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Article ; Online: The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome.

Krischuns, Tim / Arragain, Benoît / Isel, Catherine / Paisant, Sylvain / Budt, Matthias / Wolff, Thorsten / Cusack, Stephen / Naffakh, Nadia

Nature communications

2024 Volume 15, Issue 1, Page(s) 1064

Abstract: ... in vitro approaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol ... to a replicase conformation in the presence of the bound RNPAII C-terminal domain and propose a model ...

Abstract	The current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we provide evidence that the FluPol-RNAP II binding interface, beyond its well-acknowledged function in cap-snatching during transcription initiation, has also a pivotal role in replication of the viral genome. Using a combination of cell-based and in vitro approaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol replication activity. We observe successive conformational changes to switch from a transcriptase to a replicase conformation in the presence of the bound RNPAII C-terminal domain and propose a model in which the host RNAP II is the anchor for transcription and replication of the viral genome. Our data open new perspectives on the spatial coupling of viral transcription and replication and the coordinated balance between these two activities.
MeSH term(s)	RNA Polymerase II/metabolism ; RNA-Dependent RNA Polymerase/metabolism ; RNA, Viral/genetics ; Orthomyxoviridae/genetics ; DNA-Directed RNA Polymerases ; Virus Replication/genetics
Chemical Substances	RNA Polymerase II (EC 2.7.7.-) ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; RNA, Viral ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
Language	English
Publishing date	2024-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45205-2
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Article ; Online: The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication.

Dupont, Maud / Krischuns, Tim / Gianetto, Quentin Giai / Paisant, Sylvain / Bonazza, Stefano / Brault, Jean-Baptiste / Douché, Thibaut / Arragain, Benoît / Florez-Prada, Alberto / Perez-Perri, Joel I / Hentze, Matthias W / Cusack, Stephen / Matondo, Mariette / Isel, Catherine / Courtney, David G / Naffakh, Nadia

Nucleic acids research

2024

Abstract: ... polymerase recruits TDP-43 onto viral mRNAs through a direct interaction with the disordered C-terminal ...

Abstract	Genome-wide approaches have significantly advanced our knowledge of the repertoire of RNA-binding proteins (RBPs) that associate with cellular polyadenylated mRNAs within eukaryotic cells. Recent studies focusing on the RBP interactomes of viral mRNAs, notably SARS-Cov-2, have revealed both similarities and differences between the RBP profiles of viral and cellular mRNAs. However, the RBPome of influenza virus mRNAs remains unexplored. Herein, we identify RBPs that associate with the viral mRNA encoding the nucleoprotein (NP) of an influenza A virus. Focusing on TDP-43, we show that it binds several influenza mRNAs beyond the NP-mRNA, and that its depletion results in lower levels of viral mRNAs and proteins within infected cells, and a decreased yield of infectious viral particles. We provide evidence that the viral polymerase recruits TDP-43 onto viral mRNAs through a direct interaction with the disordered C-terminal domain of TDP-43. Notably, other RBPs found to be associated with influenza virus mRNAs also interact with the viral polymerase, which points to a role of the polymerase in orchestrating the assembly of viral messenger ribonucleoproteins.
Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Journal Article
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkae291
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Zs.A 1067: Show issues

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Article: Clinical performance and health equity implications of the American Diabetes Association's 2023 screening recommendation for prediabetes and diabetes.

O'Brien, Matthew J / Zhang, Yan / Bailey, Stacy C / Khan, Sadiya S / Ackermann, Ronald T / Ali, Mohammed K / Bowen, Michael E / Benoit, Stephen R / Imperatore, Giuseppina / Holliday, Christopher S / McKeever Bullard, Kai

Frontiers in endocrinology

2023 Volume 14, Page(s) 1279348

Abstract: Introduction: The American Diabetes Association (ADA) recommends screening for prediabetes and diabetes (dysglycemia) starting at age 35, or younger than 35 years among adults with overweight or obesity and other risk factors. Diabetes risk differs by ... ...

Abstract	Introduction: The American Diabetes Association (ADA) recommends screening for prediabetes and diabetes (dysglycemia) starting at age 35, or younger than 35 years among adults with overweight or obesity and other risk factors. Diabetes risk differs by sex, race, and ethnicity, but performance of the recommendation in these sociodemographic subgroups is unknown. Methods: Nationally representative data from the National Health and Nutrition Examination Surveys (2015-March 2020) were analyzed from 5,287 nonpregnant US adults without diagnosed diabetes. Screening eligibility was based on age, measured body mass index, and the presence of diabetes risk factors. Dysglycemia was defined by fasting plasma glucose ≥100mg/dL (≥5.6 mmol/L) or haemoglobin A1c ≥5.7% (≥39mmol/mol). The sensitivity, specificity, and predictive values of the ADA screening criteria were examined by sex, race, and ethnicity. Results: An estimated 83.1% (95% CI=81.2-84.7) of US adults were eligible for screening according to the 2023 ADA recommendation. Overall, ADA's screening criteria exhibited high sensitivity [95.0% (95% CI=92.7-96.6)] and low specificity [27.1% (95% CI=24.5-29.9)], which did not differ by race or ethnicity. Sensitivity was higher among women [97.8% (95% CI=96.6-98.6)] than men [92.4% (95% CI=88.3-95.1)]. Racial and ethnic differences in sensitivity and specificity among men were statistically significant ( Discussion: The ADA screening criteria exhibited high sensitivity for all groups and was marginally higher in women than men. Racial and ethnic differences in guideline performance among men were small and unlikely to have a significant impact on health equity. Future research could examine adoption of this recommendation in practice and examine its effects on treatment and clinical outcomes by sex, race, and ethnicity.
MeSH term(s)	Adult ; Male ; Humans ; Female ; United States/epidemiology ; Prediabetic State/diagnosis ; Prediabetic State/epidemiology ; Health Equity ; Diabetes Mellitus ; Ethnicity ; Risk Factors
Language	English
Publishing date	2023-10-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1279348
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Article ; Online: Screening for Prediabetes and Diabetes: Clinical Performance and Implications for Health Equity.

O'Brien, Matthew J / Zhang, Yan / Bailey, Stacy C / Khan, Sadiya S / Ackermann, Ronald T / Ali, Mohammed K / Benoit, Stephen R / Imperatore, Giuseppina / Holliday, Christopher S / Bullard, Kai McKeever

American journal of preventive medicine

2023 Volume 64, Issue 6, Page(s) 814–823

Abstract: Introduction: In 2021, the U.S. Preventive Services Task Force (USPSTF) recommended prediabetes and diabetes screening for asymptomatic adults aged 35-70 years with overweight/obesity, lowering the age from 40 years in its 2015 recommendation. The ... ...

Abstract	Introduction: In 2021, the U.S. Preventive Services Task Force (USPSTF) recommended prediabetes and diabetes screening for asymptomatic adults aged 35-70 years with overweight/obesity, lowering the age from 40 years in its 2015 recommendation. The USPSTF suggested considering earlier screening in racial and ethnic groups with high diabetes risk at younger ages or lower BMI. This study examined the clinical performance of these USPSTF screening recommendations as well as alternative age and BMI cutoffs in the U.S. adult population overall, and separately by race and ethnicity. Methods: Nationally representative data were collected from 3,243 nonpregnant adults without diagnosed diabetes in January 2017-March 2020 and analyzed from 2021 to 2022. Screening eligibility was based on age and measured BMI. Collectively, prediabetes and undiagnosed diabetes were defined by fasting plasma glucose ≥100 mg/dL or hemoglobin A Results: The 2021 criteria exhibited marginally higher sensitivity (58.6%, 95% CI=55.5, 61.6 vs 52.9%, 95% CI=49.7, 56.0) and lower specificity (69.3%, 95% CI=65.7, 72.2 vs 76.4%, 95% CI=73.3, 79.2) than the 2015 criteria overall, and within each racial and ethnic group. Screening at lower age and BMI thresholds resulted in even greater sensitivity and lower specificity, especially among Hispanic, non-Hispanic Black, and Asian adults. Screening all adults aged 35-70 years regardless of BMI yielded the most equitable performance across all racial and ethnic groups. Conclusions: The 2021 USPSTF screening criteria will identify more adults with prediabetes and diabetes in all racial and ethnic groups than the 2015 criteria. Screening all adults aged 35-70 years exhibited even higher sensitivity and performed most similarly by race and ethnicity, which may further improve early detection of prediabetes and diabetes in diverse populations.
MeSH term(s)	Adult ; Humans ; Diabetes Mellitus/epidemiology ; Ethnicity ; Health Equity ; Hispanic or Latino ; Prediabetic State/epidemiology ; Black or African American ; Asian ; Middle Aged ; Aged
Language	English
Publishing date	2023-03-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632646-8
ISSN	1873-2607 ; 0749-3797
ISSN (online)	1873-2607
ISSN	0749-3797
DOI	10.1016/j.amepre.2023.01.007
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Zs.A 2096: Show issues

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Article ; Online: A biological nanofoam: The wall of coniferous bisaccate pollen.

Cojocaru, Ruxandra / Mannix, Oonagh / Capron, Marie / Miller, C Giles / Jouneau, Pierre-Henri / Gallet, Benoit / Falconet, Denis / Pacureanu, Alexandra / Stukins, Stephen

Science advances

2022 Volume 8, Issue 6, Page(s) eabd0892

Abstract: The outer layer of the pollen grain, the exine, plays a key role in the survival of terrestrial plant life. However, the exine structure in different groups of plants remains enigmatic. Here, modern and fossil coniferous bisaccate pollen were examined to ...

Abstract	The outer layer of the pollen grain, the exine, plays a key role in the survival of terrestrial plant life. However, the exine structure in different groups of plants remains enigmatic. Here, modern and fossil coniferous bisaccate pollen were examined to investigate the detailed three-dimensional structure and properties of the pollen wall. X-ray nanotomography and volume electron microscopy are used to provide high-resolution imagery, revealing a solid nanofoam structure. Atomic force microscopy measurements were used to compare the pollen wall with other natural and synthetic foams and to demonstrate that the mechanical properties of the wall in this type of pollen are retained for millions of years in fossil specimens. The microscopic structure of this robust biological material has potential applications in materials sciences and also contributes to our understanding of the evolutionary success of conifers and other plants over geological time.
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abd0892
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Article ; Online: Response to Hajnal et al.

Davis, Jon F / Benoit, Stephen C

Obesity surgery

2013 Volume 23, Issue 8, Page(s) 1318

MeSH term(s)	Alcohol Drinking ; Animals ; Choice Behavior ; Ethanol/metabolism ; Gastric Bypass/adverse effects ; Ghrelin/blood ; Hippocampus/physiopathology ; Male ; Neural Pathways/physiopathology ; Obesity/surgery
Chemical Substances	Ghrelin ; Ethanol (3K9958V90M)
Language	English
Publishing date	2013-05-07
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1070827-3
ISSN	1708-0428 ; 0960-8923
ISSN (online)	1708-0428
ISSN	0960-8923
DOI	10.1007/s11695-013-0962-7
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Zs.A 3381: Show issues

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Article ; Online: Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond.

Fouks, Bertrand / Harrison, Mark C / Mikhailova, Alina A / Marchal, Elisabeth / English, Sinead / Carruthers, Madeleine / Jennings, Emily C / Chiamaka, Ezemuoka L / Frigard, Ronja A / Pippel, Martin / Attardo, Geoffrey M / Benoit, Joshua B / Bornberg-Bauer, Erich / Tobe, Stephen S

iScience

2023 Volume 26, Issue 10, Page(s) 107832

Abstract: Live birth (viviparity) has arisen repeatedly and independently among animals. We sequenced the genome and transcriptome of the viviparous Pacific beetle-mimic cockroach and performed comparative analyses with two other viviparous insect lineages, tsetse ...

Abstract	Live birth (viviparity) has arisen repeatedly and independently among animals. We sequenced the genome and transcriptome of the viviparous Pacific beetle-mimic cockroach and performed comparative analyses with two other viviparous insect lineages, tsetse flies and aphids, to unravel the basis underlying the transition to viviparity in insects. We identified pathways undergoing adaptive evolution for insects, involved in urogenital remodeling, tracheal system, heart development, and nutrient metabolism. Transcriptomic analysis of cockroach and tsetse flies revealed that uterine remodeling and nutrient production are increased and the immune response is altered during pregnancy, facilitating structural and physiological changes to accommodate and nourish the progeny. These patterns of convergent evolution of viviparity among insects, together with similar adaptive mechanisms identified among vertebrates, highlight that the transition to viviparity requires changes in urogenital remodeling, enhanced tracheal and heart development (corresponding to angiogenesis in vertebrates), altered nutrient metabolism, and shifted immunity in animal systems.
Language	English
Publishing date	2023-09-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107832
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Article: Outcomes of Patients with Lower Limb Loss after Using a Training Prosthesis: A Retrospective Case Series Study.

Pelzer, Doriane / Beaudart, Charlotte / Bornheim, Stephen / Maertens de Noordhout, Benoît / Schwartz, Cédric / Kaux, Jean-François

Healthcare (Basel, Switzerland)

2024 Volume 12, Issue 5

Abstract: The aim of this retrospective case series study was to investigate outcomes in patients with lower limb loss based on whether or not they used a training prosthesis (TP) during rehabilitation. The medical records of 171 consecutive patients admitted to ... ...

Abstract	The aim of this retrospective case series study was to investigate outcomes in patients with lower limb loss based on whether or not they used a training prosthesis (TP) during rehabilitation. The medical records of 171 consecutive patients admitted to rehabilitation hospitalization between January 2014 and December 2018 following a major amputation of the lower limb were reviewed. Patients were categorized into two groups: patients who underwent rehabilitation with a TP and patients who did not use a TP. Outcomes (i.e., discharge destination, length of stay, number of sockets required, and number of the size adaptation of each socket, as well as functional level) were compared between groups. Of the 171 patients, 126 underwent rehabilitation with a TP, and 45 patients underwent rehabilitation without any TP. In conclusion, we found that patients who used a TP had a significantly shorter hospital length of stay when compared to those who did not. This length of stay for patients with TP was not influenced by age but was lowered by a higher body mass index (BMI), tibial instead of femoral amputation, and the male gender. No association was found between the use of TP and discharge destination, functional level, number of socket modifications, and number of sockets required.
Language	English
Publishing date	2024-02-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2721009-1
ISSN	2227-9032
ISSN	2227-9032
DOI	10.3390/healthcare12050567
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Article ; Online: Broadening the phenotypic spectrum and physiological insights related to EIF2S3 variants.

Moortgat, Stephanie / Manfroid, Isabelle / Pendeville, Hélène / Freeman, Stephen / Bourdouxhe, Jordane / Benoit, Valérie / Merhi, Ahmad / Philippe, Christophe / Faivre, Laurence / Maystadt, Isabelle

Human mutation

2021 Volume 42, Issue 7, Page(s) 827–834

Abstract: ... We identified a novel missense variant (c.433A>G, p.(Met145Val)) in EIF2S3 in a mildly affected patient. Studies ...

Abstract	Mental deficiency, epilepsy, hypogonadism, microcephaly, and obesity syndrome is a severe X-linked syndrome caused by pathogenic variants in EIF2S3. The gene encodes the γ subunit of the eukaryotic translation initiation factor-2, eIF2, essential for protein translation. A recurrent frameshift variant is described in severely affected patients while missense variants usually cause a moderate phenotype. We identified a novel missense variant (c.433A>G, p.(Met145Val)) in EIF2S3 in a mildly affected patient. Studies on zebrafish confirm the pathogenicity of this novel variant and three previously published missense variants. CRISPR/Cas9 knockout of eif2s3 in zebrafish embryos recapitulate the human microcephaly and show increased neuronal cell death. Abnormal high glucose levels were identified in mutant embryos, caused by beta cell and pancreatic progenitor deficiency, not related to apoptosis. Additional studies in patient-derived fibroblasts did not reveal apoptosis. Our results provide new insights into disease physiopathology, suggesting tissue-dependent mechanisms.
MeSH term(s)	Animals ; Genitalia ; Humans ; Mental Retardation, X-Linked/genetics ; Mutation ; Phenotype ; Zebrafish/genetics
Language	English
Publishing date	2021-05-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1126646-6
ISSN	1098-1004 ; 1059-7794
ISSN (online)	1098-1004
ISSN	1059-7794
DOI	10.1002/humu.24215
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Zs.A 3586: Show issues

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Article ; Online: Terpene polyacrylate TPA5 shows favorable molecular hydrodynamic properties as a potential bioinspired archaeological wood consolidant.

Cutajar, Michelle / Andriulo, Fabrizio / Thomsett, Megan R / Moore, Jonathan C / Couturaud, Benoit / Howdle, Steven M / Stockman, Robert A / Harding, Stephen E

Scientific reports

2021 Volume 11, Issue 1, Page(s) 7343

Abstract: There is currently a pressing need for the development of novel bioinspired consolidants for waterlogged, archaeological wood. Bioinspired materials possess many advantages, such as biocompatibility and sustainability, which makes them ideal to use in ... ...

Abstract	There is currently a pressing need for the development of novel bioinspired consolidants for waterlogged, archaeological wood. Bioinspired materials possess many advantages, such as biocompatibility and sustainability, which makes them ideal to use in this capacity. Based on this, a polyhydroxylated monomer was synthesised from α-pinene, a sustainable terpene feedstock derived from pine trees, and used to prepare a low molar mass polymer TPA5 through free radical polymerisation. This polymer was extensively characterised by NMR spectroscopy (chemical composition) and molecular hydrodynamics, primarily using analytical ultracentrifugation reinforced by gel filtration chromatography and viscometry, in order to investigate whether it would be suitable for wood consolidation purposes. Sedimentation equilibrium indicated a weight average molar mass M
Language	English
Publishing date	2021-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-86543-1
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