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Article ; Online: Development of a continuous assay for high throughput screening to identify inhibitors of the purine salvage pathway in Plasmodium falciparum

Christopher D. Grube / Cameron P. Gill / Hervé Roy

SLAS Discovery, Vol 27, Iss 2, Pp 114-

2022 Volume 120

Abstract: Malaria, an infectious disease caused by protozoan parasites from the genus Plasmodium, represents a serious global health threat. The continued emergence of drug resistant strains has severely decreased current antimalarial drug efficacy and led to a ... ...

Abstract	Malaria, an infectious disease caused by protozoan parasites from the genus Plasmodium, represents a serious global health threat. The continued emergence of drug resistant strains has severely decreased current antimalarial drug efficacy and led to a perpetual race for drug discovery. Most protozoan parasites, including Plasmodium spp., are unable to synthesize purines de novo and instead rely on an essential purine salvage pathway for acquisition of purines from the infected host. Because purines are essential for Plasmodium growth and survival, the enzymes of the purine salvage pathway represent promising targets for drug discovery. Target-based high-throughput screening (HTS) assays traditionally focus on a single target, which severely limits the screening power of this type of approach. To circumvent this limitation, we have reconstituted the purine salvage pathway from Plasmodium falciparum in an assay combining four drug targets. This assay was developed for HTS and optimized to detect partial inhibition of any of the four enzymes in the pathway. Inhibitors of several enzymes in the pathway were identified in a pilot screen, with several compounds exhibiting effective inhibition when provided in micromolar amounts.
Keywords	Purine salvage pathway ; Multiple targets ; High-throughput screening assay ; Pathway targeting ; Medicine (General) ; R5-920 ; Biotechnology ; TP248.13-248.65
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The MprF homolog LysX synthesizes lysyl-diacylglycerol contributing to antibiotic resistance and virulence.

Gill, Cameron P / Phan, Christopher / Platt, Vivien / Worrell, Danielle / Andl, Thomas / Roy, Hervé

Microbiology spectrum

2023 , Page(s) e0142923

Abstract: Lysyl-diacylglycerol (Lys-DAG) was identified three decades ago ... ...

Abstract	Lysyl-diacylglycerol (Lys-DAG) was identified three decades ago in
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01429-23
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Machine and deep learning approaches to understand and predict habitat suitability for seabird breeding

Antonio Garcia‐Quintas / Amédée Roy / Christophe Barbraud / Hervé Demarcq / Dennis Denis / Sophie Lanco Bertrand

Ecology and Evolution, Vol 13, Iss 9, Pp n/a-n/a (2023)

2023

Abstract: Abstract The way animals select their breeding habitat may have great impacts on individual fitness. This complex process depends on the integration of information on various environmental factors, over a wide range of spatiotemporal scales. For seabirds, ...

Abstract	Abstract The way animals select their breeding habitat may have great impacts on individual fitness. This complex process depends on the integration of information on various environmental factors, over a wide range of spatiotemporal scales. For seabirds, breeding habitat selection integrates both land and sea features over several spatial scales. Seabirds explore these features prior to breeding, assessing habitats' quality. However, the information‐gathering and decision‐making process by seabirds when choosing a breeding habitat remains poorly understood. We compiled 49 historical records of larids colonies in Cuba from 1980 to 2020. Then, we predicted potentially suitable breeding sites for larids and assessed their breeding macrohabitat selection, using deep and machine learning algorithms respectively. Using a convolutional neural network and Landsat satellite images we predicted the suitability for nesting of non‐monitored sites of this archipelago. Furthermore, we assessed the relative contribution of 18 land‐ and marine‐based environmental covariates describing macrohabitats at three spatial scales (i.e. 10, 50 and 100 km) using random forests. Convolutional neural network exhibited good performance at training, validation and test (F1‐scores >85%). Sites with higher habitat suitability (p > .75) covered 20.3% of the predicting area. Larids breeding macrohabitats were sites relatively close to main islands, featuring sparse vegetation cover and high chlorophyll‐a concentration at sea in 50 and 100 km around colonies. Lower sea surface temperature at larger spatial scales was determinant to distinguish the breeding from non‐breeding sites. A more comprehensive understanding of the seabird breeding macrohabitats selection can be reached from the complementary use of convolutional neural networks and random forest models. Our analysis provides crucial knowledge in tropical regions that lack complete and regular monitoring of seabirds' breeding sites.
Keywords	animal habitat modeling ; convolutional neural networks ; gulls and terns breeding ; remote sensing ; seabirds' colonies ; selection pattern ; Ecology ; QH540-549.5
Subject code	590
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article: Machine and deep learning approaches to understand and predict habitat suitability for seabird breeding.

Garcia-Quintas, Antonio / Roy, Amédée / Barbraud, Christophe / Demarcq, Hervé / Denis, Dennis / Lanco Bertrand, Sophie

Ecology and evolution

2023 Volume 13, Issue 9, Page(s) e10549

Abstract: The way animals select their breeding habitat may have great impacts on individual fitness. This complex process depends on the integration of information on various environmental factors, over a wide range of spatiotemporal scales. For seabirds, ... ...

Abstract	The way animals select their breeding habitat may have great impacts on individual fitness. This complex process depends on the integration of information on various environmental factors, over a wide range of spatiotemporal scales. For seabirds, breeding habitat selection integrates both land and sea features over several spatial scales. Seabirds explore these features prior to breeding, assessing habitats' quality. However, the information-gathering and decision-making process by seabirds when choosing a breeding habitat remains poorly understood. We compiled 49 historical records of larids colonies in Cuba from 1980 to 2020. Then, we predicted potentially suitable breeding sites for larids and assessed their breeding macrohabitat selection, using deep and machine learning algorithms respectively. Using a convolutional neural network and Landsat satellite images we predicted the suitability for nesting of non-monitored sites of this archipelago. Furthermore, we assessed the relative contribution of 18 land- and marine-based environmental covariates describing macrohabitats at three spatial scales (i.e. 10, 50 and 100 km) using random forests. Convolutional neural network exhibited good performance at training, validation and test (F1-scores >85%). Sites with higher habitat suitability (
Language	English
Publishing date	2023-09-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2635675-2
ISSN	2045-7758
ISSN	2045-7758
DOI	10.1002/ece3.10549
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Article ; Online: Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing in Trypanosoma and Leishmania.

Asencio, Corinne / Hervé, Perrine / Morand, Pauline / Oliveres, Quentin / Morel, Chloé Alexandra / Prouzet-Mauleon, Valérie / Biran, Marc / Monic, Sarah / Bonhivers, Mélanie / Robinson, Derrick Roy / Ouellette, Marc / Rivière, Loïc / Bringaud, Frédéric / Tetaud, Emmanuel

Molecular microbiology

2024

Abstract: Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease ( ... ...

Abstract	Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and various forms of leishmaniasis (Leishmania spp.), as well as several animal diseases with important economic impact (African trypanosomes, including Trypanosoma congolense). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinant Streptococcus pyogenes Cas9 (SpCas9) and an in vitro-synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete, and mutate candidate genes in various stages of the life cycle of T. brucei and T. congolense, and Leishmania promastigotes. The functionality of SpCas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics but requires only cloning and PCR screening of the clones. Importantly, this approach is adaptable to any wild-type parasite.
Language	English
Publishing date	2024-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/mmi.15256
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Jg. 1995 - 2021: Lesesall (2.OG)
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Article ; Online: Development of a continuous assay for high throughput screening to identify inhibitors of the purine salvage pathway in Plasmodium falciparum.

Grube, Christopher D / Gill, Cameron P / Roy, Hervé

SLAS discovery : advancing life sciences R & D

2021 Volume 27, Issue 2, Page(s) 114–120

Abstract	Malaria, an infectious disease caused by protozoan parasites from the genus Plasmodium, represents a serious global health threat. The continued emergence of drug resistant strains has severely decreased current antimalarial drug efficacy and led to a perpetual race for drug discovery. Most protozoan parasites, including Plasmodium spp., are unable to synthesize purines de novo and instead rely on an essential purine salvage pathway for acquisition of purines from the infected host. Because purines are essential for Plasmodium growth and survival, the enzymes of the purine salvage pathway represent promising targets for drug discovery. Target-based high-throughput screening (HTS) assays traditionally focus on a single target, which severely limits the screening power of this type of approach. To circumvent this limitation, we have reconstituted the purine salvage pathway from Plasmodium falciparum in an assay combining four drug targets. This assay was developed for HTS and optimized to detect partial inhibition of any of the four enzymes in the pathway. Inhibitors of several enzymes in the pathway were identified in a pilot screen, with several compounds exhibiting effective inhibition when provided in micromolar amounts.
MeSH term(s)	Antimalarials/pharmacology ; Drug Discovery ; High-Throughput Screening Assays ; Plasmodium falciparum ; Purines/metabolism ; Purines/pharmacology
Chemical Substances	Antimalarials ; Purines
Language	English
Publishing date	2021-12-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2885123-7
ISSN	2472-5560 ; 2472-5552
ISSN (online)	2472-5560
ISSN	2472-5552
DOI	10.1016/j.slasd.2021.12.002
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Zs.A 4911: Show issues

Location:
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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: A skin lesion hair mask dataset with fine-grained annotations.

Hossain, Sk Imran / Roy, Sudipta Singha / De Goër De Herve, Jocelyn / Mercer, Robert E / Mephu Nguifo, Engelbert

Data in brief

2023 Volume 48, Page(s) 109249

Abstract: Occlusion of skin lesions in dermoscopic images due to hair affects the performance of computer-assisted lesion analysis algorithms. Lesion analysis can benefit from digital hair removal or realistic hair simulation techniques. To assist in that process, ...

Abstract	Occlusion of skin lesions in dermoscopic images due to hair affects the performance of computer-assisted lesion analysis algorithms. Lesion analysis can benefit from digital hair removal or realistic hair simulation techniques. To assist in that process, we have created the largest publicly available skin lesion hair segmentation mask dataset by carefully annotating 500 dermoscopic images. Compared to the existing datasets, our dataset is free of non-hair artifacts like ruler markers, bubbles, and ink marks. The dataset is also less prone to over and under segmentations because of fine-grained annotations and quality checks from multiple independent annotators. To create the dataset, first, we collected five hundred copyright-free CC0 licensed dermoscopic images covering different hair patterns. Second, we trained a deep learning hair segmentation model on a publicly available weakly annotated dataset. Third, we extracted hair masks for the selected five hundred images using the segmentation model. Finally, we manually corrected all the segmentation errors and verified the annotations by superimposing the annotated masks on top of the dermoscopic images. Multiple annotators were involved in the annotation and verification process to make the annotations as error-free as possible. The prepared dataset will be useful for benchmarking and training hair segmentation algorithms as well as creating realistic hair augmentation systems.
Language	English
Publishing date	2023-05-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2023.109249
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Article: Using 18F-FDG-PET/CT Metrics to Predict Survival in Ra-Dio-Iodine Refractory Thyroid Cancers.

Roy, Malanie / Edet-Sanson, Agathe / Lefebvre, Hervé / Vera, Pierre / Decazes, Pierre

Diagnostics (Basel, Switzerland)

2022 Volume 12, Issue 10

Abstract: Radio-iodine refractory (RAI-R) differentiated thyroid cancer (DTC) is a rare disease with a poor prognosis and limited therapeutic resources. Therefore, identifying prognostic factors is essential in order to select patients who could benefit from an ... ...

Abstract	Radio-iodine refractory (RAI-R) differentiated thyroid cancer (DTC) is a rare disease with a poor prognosis and limited therapeutic resources. Therefore, identifying prognostic factors is essential in order to select patients who could benefit from an early start of treatment. The aim of this study is to identify positron emission tomography with 18F-fluorodeoxyglucose with integrated computed tomography (18F-FDG-PET/CT) parameters to predict overall survival (OS) in patients with RAI-R DTC. In this single-center retrospective study, we analyze the 18F-FDG-PET/CT parameters of 34 patients with RAI-R DTC between April 2007 and December 2019. The parameters collected are MTV, SUVmax and progression for each site of metastasis (neck, mediastinum, lungs, liver, bone) and total sites. ROC curves, Kaplan-Meier survival analysis curves, univariate and multivariate Cox analyses determine prognostic factors for 1-year and 5-year OS. The parameters for mediastinum, liver and total sites are significantly associated with worse 1-year and 5-year OS by both ROC curve analysis and Kaplan-Meier survival analysis. Univariate Cox analysis confirms significance of mediastinum SUVmax (HR 1.08; 95% CI [1.02-1.15];
Language	English
Publishing date	2022-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics12102381
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Article ; Online: Cohort profile

Julie Lopes / Clémence Baudin / Juliette Feuardent / Hervé Roy / Sylvaine Caër-Lorho / Klervi Leuraud / Marie-Odile Bernier

PLoS ONE, Vol 18, Iss

ORICAMs, a French cohort of medical workers exposed to low-dose ionizing radiation

2023 Volume 6

Abstract: Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in ... ...

Abstract	Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002–2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further ...
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2023-01-01T00:00:00Z
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: Cohort profile

Julie Lopes / Clémence Baudin / Juliette Feuardent / Hervé Roy / Sylvaine Caër-Lorho / Klervi Leuraud / Marie-Odile Bernier

PLoS ONE, Vol 18, Iss 6, p e

ORICAMs, a French cohort of medical workers exposed to low-dose ionizing radiation.

2023 Volume 0286910

Abstract	Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002-2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further ...
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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