lindsay Lundberg / Alan Baer / Alexis Patanarut / Katherine Fite / Benjamin Lepene / Kylene Kehn-Hall

PLoS ONE, Vol 10, Iss 5, p e

2015 Volume 0128215

Abstract: Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive ... ...

Abstract	Rift Valley fever virus (RVFV) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. While there are several diagnostic methodologies available for RVFV detection, many are not sensitive enough to diagnose early infections. Furthermore, detection may be hindered by high abundant proteins such as albumin. Previous findings have shown that Nanotrap particles can be used to significantly enhance detection of various small analytes of low abundance. We have expanded upon this repertoire to show that this simple and efficient sample preparation technology can drastically improve the detection of the RVFV nucleoprotein (NP), the most abundant and widely used viral protein for RVFV diagnostics.After screening multiple Nanotrap particle architectures, we found that one particle, NT45, was optimal for RVFV NP capture, as demonstrated by western blotting. NT45 significantly enhanced detection of the NP at levels undetectable without the technology. Importantly, we demonstrated that Nanotrap particles are capable of concentrating NP in a number of matrices, including infected cell lysates, viral supernatants, and animal sera. Specifically, NT45 enhanced detection of NP at various viral titers, multiplicity of infections, and time points. Our most dramatic results were observed in spiked serum samples, where high abundance serum proteins hindered detection of NP without Nanotrap particles. Nanotrap particles allowed for sample cleanup and subsequent detection of RVFV NP. Finally, we demonstrated that incubation of our samples with Nanotrap particles protects the NP from degradation over extended periods of time (up to 120 hours) and at elevated temperatures (at 37ºC).This study demonstrates that Nanotrap particles are capable of drastically lowering the limit of detection for RVFV NP by capturing, concentrating, and preserving RVFV NP in clinically relevant matrices. These studies can be extended to a wide range of pathogens and their analytes of diagnostic interest.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.

Lundberg, Lindsay / Pinkham, Chelsea / de la Fuente, Cynthia / Brahms, Ashwini / Shafagati, Nazly / Wagstaff, Kylie M / Jans, David A / Tamir, Sharon / Kehn-Hall, Kylene

PLoS neglected tropical diseases

2016 Volume 10, Issue 11, Page(s) e0005122

Abstract: The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT- ... ...

Abstract	The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible. Chemically inhibiting CRM1 with these compounds enhanced capsid localization to the nucleus compared to the inactive compound KPT-301, as indicated by immunofluorescent confocal microscopy. Differences in extracellular versus intracellular viral RNA, as well as decreased capsid in cell free supernatants, indicated the inhibitors affected viral assembly, which led to a decrease in viral titers. The decrease in viral replication was confirmed using a luciferase-tagged virus and through plaque assays. SINE compounds had no effect on VEEV TC83_Cm, which encodes a mutated form of capsid that is unable to enter the nucleus. Serially passaging VEEV in the presence of KPT-185 resulted in mutations within the nuclear localization and nuclear export signals of capsid. Finally, SINE compound treatment also reduced the viral titers of the related eastern and western equine encephalitis viruses, suggesting that CRM1 maintains a common interaction with capsid proteins across the New World alphavirus genus.
MeSH term(s)	Active Transport, Cell Nucleus/drug effects ; Alphavirus/drug effects ; Alphavirus/genetics ; Alphavirus/physiology ; Alphavirus Infections/virology ; Animals ; Antiviral Agents/pharmacology ; Capsid Proteins/genetics ; Capsid Proteins/metabolism ; Cell Nucleus/virology ; Humans ; Karyopherins/antagonists & inhibitors ; Karyopherins/genetics ; Karyopherins/metabolism ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Virus Assembly/drug effects ; Virus Replication/drug effects ; Exportin 1 Protein
Chemical Substances	Antiviral Agents ; Capsid Proteins ; Karyopherins ; Receptors, Cytoplasmic and Nuclear
Language	English
Publishing date	2016-11-30
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0005122
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Protein Phosphatase-1 regulates Rift Valley fever virus replication.

Baer, Alan / Shafagati, Nazly / Benedict, Ashwini / Ammosova, Tatiana / Ivanov, Andrey / Hakami, Ramin M / Terasaki, Kaori / Makino, Shinji / Nekhai, Sergei / Kehn-Hall, Kylene

Antiviral research

2016 Volume 127, Page(s) 79–89

Abstract: Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both ... ...

Abstract	Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a significant role in the replication of several viruses. Here we demonstrate for the first time that PP1 plays a prominent role in RVFV replication early on during the viral life cycle. Both siRNA knockdown of PP1α and a novel PP1-targeting small molecule compound 1E7-03, resulted in decreased viral titers across several cell lines. Deregulation of PP1 was found to inhibit viral RNA production, potentially through the disruption of viral RNA transcript/protein interactions, and indicates a potential link between PP1α and the viral L polymerase and nucleoprotein. These results indicate that PP1 activity is important for RVFV replication early on during the viral life cycle and may prove an attractive therapeutic target.
MeSH term(s)	Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Cell Line ; DNA Replication/drug effects ; DNA Replication/physiology ; Genome, Viral/drug effects ; Host-Pathogen Interactions ; Humans ; Indoles/pharmacology ; Phosphorylation/drug effects ; Protein Binding/drug effects ; Protein Phosphatase 1/antagonists & inhibitors ; Protein Phosphatase 1/metabolism ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/genetics ; RNA, Viral/biosynthesis ; RNA, Viral/drug effects ; Rift Valley Fever/drug therapy ; Rift Valley Fever/virology ; Rift Valley fever virus/drug effects ; Rift Valley fever virus/enzymology ; Rift Valley fever virus/genetics ; Rift Valley fever virus/physiology ; Urea/analogs & derivatives ; Urea/pharmacology ; Vero Cells ; Viral Proteins/antagonists & inhibitors ; Viral Proteins/metabolism ; Virulence ; Virus Replication/drug effects ; Virus Replication/physiology
Chemical Substances	1E7-03 compound ; Antiviral Agents ; Indoles ; RNA, Small Interfering ; RNA, Viral ; Viral Proteins ; Urea (8W8T17847W) ; Protein Phosphatase 1 (EC 3.1.3.16)
Language	English
Publishing date	2016-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2016.01.007
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Article ; Online: The use of NanoTrap particles as a sample enrichment method to enhance the detection of Rift Valley Fever Virus.

Shafagati, Nazly / Narayanan, Aarthi / Baer, Alan / Fite, Katherine / Pinkham, Chelsea / Bailey, Charles / Kashanchi, Fatah / Lepene, Benjamin / Kehn-Hall, Kylene

PLoS neglected tropical diseases

2013 Volume 7, Issue 7, Page(s) e2296

Abstract: Background: Rift Valley Fever Virus (RVFV) is a zoonotic virus that is not only an emerging pathogen but is also considered a biodefense pathogen due to the threat it may cause to public health and national security. The current state of diagnosis has ... ...

Abstract	Background: Rift Valley Fever Virus (RVFV) is a zoonotic virus that is not only an emerging pathogen but is also considered a biodefense pathogen due to the threat it may cause to public health and national security. The current state of diagnosis has led to misdiagnosis early on in infection. Here we describe the use of a novel sample preparation technology, NanoTrap particles, to enhance the detection of RVFV. Previous studies demonstrated that NanoTrap particles lead to both 100 percent capture of protein analytes as well as an improvement of more than 100-fold in sensitivity compared to existing methods. Here we extend these findings by demonstrating the capture and enrichment of viruses. Results: Screening of NanoTrap particles indicated that one particle, NT53, was the most efficient at RVFV capture as demonstrated by both qRT-PCR and plaque assays. Importantly, NT53 capture of RVFV resulted in greater than 100-fold enrichment from low viral titers when other diagnostics assays may produce false negatives. NT53 was also capable of capturing and enhancing RVFV detection from serum samples. RVFV that was inactivated through either detergent or heat treatment was still found bound to NT53, indicating the ability to use NanoTrap particles for viral capture prior to transport to a BSL-2 environment. Furthermore, both NP-40-lysed virus and purified RVFV RNA were bound by NT53. Importantly, NT53 protected viral RNA from RNase A degradation, which was not observed with other commercially available beads. Incubation of RVFV samples with NT53 also resulted in increased viral stability as demonstrated through preservation of infectivity at elevated temperatures. Finally, NanoTrap particles were capable of capturing VEEV and HIV, demonstrating the broad applicability of NanoTrap particles for viral diagnostics. Conclusion: This study demonstrates NanoTrap particles are capable of capturing, enriching, and protecting RVFV virions. Furthermore, the use of NanoTrap particles can be extended to a variety of viruses, including VEEV and HIV.
MeSH term(s)	Animals ; Humans ; Nanoparticles/virology ; RNA, Viral/isolation & purification ; Rift Valley Fever/virology ; Rift Valley fever virus/isolation & purification ; Serum/virology ; Specimen Handling/methods ; Virology/methods
Chemical Substances	RNA, Viral
Keywords	covid19
Language	English
Publishing date	2013-07-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2727
ISSN (online)	1935-2735
ISSN	1935-2727
DOI	10.1371/journal.pntd.0002296
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Selective Inhibitor of Nuclear Export (SINE) Compounds Alter New World Alphavirus Capsid Localization and Reduce Viral Replication in Mammalian Cells.

Lindsay Lundberg / Chelsea Pinkham / Cynthia de la Fuente / Ashwini Brahms / Nazly Shafagati / Kylie M Wagstaff / David A Jans / Sharon Tamir / Kylene Kehn-Hall

PLoS Neglected Tropical Diseases, Vol 10, Iss 11, p e

2016 Volume 0005122

Abstract	The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible. Chemically inhibiting CRM1 with these compounds enhanced capsid localization to the nucleus compared to the inactive compound KPT-301, as indicated by immunofluorescent confocal microscopy. Differences in extracellular versus intracellular viral RNA, as well as decreased capsid in cell free supernatants, indicated the inhibitors affected viral assembly, which led to a decrease in viral titers. The decrease in viral replication was confirmed using a luciferase-tagged virus and through plaque assays. SINE compounds had no effect on VEEV TC83_Cm, which encodes a mutated form of capsid that is unable to enter the nucleus. Serially passaging VEEV in the presence of KPT-185 resulted in mutations within the nuclear localization and nuclear export signals of capsid. Finally, SINE compound treatment also reduced the viral titers of the related eastern and western equine encephalitis viruses, suggesting that CRM1 maintains a common interaction with capsid proteins across the New World alphavirus genus.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	570
Language	English
Publishing date	2016-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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