60 results on '"J, Just"'
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2. Urticaire chronique et allergie : rationnel pour une exploration ciblée
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H Chabane, J Vitte, C Dzviga, C Lambert, A Sarrat, S Lefevre, G Dalampira, E Seve, C Klingebiel, P Nicaise-Roland, C Palussière, J Bienvenu, R Couderc, P Demoly, and J Just
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Immunology and Allergy - Published
- 2022
3. Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Partie 2 : allergie respiratoire
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H. Chabane, C. Metz-Favre, C. Klingebiel, C. Mailhol, F. Le Pabic, C. Castelain, C. Palussière, B. Uring-Lambert, C. Bouz, G. Dalampira, A. Sarrat, E. Seve, S. Lefevre, C. Dzviga, P. Nicaise-Roland, C. Lambert, J. Bienvenu, R. Couderc, P. Demoly, and J. Just
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Immunology and Allergy - Published
- 2021
4. Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Partie 5 : allergie aux piqûres et morsures d’arthropodes et autres allergies ou pathologies
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Joana Vitte, C. Dzviga, C. Palussière, C. Lambert, S. Lefevre, Rémy Couderc, Pascal Demoly, P. Nicaise-Roland, J. Just, C. Klingebiel, A. Sarrat, G. Dalampira, Jacques Bienvenu, E. Seve, and H. Chabane
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,Immunology and Allergy - Abstract
Resume Les examens biologiques d’allergie contribuent de facon significative au diagnostic et au suivi des allergies aux piqures et morsures d’arthropodes. Les dosages d’IgE specifiques apportent la preuve d’un mecanisme allergique IgE-dependant. L’utilisation rationnelle des outils biologiques disponibles selon les donnees actualisees de la science est a meme de garantir l’efficience diagnostique. Le mesusage de la biologie de l’allergie et/ou leur interpretation erronee risque d’aboutir a des attitudes therapeutiques inadaptees. Consciente de cet enjeu, la Societe francaise d’allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l’actualisation des recommandations de biologie de l’allergie, les precedentes recommandations elaborees en 2005 par la Haute autorite de sante (HAS) etant devenues en partie obsoletes en raison de l’evolution des techniques et concepts. La methodologie utilisee est celle des recommandations pour la pratique clinique (RPC) elaboree par la HAS, meme si le texte n’a pas ete labellise par celle institution. Le groupe de travail a redige 8 recommandations gradees sur l’allergie aux piqures et morsures d’arthropodes et 5 recommandations gradees sur d’autres pathologies immuno-allergiques ou frontiere. Bien que non exhaustives, ces 13 questions repondent aux preoccupations les plus courantes des prescripteurs qu’ils soient allergologues ou non, tout en tenant compte du contexte reglementaire francais.
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- 2021
5. Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Partie 3 : allergie alimentaire
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H. Chabane, G. Dalampira, C. Klingebiel, S. Lefevre, C. Palussière, P. Nicaise-Roland, C. Metz-Favre, M. Bouvier, A. Sarrat, E. Seve, C. Delebarre-Sauvage, C. Dzviga, J. Bienvenu, R. Couderc, P. Demoly, and J. Just
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Immunology and Allergy - Published
- 2021
6. Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Partie 4 : allergie aux médicaments
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E. Seve, P. Nicaise-Roland, J. Just, C. Delebarre-Sauvage, C. Klingebiel, Pascal Demoly, S. Lefevre, Jacques Bienvenu, G. Dalampira, M. Bouvier, C. Dzviga, C. Palussière, A. Sarrat, H. Chabane, Carine Metz-Favre, and Rémy Couderc
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,Immunology and Allergy - Abstract
Resume Contrairement aux allergies respiratoires, alimentaires et aux venins d’hymenopteres qui concernent des allergenes proteiques, la prise en charge des allergies aux medicaments necessite rarement le recours aux examens biologiques pour obtenir la preuve d’un mecanisme allergique IgE-dependant. Un nombre tres restreint de dosages d’IgE specifiques de medicaments est disponible car la grande majorite des medicaments sont des haptenes. L’utilisation rationnelle des outils biologiques disponibles selon les donnees actualisees de la science est a meme de garantir l’efficience diagnostique. Le mesusage de la biologie de l’allergie et/ou leur interpretation erronee risque d’aboutir a des attitudes therapeutiques inadaptees voire dangereuses. Consciente de cet enjeu, la Societe francaise d’allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l’actualisation des recommandations de biologie de l’allergie, les precedentes recommandations elaborees en 2005 par la Haute autorite de sante (HAS) etant devenues en partie obsoletes en raison de l’evolution des techniques et concepts. La methodologie utilisee est celle des recommandations pour la pratique clinique (RPC) elaboree par la HAS, meme si le texte n’a pas ete labellise par celle institution. Le groupe de travail a redige 11 recommandations gradees sur l’allergie aux medicaments. Bien que non exhaustives, ces 11 questions repondent aux preoccupations les plus courantes des prescripteurs qu’ils soient allergologues ou non pour la prise en charge des patients ayant une suspicion d’allergie aux medicaments, tout en tenant compte du contexte reglementaire francais.
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- 2021
7. Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Texte court
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H. Chabane, C. Klingebiel, G. Dalampira, A. Sarrat, S. Lefevre, C. Dzviga, C. Metz-Favre, J. Vitte, P. Nicaise-Roland, E. Seve, C. Palussière, C. Lambert, P-A. Apoil, M. Bouvier, C. Castelain, F. Le Pabic, C. Delebarre-Sauvage, B. Uring-Lambert, L. Garnier, C. Mailhol, C. Bouz, J.C. Farouz, J. Bienvenu, R. Couderc, P. Demoly, and J. Just
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Immunology and Allergy - Published
- 2021
8. Allergie au sésame : revue générale
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S. Saf, J. Just, G. Benoist, E. Bidat, S. Honjoya, and N. Cottel
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Immunology and Allergy - Abstract
Resume Le sesame est un allergene a connaitre car present dans notre alimentation mais aussi dans certains produits pharmaceutiques et cosmetiques. L’allergie au sesame a une prevalence faible mais est potentiellement severe avec un risque eleve d’anaphylaxie. Les tests cutanes et les IgE specifiques sont de valeur inconstante ; la place des allergenes recombinants reste a mieux preciser. Le test de provocation par voie orale tient une place essentielle en cas de doute diagnostique et pour evaluer une eventuelle guerison dont le taux est autour de 20 %. Il necessite une equipe rompue a la prise en charge de l’anaphylaxie. Un prick test superieur a 14 mm semble etre associe a un taux de positivite du TPO de l’ordre de 95 %. La prise en charge repose avant tout sur l’eviction du sesame. Une liste peut etre remise aux familles afin de notifier les principales sources d’exposition. L’immunotherapie orale pourrait apparaitre comme une perspective interessante mais doit etre actuellement reservee aux centres experts.
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- 2021
9. Organisation des structures de soins transversales en allergologie en France en 2020
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Frédéric Bérard, Martine Morisset, Philippe Bonniaud, E. Collet, S. Lefevre, J. Just, L. Collin, and F. de Blay
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030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Immunology and Allergy - Abstract
Resume Introduction Les allergies touchent 25 % de la population generale avec une augmentation des allergies severes. Le developpement en France de structures de soins transversales en allergologie pour une prise en charge pluridisciplinaire des patients repond a un besoin de sante publique. Notre travail a pour but de faire un etat des lieux de ces structures. Methodes Enquete descriptive par questionnaire envoye aux chefs de services de structures de soins soit avec une activite principale en allergologie, soit avec une activite variee en allergologie. L’enquete portait sur l’organisation administrative, les equipes medicales et paramedicales, l’offre de soins et les moyens techniques des structures. Resultats Trente-sept structures ont pu etre analysees dont 27 avec une activite principale en allergologie et 10 avec une activite variee en allergologie. Pour les premieres, le nombre de medecins varie de 1 a 16 et les equivalents temps pleins infirmier de 0,8 a 5,9. Les nombres d’hospitalisations de jour et de consultations annuelles sont respectivement de 1049 (220 a 3275) et 3561 (609 a 13 674). Un tiers du recrutement des patients est hors departement. Toutes les structures avec une activite principale en allergologie realisent des explorations sur les allergies alimentaires, medicamenteuses et aux pneumallergenes mais seulement 81 % et 74 % assurent respectivement la prise en charge des allergies aux hymenopteres et des eczemas de contact. Conclusions Cette etude constitue un premier etat des lieux des structures hospitalieres transversales en allergologie en France afin de permettre de guider le developpement d’Unites transversales d’allergologie.
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- 2021
10. Recommendations for the prescription and interpretation of laboratory tests that can be used in the diagnosis or monitoring of allergies, available in France. Part 1: Preamble
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H. Chabane, J. Vitte, A. Sarrat, E. Seve, P.-A. Apoil, G. Dalampira, C. Palussière, C. Klingebiel, S. Lefevre, P. Nicaise-Roland, C. Dzviga, C. Lambert, C. Metz-Favre, M. Bouvier, C. Castelain, F. Le Pabic, C. Delebarre-Sauvage, B. Uring-Lambert, L. Garnier, C. Bouz, C. Mailhol, J.C. Farouz, J. Bienvenu, R. Couderc, P. Demoly, J. Just, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'Université de Bourgogne (LPUB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Synlab Provence, Laboratoire de psychologie de l'interaction et des relations intersubjectives (INTERPSY), Université de Lorraine (UL), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Strasbourg, Complexe de recherche interprofessionnel en aérothermochimie (CORIA), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Eurofins Biomnis
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[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Immunology and Allergy ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience; Allergy laboratory tests make an important contribution to the diagnosis and monitoring of allergic diseases. The increase in the prevalence of these diseases in the French population in recent decades and the increasingly frequent use of biological diagnostics requires the optimisation of the use of this tool. Its rational use according to updated scientific data and an approach favoring the cost/benefit ratio can guarantee diagnostic efficiency. Aware of this issue, the French society of allergology (SFA) has set up a multidisciplinary task force to update allergy biology recommendations, the previous recommendations drawn up in 2005 by the High authority for health (HAS) having become partly obsolete due to the evolution of techniques and concepts. The methodology used is that of the recommendations for clinical practice (RPC) developed by the HAS, even if the text has not been labelled by that institution. The working group drafted 73 graded recommendations and a preamble with 6 general questions. Although not exhaustive, these 79 questions answer the most common concerns of prescribers whether they are allergists or not for the management of patients with allergies or with suspected allergies, while taking into account the French regulatory context.; Les examens biologiques d’allergie contribuent de façon importante au diagnostic et au suivi des maladies allergiques. L’augmentation de la prévalence de ces maladies dans la population française durant les dernières décennies et le recours de plus en plus fréquent au diagnostic biologique nécessite l’optimisation de l’utilisation de cet outil. Son utilisation rationnelle selon les données actualisées de la science et une démarche privilégiant le rapport coût/bénéfice sont à même de garantir l’efficience diagnostique. Consciente de cet enjeu, la Société française d’allergologie (SFA) a mis en place un groupe de travail multidisciplinaire pour l’actualisation des recommandations de biologie de l’allergie, les précédentes recommandations élaborées en 2005 par la Haute Autorité de santé (HAS) étant devenues en partie obsolètes en raison de l’évolution des techniques et concepts. La méthodologie utilisée est celle des recommandations pour la pratique clinique (RPC) élaborée par la HAS, même si le texte n’a pas été labellisé par celle institution. Le groupe de travail a rédigé 73 recommandations gradées et un préambule comportant 6 questions d’ordre général. Bien que non exhaustives, ces 79 questions répondent aux préoccupations les plus courantes des prescripteurs qu’ils soient allergologues ou non pour la prise en charge des patients allergiques ou ayant une suspicion d’allergie, tout en tenant compte du contexte réglementaire français.
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- 2021
11. Publisher Correction: Indo-Pacific Walker circulation drove Pleistocene African aridification
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H. J. L. van der Lubbe, I. R. Hall, S. Barker, S. R. Hemming, T. F. Baars, A. Starr, J. Just, B. C. Backeberg, and J. C. A. Joordens
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Multidisciplinary - Abstract
In this Article, a processing error led to the wrong versions of Fig. 3 and Extended Data Fig. 4 being published. Figure 3e did not include the entirety of the eastern Africa soil carbonate δ13C database as compiled by ref.13. Fig. 3 of the original Article has been corrected, and Fig. 1 of this Amendment shows the original and corrected Fig. 3 side by side, for transparency. In the Methods section of the original Article, there are further details about how this record has been produced. The last paragraph of the Methods has been corrected; the original text was: “On the basis of ref.13, time series of δ13C values from soil carbonate were combined for the Omo-Turkana Basin and the southern Kenyan-Tanzanian sites using their medians, and interquartile ranges using six-data-point bins.” Furthermore, the original version of Extended Data Fig. 4 did not display data from eastern African hominin site Afar; the figure and caption have been updated accordingly, and the original and corrected versions are shown as Fig. 2 to this Amendment. These changes do not alter any inferences drawn from the data. These errors have been corrected in the online version of the Article.
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- 2022
12. Erratum à l’article « Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Texte court » [Rev. Fr. Allergol. 61 (7) (2021) 436–58]
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H. Chabane, C. Klingebiel, G. Dalampira, A. Sarrat, S. Lefevre, C. Dzviga, C. Metz-Favre, J. Vitte, P. Nicaise-Roland, E. Seve, C. Palussière, C. Lambert, P.-A. Apoil, M. Bouvier, C. Castelain, F. Le Pabic, C. Delebarre-Sauvage, B. Uring-Lambert, L. Garnier, C. Mailhol, C. Bouz, J.C. Farouz, J. Bienvenu, R. Couderc, P. Demoly, and J. Just
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Immunology and Allergy - Published
- 2022
13. Suboptimal basophil activation by molecular allergens can lead to false-negative basophil activation test
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Y. Chantran, N. Cottel, G. Germain, S. Saf, A. Lemoine, N. Lambert, M. Bourgoin-Heck, J. Just, and S. Wanin
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Immunology and Allergy - Published
- 2022
14. Operando XANES Reveals the Chemical State of Iron-Oxide Monolayers During Low-Temperature CO Oxidation.
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Gajdek D, Wallander HJ, Abbondanza G, Harlow GS, Gustafson J, Blomberg S, Carlsson PA, Just J, Lundgren E, and Merte LR
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We have used grazing incidence X-ray absorption near edge spectroscopy (XANES) to investigate the behavior of monolayer FeOx films on Pt(111) under near ambient pressure CO oxidation conditions with a total gas pressure of 1 bar. Spectra indicate reversible changes during oxidation and reduction by O2 and CO at 150ºC, attributed to a transformation between FeO bilayer and FeO2 trilayer phases. The trilayer phase is also reduced upon heating in CO+O2, consistent with a Mars-van-Krevelen type mechanism for CO oxidation. At higher temperatures, the monolayer film dewets the surface, resulting in a loss of the observed reducibility. A similar iron oxide film prepared on Au(111) shows little sign of reduction or oxidation under the same conditions. The results highlight the unique properties of monolayer FeO and the importance of the Pt support in this reaction. The study furthermore demonstrates the power of grazing-incidence XAFS for in situ studies of these model catalysts under realistic conditions., (© 2024 Wiley‐VCH GmbH.)
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- 2024
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15. Integration of long-read sequencing, DNA methylation and gene expression reveals heterogeneity in Y chromosome segment lengths in phenotypic males with 46,XX testicular disorder/difference of sex development.
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Berglund A, Johannsen EB, Skakkebæk A, Chang S, Rohayem J, Laurentino S, Hørlyck A, Drue SO, Bak EN, Fedder J, Tüttelmann F, Gromoll J, Just J, and Gravholt CH
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- Male, Humans, Female, Adult, 46, XX Testicular Disorders of Sex Development genetics, Adolescent, Child, Young Adult, Child, Preschool, DNA Methylation, Chromosomes, Human, Y genetics, Phenotype
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Background: 46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive., Methods: We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10)., Results: We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7-2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size., Conclusion: This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome., (© 2024. The Author(s).)
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- 2024
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16. HSP60 chaperone deficiency disrupts the mitochondrial matrix proteome and dysregulates cholesterol synthesis.
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Cömert C, Kjær-Sørensen K, Hansen J, Carlsen J, Just J, Meaney BF, Østergaard E, Luo Y, Oxvig C, Schmidt-Laursen L, Palmfeldt J, Fernandez-Guerra P, and Bross P
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- Animals, Humans, Fibroblasts metabolism, HEK293 Cells, Larva metabolism, Chaperonin 60 metabolism, Chaperonin 60 genetics, Cholesterol metabolism, Cholesterol biosynthesis, Mitochondria metabolism, Mitochondrial Proteins metabolism, Mitochondrial Proteins genetics, Proteome metabolism, Zebrafish
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Objective: Mitochondrial proteostasis is critical for cellular function. The molecular chaperone HSP60 is essential for cell function and dysregulation of HSP60 expression has been implicated in cancer and diabetes. The few reported patients carrying HSP60 gene variants show neurodevelopmental delay and brain hypomyelination. Hsp60 interacts with more than 260 mitochondrial proteins but the mitochondrial proteins and functions affected by HSP60 deficiency are poorly characterized., Methods: We studied two model systems for HSP60 deficiency: (1) engineered HEK cells carrying an inducible dominant negative HSP60 mutant protein, (2) zebrafish HSP60 knockout larvae. Both systems were analyzed by RNASeq, proteomics, and targeted metabolomics, and several functional assays relevant for the respective model. In addition, skin fibroblasts from patients with disease-associated HSP60 variants were analyzed by proteomics., Results: We show that HSP60 deficiency leads to a differentially downregulated mitochondrial matrix proteome, transcriptional activation of stress responses, and dysregulated cholesterol biosynthesis. This leads to lipid accumulation in zebrafish knockout larvae., Conclusions: Our data provide a compendium of the effects of HSP60 deficiency on the mitochondrial matrix proteome. We show that HSP60 is a master regulator and modulator of mitochondrial functions and metabolic pathways. HSP60 dysfunction also affects cellular metabolism and disrupts the integrated stress response. The effect on cholesterol synthesis explains the effect of HSP60 dysfunction on myelination observed in patients carrying genetic variants of HSP60., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Aarhus University. Published by Elsevier GmbH.. All rights reserved.)
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- 2024
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17. High burden of respiratory allergy in children warrants early identification and treatment with allergen immunotherapy.
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Hamelmann E, Csonka P, Roberts G, Vogelberg C, Cichocka-Jarosz E, Just J, and Jeseňák M
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Respiratory allergy often begins in childhood and most commonly manifests as allergic rhinitis (upper airways) and/or asthma (lower airways). Children with upper respiratory allergy often suffer from coexisting asthma, and other comorbidities ranging from gastrointestinal disorders to emotional/mental health disorders. Consequently, the disease burden is considerable and profoundly impacts a child's daily life. Early identification and appropriate management are important to reduce disease burden, lower the risk of disease progression and additional comorbidities, and protect the child's future well-being. A window of opportunity for halting disease progression may open in the early stages of allergic disease and underlines the importance of early diagnosis and treatment of children at risk. This review offers advice on identifying children with a high disease burden who would benefit from early intervention. Allergen immunotherapy (AIT) modifies the cause of respiratory allergy and prevents disease progression. In clinical practice, AIT could be considered as an early treatment for eligible children, to achieve long-term symptom control and disease modification., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. EH has received grants from the German Ministry of Education and Research (BMBF), Network University Medicine (NUM), Ministry of Health and Social Affairs of Nordrhein-Westfalen (MAGS), and Federal Joint Committee (G-BA), and has received fees for lectures and consulting activities from Abbvie, Aimmune, ALK-Abelló, Allergopharma, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, DBV, GSK, LETI Pharma, Novartis, Nutricia, nutrimmun, Sanofi, and Stallergenes. EH is the Vice President of the German Allergy Society (DGAKI) and the President of the German Asthma Net (GAN e.V.). PC has received fees for consulting activities from ALK-Abelló, Thermo Fisher Scientific, Orion Pharma, and GSK. GR has received fees for lectures and consulting activities from ALK-Abelló, research support from AstraZeneca, and has been supported by Allergen Therapeutics. CV has received grants from the German Research Foundation (DFG), and has received fees for lectures and consulting activities from Abbvie, Aimmune, ALK-Abelló, Allergopharma, AstraZeneca, Allergy Therapeutics, Bencard Allergie, Boehringer Ingelheim, DBV, LETI Pharma, Novartis, Orion Pharma, Sanofi Aventis, and Stallergenes. EC-J is a member of the ALK-Abelló Paediatric Advisory Board and has received fees for lectures and consulting activities from ALK-Abelló, Stallergenes-Greer, GSK, Thermofisher Scientific, and Allergopharma. JJ is a member of the ALK-Abelló Paediatric Advisory Board and has received fees for lectures and consulting activities from ALK-Abelló, Stallergenes-Greer, GSK, Novartis, AstraZeneca, and Zambon. MJ has received consultancy/speaker honoraria from ALK-Abelló, Berlin-Chemie, Stallergenes-Greer, GSK, and Viatris, and is a member of Advisory Boards for ALK-Abelló, Stallergenes-Greer, and Viatris., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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18. The AUREX cell: a versatile operando electrochemical cell for studying catalytic materials using X-ray diffraction, total scattering and X-ray absorption spectroscopy under working conditions.
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Frank S, Ceccato M, Jeppesen HS, Marks MJ, Nielsen MLN, Lu R, Gammelgaard JJ, Quinson J, Sharma R, Jensen JS, Hjelme S, Friberg Klysner C, Billinge SJL, Just J, Gjørup FH, Catalano J, and Lock N
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Understanding the structure-property relationship in electrocatalysts under working conditions is crucial for the rational design of novel and improved catalytic materials. This paper presents the Aarhus University reactor for electrochemical studies using X-rays (AUREX) operando electrocatalytic flow cell, designed as an easy-to-use versatile setup with a minimal background contribution and a uniform flow field to limit concentration polarization and handle gas formation. The cell has been employed to measure operando total scattering, diffraction and absorption spectroscopy as well as simultaneous combinations thereof on a commercial silver electrocatalyst for proof of concept. This combination of operando techniques allows for monitoring of the short-, medium- and long-range structure under working conditions, including an applied potential, liquid electrolyte and local reaction environment. The structural transformations of the Ag electrocatalyst are monitored with non-negative matrix factorization, linear combination analysis, the Pearson correlation coefficient matrix, and refinements in both real and reciprocal space. Upon application of an oxidative potential in an Ar-saturated aqueous 0.1 M KHCO
3 /K2 CO3 electrolyte, the face-centered cubic (f.c.c.) Ag gradually transforms first to a trigonal Ag2 CO3 phase, followed by the formation of a monoclinic Ag2 CO3 phase. A reducing potential immediately reverts the structure to the Ag (f.c.c.) phase. Following the electrochemical-reaction-induced phase transitions is of fundamental interest and necessary for understanding and improving the stability of electrocatalysts, and the operando cell proves a versatile setup for probing this. In addition, it is demonstrated that, when studying electrochemical reactions, a high energy or short exposure time is needed to circumvent beam-induced effects., Competing Interests: There are no conflicts of interest to declare., (© Sara Frank et al. 2024.)- Published
- 2024
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19. Rational Design of Multinary Metal Chalcogenide Bi 0.4 Sb 1.6 Te 3 Nanocrystals for Efficient Potassium Storage.
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Zhang L, Liu J, Zhai Y, Zhang S, Wang W, Li G, Sun L, Li H, Qi S, Chen S, Wang R, Ma Q, Just J, and Zhang C
- Abstract
Multinary metal chalcogenides hold considerable promise for high-energy potassium storage due to their numerous redox reactions. However, challenges arise from issues such as volume expansion and sluggish kinetics. Here, a design featuring a layered ternary Bi
0.4 Sb1.6 Te3 anchored on graphene layers as a composite anode, where Bi atoms act as a lattice softening agent on Sb, is presented. Benefiting from the lattice arrangement in Bi0.4 Sb1.6 Te3 and structure, Bi0.4 Sb1.6 Te3 /graphene exhibits a mitigated expansion of 28% during the potassiation/depotassiation process and demonstrates facile K+ ion transfer kinetics, enabling long-term durability of 500 cycles at various high rates. Operando synchrotron diffraction patterns and spectroscopies including in situ Raman, ex situ adsorption, and X-ray photoelectron reveal multiple conversion and alloying/dealloying reactions for potassium storage at the atomic level. In addition, both theoretical calculations and electrochemical examinations elucidate the K+ migration pathways and indicate a reduction in energy barriers within Bi0.4 Sb1.6 Te3 /graphene, thereby suggesting enhanced diffusion kinetics for K+ . These findings provide insight in the design of durable high-energy multinary tellurides for potassium storage., (© 2024 Wiley‐VCH GmbH.)- Published
- 2024
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20. Mild liver dysfunction in Klinefelter syndrome is associated with abdominal obesity and elevated lipids but not testosterone treatment.
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Øzdemir CM, Ridder LO, Chang S, Fedder J, Just J, Gravholt CH, and Skakkebæk A
- Abstract
Context: Klinefelter syndrome (KS) is associated with hypergonadotropic hypogonadism, which contributes to characteristic phenotypical manifestations including metabolic alterations. Extensive research has demonstrated important associations between androgens and liver function., Objectives: Investigation of the association between metabolic parameters, sex hormones and liver function in males with KS, both treated (T-KS) and untreated (U-KS) and healthy control males., Methods: A total of 65 KS males were recruited, of which 32 received testosterone replacement therapy (TRT). Also, 69 healthy controls were recruited. We used alanine aminotransferase (ALAT), alkaline phosphatase and PP (prothrombin-proconvertin time ratio) as the main liver markers. Multivariable regression was performed within the three groups. All statistics were calculated using STATA. Principal component analysis was utilized to demonstrate the interconnected patterns among all measured biomarkers, and to elucidate how the different groups were linked to these patterns., Results: Higher levels of main liver markers were observed in U-KS compared to controls, with no significant differences between U-KS and T-KS. T-KS had lower abdominal fat, total cholesterol, and LDL cholesterol than U-KS. Using multivariable models, variation in ALAT in U-KS was explained by HOMA2%S; in T-KS by BMI and SHBG; and in controls by hip circumference and estradiol. We found no multivariable models explaining variation in PP in U-KS; in T-KS, PP was explained by BMI and LDL cholesterol, and in controls by total cholesterol. Using principal component analysis U-KS was positively associated to D1 (an obese profile, which also included ALAT) and controls negatively associated with D1 (non-obese profile)., Conclusion: KS males have mild liver dysfunction reflected by a significant increase in the main liver markers and decrease in albumin. The presented data underscore a primary role of metabolic conditions including obesity, insulin resistance and unfavourable lipid profile, in the elevated liver function markers seen in males with KS. Whether TRT can improve liver function in KS warrants further studies. Our findings, highlight that an evaluation of the liver function should be part of the clinical care in males with KS., (© 2024. The Author(s).)
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- 2024
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21. Testosterone Replacement Therapy in Klinefelter Syndrome-Follow-up Study Associating Hemostasis and RNA Expression.
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Chang S, Just J, Skakkebæk A, Johannsen EB, Fedder J, Gravholt CH, and Münster AB
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- Male, Humans, Follow-Up Studies, Thrombomodulin genetics, Thrombomodulin therapeutic use, Thrombin metabolism, Testosterone therapeutic use, Hemostasis genetics, Fibrinogen, RNA, Klinefelter Syndrome complications, Klinefelter Syndrome drug therapy, Klinefelter Syndrome genetics, Hypogonadism drug therapy, Hypogonadism genetics, Hypogonadism complications, Thrombosis
- Abstract
Background: Men with Klinefelter syndrome (KS) develop hypergonadotropic hypogonadism, are in need of testosterone replacement therapy (TRT), and present with a more than 4-fold increased risk of thrombosis. TRT in KS has the potential to modify thrombotic risk, but data are scarce., Aim: To assess effects of 18 months of TRT on hemostasis in KS and identify genes associated with the prothrombotic phenotype., Methods: Untreated and TRT-treated men with KS were included at baseline and matched to healthy controls. TRT was initiated in untreated KS and all groups were reassessed after 18 months of follow-up. Thrombin generation was evaluated with or without thrombomodulin, and fibrin clot lysis was evaluated by turbidity measurements. RNA expression was assessed in blood, fat, and muscle tissue of patients with TRT-treated KS and controls., Results: Thrombin generation with thrombomodulin was slightly increased in untreated KS, but overall KS was not associated with a hypercoagulable state. KS presented with fibrinolytic impairment associated with higher body fat and higher levels of fibrinogen. Eighteen months of TRT in KS was associated with a reduction in body fat and fibrinogen, attenuating the prothrombotic profile. The expression of ENPP4 was higher in men with KS and served as a key player among a group of genes associated with impaired fibrinolysis., Conclusion: KS is associated with a specific expression profile contributing to fibrinolytic impairment and increased thrombotic risk in the patients. TRT in patients with KS has the potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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22. Cell layer-specific expression of the homeotic MADS-box transcription factor PhDEF contributes to modular petal morphogenesis in petunia.
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Chopy M, Cavallini-Speisser Q, Chambrier P, Morel P, Just J, Hugouvieux V, Rodrigues Bento S, Zubieta C, Vandenbussche M, and Monniaux M
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- Plant Proteins metabolism, Gene Expression Regulation, Flowers physiology, Morphogenesis genetics, Gene Expression Regulation, Plant genetics, Transcription Factors genetics, Transcription Factors metabolism, Petunia genetics, Petunia metabolism
- Abstract
Floral homeotic MADS-box transcription factors ensure the correct morphogenesis of floral organs, which are organized in different cell layers deriving from distinct meristematic layers. How cells from these distinct layers acquire their respective identities and coordinate their growth to ensure normal floral organ morphogenesis is unresolved. Here, we studied petunia (Petunia × hybrida) petals that form a limb and tube through congenital fusion. We identified petunia mutants (periclinal chimeras) expressing the B-class MADS-box gene DEFICIENS in the petal epidermis or in the petal mesophyll, called wico and star, respectively. Strikingly, wico flowers form a strongly reduced tube while their limbs are almost normal, while star flowers form a normal tube but greatly reduced and unpigmented limbs, showing that petunia petal morphogenesis is highly modular. These mutants highlight the layer-specific roles of PhDEF during petal development. We explored the link between PhDEF and petal pigmentation, a well-characterized limb epidermal trait. The anthocyanin biosynthesis pathway was strongly downregulated in star petals, including its major regulator ANTHOCYANIN2 (AN2). We established that PhDEF directly binds to the AN2 terminator in vitro and in vivo, suggesting that PhDEF might regulate AN2 expression and therefore petal epidermis pigmentation. Altogether, we show that cell layer-specific homeotic activity in petunia petals differently impacts tube and limb development, revealing the relative importance of the different cell layers in the modular architecture of petunia petals., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)
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- 2024
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23. Patient Perspectives on Pharmacotherapy of Alcohol Dependence.
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Wellensiek J, Specka M, Just J, Banger M, Bonnet U, and Scherbaum N
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- Humans, Female, Middle Aged, Male, Acamprosate therapeutic use, Naltrexone therapeutic use, Disulfiram therapeutic use, Taurine therapeutic use, Alcoholism drug therapy, Alcohol Deterrents therapeutic use, Substance Withdrawal Syndrome drug therapy
- Abstract
Introduction: Pharmacotherapy with drugs like naltrexone or acamprosate is a well-evaluated element in the treatment of alcohol dependence (AD). However, in many countries, these medications are rarely administered. The objective of the present study was to identify from patients' perspective factors that prevent the initiation and compliance with pharmacological treatment of AD., Methods: Patients from inpatient alcohol withdrawal treatment underwent a standardized interview. Questions included socio-demographic data, history of AD, treatment history, knowledge and personal experience regarding pharmacotherapy of AD, and personal views about the causes of AD., Results: Three hundred patients (mean age 47.3 years, 27.7% female, mean duration of AD 8.9 years, 67% with a history of previous inpatient withdrawal treatment) were included. The majority of patients (58.7%) already knew drugs for the pharmacotherapy of AD. Thirty percent had ever used such medications, most often acamprosate. Except for disulfiram, pharmacotherapy of AD had lasted only a few weeks, on average. Medication usually had been applied without additional psychotherapy. No severe side effects were reported. Patients had often stopped pharmacotherapy on their own, when assuming they had reached stable abstinence. Openness to start pharmacotherapy for AD was currently stated by 67% of the total sample. In multiple logistic regression, openness was predicted by having a concept of AD as a medical disease and by a shorter duration of AD., Discussion: To improve the administration of pharmacotherapy for AD implementation strategies should be systematically developed and evaluated with a focus on the concept of AD as a medical disease., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
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- 2024
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24. BOSC 2023, the 24th annual Bioinformatics Open Source Conference.
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Harris NL, Fields CJ, Hokamp K, Just J, Khetani R, Maia J, Ménager H, Munoz-Torres MC, Unni D, and Williams J
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- Humans, Information Dissemination, Computational Biology, Software
- Abstract
The 24th annual Bioinformatics Open Source Conference ( BOSC 2023) was part of the 2023i conference on Intelligent Systems for Molecular Biology and the European Conference on Computational Biology (ISMB/ECCB 2023). Launched in 2000 and held yearly since, BOSC is the premier meeting covering open-source bioinformatics and open science. Like ISMB 2022, the 2023 meeting was a hybrid conference, with the in-person component hosted in Lyon, France. ISMB/ECCB attracted a near-record number of attendees, with over 2100 in person and about 900 more online. Approximately 200 people participated in BOSC sessions. In addition to 43 talks and 49 posters, BOSC featured two keynotes: Sara El-Gebali, who spoke about "A New Odyssey: Pioneering the Future of Scientific Progress Through Open Collaboration", and Joseph Yracheta, who spoke about "The Dissonance between Scientific Altruism & Capitalist Extraction: The Zero Trust and Federated Data Sovereignty Solution." Once again, a joint session brought together BOSC and the Bio-Ontologies COSI. The conference ended with a panel on Open and Ethical Data Sharing. As in prior years, BOSC was preceded by a CollaborationFest, a collaborative work event that brought together about 40 participants interested in synergistically combining ideas, shaping project plans, developing software, and more., Competing Interests: Competing interests: BOSC 2023 was supported in part by the sponsors mentioned in the Acknowledgements. However, this had no influence on abstract selection. Abstracts submitted by authors affiliated with current or past sponsoring companies were subjected to the same peer-review process as other submitted abstracts. No other competing interests were disclosed., (Copyright: © 2023 Harris NL et al.)
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- 2023
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25. The testicular microvasculature in Klinefelter syndrome is immature with compromised integrity and characterized by excessive inflammatory cross-talk.
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Johannsen EB, Skakkebæk A, Kalucka JM, Fedder J, Gravholt CH, and Just J
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- Male, Humans, Testis, Cross-Sectional Studies, Testosterone, Microvessels, Klinefelter Syndrome genetics, Klinefelter Syndrome complications, Oligospermia
- Abstract
Study Question: Does Klinefelter syndrome (KS) lead to a distinct gene expression pattern at single-cell level in the testes that could provide insight into the reported microvascular dysfunction in the testes?, Summary Answer: A distinct gene expression pattern within microvascular-associated cells of males with KS suggests excessive endothelial cell (EC) activation, disorganized vessel formation, and the presence of immature vessels with compromised integrity., What Is Known Already: Recent studies show that males with KS exhibit microvascular dysfunction in their testes, which affects blood flow and is associated with lower circulating levels of testosterone., Study Design, Size, Duration: A comparative cross-sectional study of males with KS (n = 6), non-obstructive azoospermia (NOA) (n = 5), cryptozoospermia (n = 3), and controls (n = 15) was carried out., Participants/materials, Setting, Methods: We analyzed publicly available single-cell RNA sequencing data of testicular cells from males with KS, males with NOA, males with cryptozoospermia, and controls. The integration of these datasets allowed us to analyze gene expression profiles and communication patterns among the cell types within the testis and to identify capillary ECs to investigate changes at the microvascular level., Main Results and the Role of Chance: Rooted in changes at the single-cell level, our study demonstrates a shift in gene expression forming the foundation for altered cellular communication, microvascular remodeling, and pro-inflammatory responses within the testes of males with KS. We identified genes that were dysregulated in capillary ECs from males with KS (Padj < 0.05). Specifically, the unique microvascular gene expression in males with KS indicated enhanced capillary EC activation and increased inflammatory cross-talk, leading to impaired vessel maturation and increased EC barrier permeability., Limitations, Reasons for Caution: Our study is constrained by an unbalanced design, with varying sample sizes and number of cells within each group. We acknowledge the restricted access to clinical information. In addition, our findings were deduced from changes in gene expression, which limits us to infer potential biological consequences arising from these alterations. Furthermore, the absence of a pre-pubertal age group limits the generalizability of our findings and warrants further investigation., Wider Implications of the Findings: This study offers novel insights into the testicular pathophysiology in KS and underscores the potential contribution of microvascular dysfunction to the hypogonadism and infertility observed in males with KS. While this study aims to better understand the microvascular dysfunction in KS, the precise connections to testosterone deficiency and testicular atrophy remain to be fully elucidated., Study Funding/competing Interest(s): A.S. was supported by the Independent Research Fund Denmark (0134-00130B). C.H.G. was supported by Novo Nordisk Foundation (NNF15OC0016474, NNF20OC0060610), 'Fonden til lægevidenskabens fremme', the Familien Hede Nielsen foundation and the Independent Research Fund Denmark (0134-00406A). E.B.J. was supported by Aarhus University and E.B.J. and C.H.G by the Independent Research Fund Denmark (2096-00165A). J.M.K. was supported by Lundbeckfonden (R307-2018-3667), Carlsberg Fonden (CF19-0687), Novo Nordisk Fonden (0073440) and Steno Diabetes Center Aarhus (SDCA). The authors declare no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)
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- 2023
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26. Seasonally increasing parasite load is associated with microbiome dysbiosis in wild bumblebees.
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Young MG, Just J, Lee YJ, McMahon T, Gonzalez J, Noh S, and Angelini DR
- Abstract
The microbiome is increasingly recognized for its complex relationship with host fitness. Bumblebees are host to a characteristic gut microbiome community that is derived and reinforced through social contact between individuals. The bumblebee microbiome is species-poor, and primarily composed from a small number of core taxa that are associated with the greater tribe of corbiculate bees. Experimental findings support a role for the core bumblebee microbiome in resistance to severe infections by a common trypanosomal parasite, Crithidia bombi . However, most studies have been small in scale, often considering just one or two bumblebee species, or making use of commercially-reared bees. To better understand the microbiome diversity of wild populations, we have deeply sampled field populations of ten sympatric species found throughout central and down east Maine in a three-year microbiome field survey. We have used 16S amplicon sequencing to produce microbiome community profiles, and qPCR to screen samples for infections by Crithidia bombi . The breadth of our dataset has enabled us to test for seasonal and interspecific trends in the microbiome community. Controlling for these external sources of variation, we have identified microbial factors associated with infection and parasite load that support the role of the core microbiome in resistance to severe infection.
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- 2023
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27. A Prospective Study of Lipids in Adult Women With Turner Syndrome.
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Sandahl KJ, Just J, Erlandsen M, Mortensen KH, Andersen NH, and Gravholt CH
- Abstract
Context: Turner syndrome (TS) is a rare genetic syndrome with an increased mortality, mainly attributed to cardiovascular disease., Objective: This work aimed to investigate and correlate the lipid profile in adult women with TS to clinical characteristics., Methods: A 12-year prospective cohort study, including 4 study visits, was conducted at a specialist hospital. A total of 102 women with TS qualified for inclusion. Excluding missing variables and participants lost to follow-up, 86 women (mean age 38.1 years; range, 18.4-62.1 years) were included in this study. Fifty-three women completed the study. Repeated-measurement analysis was performed, using total cholesterol (Total-C), low-density lipoprotein (LDL), triglycerides (TGs), and high-density lipoprotein (HDL) as outcome variables and age, karyotype, body mass index (BMI), treatment with statins, antidiabetics, and hormone replacement therapy as explanatory variables. Principal component analysis (PCA) and partial least squares (PLS) analysis were performed at the first study visit., Results: Hyperlipidemia was present in 30% of the TS cohort. Total-C increased with age (0.12 mmol/L/y; P = .016). LDL ( P = .08), TGs ( P = .14), and HDL ( P = .24) were not associated with age. BMI significantly increased total-C (0.19 mmol/L/kg/m
2 ; P = .006), LDL (0.63 mmol/L/kg/m2 ; P < .001), and TGs (0.80 mmol/L/kg/m2 ; P < .001) and decreased HDL (-0.59 mmol/L/kg/m2 ; P < .001). PCA and PLS analysis found correlations between weight and BMI and total-C, LDL, and TGs., Conclusion: Hyperlipidemia is more prevalent in adult women with TS across adulthood compared to the background population. Total-C, LDL, TGs, and HDL were significantly associated with BMI characterizing the atherogenic profile in adult women with TS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)- Published
- 2023
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28. Can a Targeted Social Media Campaign Increase Reach of, and Engagement With, Heart Failure Self-Management Resources in Culturally and Linguistically Diverse Communities in Victoria, Australia? An Evaluation Including Cost.
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Matthews S, Just J, Jennings G, Bray J, Lewis J, and Buttery A
- Abstract
Aim: This study investigates whether a targeted social media campaign increases reach and engagement of heart failure self-management educational resources among culturally and linguistically diverse communities in Victoria, Australia., Methods: A targeted six-week Facebook social media campaign (from 3 October 2022 to 13 November 2022) was performed using the Precision Public Health Framework. Animated heart failure educational videos were developed, translated, and publicised among Mandarin-, Vietnamese- and English-speaking communities in Victoria, Australia. Data from Facebook, Google Analytics and social marketing costs were analysed. An independent, two sample t-test was applied to investigate differences in the performance (views and cost-per-click) of the English and translated Mandarin and Vietnamese social media campaigns. Webpage views (of the promoted heart failure webpage) during the campaign were compared to the same period 12 months prior., Results: A total of 664,434 English and 182,294 translated Vietnamese and Mandarin video advertisements were placed and seen in individuals' social media feeds (impressions) over the six weeks. Per capita reach was proportionally higher for Vietnamese and Mandarin video advertisements (54% versus 15%). The percentage of those who watched the educational video in the social media posts, for at least 15 seconds (a 'ThruPlay'), was significantly higher in Mandarin and Vietnamese-speaking communities (75% versus 40% among the English-speaking community p<0.0001). However, those viewing in English had significantly longer engagement and watched at least half of the video (2.5% versus Vietnamese and Mandarin viewers (0.31%), p<0.0001). The click-through rate and cost-per-click were significantly higher for the translated social media posts compared with the English (0.77% vs 0.62%, p=0.0185 and AUD$4.48 vs AUD$3.22, p<0.0001)., Conclusion: A targeted six-week Facebook social media campaign using translated video animations in Vietnamese and Mandarin had significantly higher reach, initial views (first 15 seconds) and higher click-through rates, but fewer views of at least half of the video, compared with the Facebook English videos. Higher costs-per-click were associated with the translated campaign. Further research is needed to understand the extent that social media translated campaigns can influence health behaviour., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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29. T-cell derived extracellular vesicles prime macrophages for improved STING based cancer immunotherapy.
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Hansen AS, Jensen LS, Gammelgaard KR, Ryttersgaard KG, Krapp C, Just J, Jønsson KL, Jensen PB, Boesen T, Johansen M, Etzerodt A, Deleuran BW, and Jakobsen MR
- Subjects
- Humans, T-Lymphocytes, Interferons genetics, Interferons metabolism, Immunotherapy, Macrophages metabolism, Tumor Microenvironment, Extracellular Vesicles metabolism, Neoplasms metabolism
- Abstract
A key phenomenon in cancer is the establishment of a highly immunosuppressive tumour microenvironment (TME). Despite advances in immunotherapy, where the purpose is to induce tumour recognition and hence hereof tumour eradication, the majority of patients applicable for such treatment still fail to respond. It has been suggested that high immunological activity in the tumour is essential for achieving effective response to immunotherapy, which therefore have led to exploration of strategies that triggers inflammatory pathways. Here activation of the stimulator of interferon genes (STING) signalling pathway has been considered an attractive target, as it is a potent trigger of pro-inflammatory cytokines and types I and III interferons. However, immunotherapy combined with targeted STING agonists has not yielded sustained clinical remission in humans. This suggests a need for exploring novel adjuvants to improve the innate immunological efficacy. Here, we demonstrate that extracellular vesicles (EVs), derived from activated CD4
+ T cells (T-EVs), sensitizes macrophages to elevate STING activation, mediated by IFNγ carried on the T-EVs. Our work support that T-EVs can disrupt the immune suppressive environment in the tumour by reprogramming macrophages to a pro-inflammatory phenotype, and priming them for a robust immune response towards STING activation., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)- Published
- 2023
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30. The multi-omic landscape of sex chromosome abnormalities: current status and future directions.
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Tallaksen HBL, Johannsen EB, Just J, Viuff MH, Gravholt CH, and Skakkebæk A
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Sex chromosome abnormalities (SCAs) are chromosomal disorders with either a complete or partial loss or gain of sex chromosomes. The most frequent SCAs include Turner syndrome (45,X), Klinefelter syndrome (47,XXY), Trisomy X syndrome (47,XXX), and Double Y syndrome (47,XYY). The phenotype seen in SCAs is highly variable and may not merely be due to the direct genomic imbalance from altered sex chromosome gene dosage but also due to additive alterations in gene networks and regulatory pathways across the genome as well as individual genetic modifiers. This review summarizes the current insight into the genomics of SCAs. In addition, future directions of research that can contribute to decipher the genomics of SCA are discussed such as single-cell omics, spatial transcriptomics, system biology thinking, human-induced pluripotent stem cells, and animal models, and how these data may be combined to bridge the gap between genomics and the clinical phenotype.
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- 2023
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31. Dosage of the pseudoautosomal gene SLC25A6 is implicated in QTc interval duration.
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Skakkebæk A, Kjær-Sørensen K, Matchkov VV, Christensen LL, Just J, Cömert C, Andersen NH, Oxvig C, and Gravholt CH
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- Animals, Female, Humans, Male, Adenosine Triphosphate, Electrocardiography, X Chromosome, Zebrafish genetics, Adenine Nucleotide Translocator 3, Klinefelter Syndrome, Long QT Syndrome genetics, Turner Syndrome
- Abstract
The genetic architecture of the QT interval, defined as the period from onset of depolarisation to completion of repolarisation of the ventricular myocardium, is incompletely understood. Only a minor part of the QT interval variation in the general population has been linked to autosomal variant loci. Altered X chromosome dosage in humans, as seen in sex chromosome aneuploidies such as Turner syndrome (TS) and Klinefelter syndrome (KS), is associated with altered QTc interval (heart rate corrected QT), indicating that genes, located in the pseudoautosomal region 1 of the X and Y chromosomes may contribute to QT interval variation. We investigate the dosage effect of the pseudoautosomal gene SLC25A6, encoding the membrane ADP/ATP translocase 3 in the inner mitochondrial membrane, on QTc interval duration. To this end we used human participants and in vivo zebrafish models. Analyses in humans, based on 44 patients with KS, 44 patients with TS, 59 male and 22 females, revealed a significant negative correlation between SLC25A6 expression level and QTc interval duration. Similarly, downregulation of slc25a6 in zebrafish increased QTc interval duration with pharmacological inhibition of K
ATP channels restoring the systolic duration, whereas overexpression of SLC25A6 shortened QTc, which was normalized by pharmacological activation of KATP channels. Our study demonstrate an inverse relationship between SLC25A6 dosage and QTc interval indicating that SLC25A6 contributes to QT interval variation., (© 2023. The Author(s).)- Published
- 2023
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32. Omalizumab for the treatment of patients with severe allergic asthma with immunoglobulin E levels above >1500 IU/mL.
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Menzella F, Just J, Sauerbeck IS, Mailaender C, Saccheri F, Thonnelier C, Jaumont X, and Mala L
- Abstract
Immunoglobulin E (IgE) plays a critical role in the allergen-initiated inflammatory pathway and thus serves as a viable therapeutic target in allergic or IgE-mediated diseases such as asthma. Omalizumab, an anti -IgE biologic, has been approved in the United States (US, 2003) and in the European Union (EU, 2005) as an add-on therapy in patients with moderate-to-severe persistent asthma and severe allergic asthma (SAA) aged 6 years and older. The dose and frequency of omalizumab are adjusted based on the patient's body weight and baseline IgE levels, as recommended by its dosing tables. Currently, these dosing recommendations are limited to patients with baseline IgE levels of up to 1500 IU/mL in the European Union and 700 IU/mL in the United States. However, many patients with SAA have IgE levels >1500 IU/mL, highlighting an unmet need. This review presents the current evidence on the treatment benefits of omalizumab in patients with IgE levels >1500 IU/mL. The findings from the reviewed studies which included >3000 patients support the efficacy and effectiveness of omalizumab in reducing exacerbations, and improving asthma control, lung function, and quality of life in patients with severe asthma having IgE levels beyond the current dosing range. Omalizumab was well-tolerated in these patients, with no new safety signals. In addition, high IgE levels (>1500 IU/mL) are also reported in several comorbidities of asthma (allergic rhinitis, atopic dermatitis, allergic bronchopulmonary aspergillosis [ABPA], food allergy, and nasal polyposis) and omalizumab has demonstrated efficacy and safety in these indications. These data suggest that omalizumab may be considered for administration in SAA patients, with high IgE levels outside the current dosing tables. A detailed assessment of patients with high IgE levels is needed before deciding on the optimal treatment approach. A management algorithm for SAA patients with IgE >1500 IU/mL is proposed in this review and a suggestion to follow the Delphi consensus is advised., (© 2023 Novartis Pharma AG, Basel.)
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- 2023
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33. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.
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Bousquet J, Melén E, Haahtela T, Koppelman GH, Togias A, Valenta R, Akdis CA, Czarlewski W, Rothenberg M, Valiulis A, Wickman M, Akdis M, Aguilar D, Bedbrook A, Bindslev-Jensen C, Bosnic-Anticevich S, Boulet LP, Brightling CE, Brussino L, Burte E, Bustamante M, Canonica GW, Cecchi L, Celedon JC, Chaves Loureiro C, Costa E, Cruz AA, Erhola M, Gemicioglu B, Fokkens WJ, Garcia-Aymerich J, Guerra S, Heinrich J, Ivancevich JC, Keil T, Klimek L, Kuna P, Kupczyk M, Kvedariene V, Larenas-Linnemann DE, Lemonnier N, Lodrup Carlsen KC, Louis R, Makela M, Makris M, Maurer M, Momas I, Morais-Almeida M, Mullol J, Naclerio RN, Nadeau K, Nadif R, Niedoszytko M, Okamoto Y, Ollert M, Papadopoulos NG, Passalacqua G, Patella V, Pawankar R, Pham-Thi N, Pfaar O, Regateiro FS, Ring J, Rouadi PW, Samolinski B, Sastre J, Savouré M, Scichilone N, Shamji MH, Sheikh A, Siroux V, Sousa-Pinto B, Standl M, Sunyer J, Taborda-Barata L, Toppila-Salmi S, Torres MJ, Tsiligianni I, Valovirta E, Vandenplas O, Ventura MT, Weiss S, Yorgancioglu A, Zhang L, Abdul Latiff AH, Aberer W, Agache I, Al-Ahmad M, Alobid I, Ansotegui IJ, Arshad SH, Asayag E, Barbara C, Baharudin A, Battur L, Bennoor KS, Berghea EC, Bergmann KC, Bernstein D, Bewick M, Blain H, Bonini M, Braido F, Buhl R, Bumbacea RS, Bush A, Calderon M, Calvo-Gil M, Camargos P, Caraballo L, Cardona V, Carr W, Carreiro-Martins P, Casale T, Cepeda Sarabia AM, Chandrasekharan R, Charpin D, Chen YZ, Cherrez-Ojeda I, Chivato T, Chkhartishvili E, Christoff G, Chu DK, Cingi C, Correia de Sousa J, Corrigan C, Custovic A, D'Amato G, Del Giacco S, De Blay F, Devillier P, Didier A, do Ceu Teixeira M, Dokic D, Douagui H, Doulaptsi M, Durham S, Dykewicz M, Eiwegger T, El-Sayed ZA, Emuzyte R, Fiocchi A, Fyhrquist N, Gomez RM, Gotua M, Guzman MA, Hagemann J, Hamamah S, Halken S, Halpin DMG, Hofmann M, Hossny E, Hrubiško M, Irani C, Ispayeva Z, Jares E, Jartti T, Jassem E, Julge K, Just J, Jutel M, Kaidashev I, Kalayci O, Kalyoncu AF, Kardas P, Kirenga B, Kraxner H, Kull I, Kulus M, La Grutta S, Lau S, Le Tuyet Thi L, Levin M, Lipworth B, Lourenço O, Mahboub B, Martinez-Infante E, Matricardi P, Miculinic N, Migueres N, Mihaltan F, Mohammad Y, Moniuszko M, Montefort S, Neffen H, Nekam K, Nunes E, Nyembue Tshipukane D, O'Hehir R, Ogulur I, Ohta K, Okubo K, Ouedraogo S, Olze H, Pali-Schöll I, Palomares O, Palosuo K, Panaitescu C, Panzner P, Park HS, Pitsios C, Plavec D, Popov TA, Puggioni F, Quirce S, Recto M, Repka-Ramirez MS, Robalo Cordeiro C, Roche N, Rodriguez-Gonzalez M, Romantowski J, Rosario Filho N, Rottem M, Sagara H, Serpa FS, Sayah Z, Scheire S, Schmid-Grendelmeier P, Sisul JC, Sole D, Soto-Martinez M, Sova M, Sperl A, Spranger O, Stelmach R, Suppli Ulrik C, Thomas M, To T, Todo-Bom A, Tomazic PV, Urrutia-Pereira M, Valentin-Rostan M, Van Ganse E, van Hage M, Vasankari T, Vichyanond P, Viegi G, Wallace D, Wang DY, Williams S, Worm M, Yiallouros P, Yusuf O, Zaitoun F, Zernotti M, Zidarn M, Zuberbier J, Fonseca JA, Zuberbier T, and Anto JM
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- Humans, Allergens, Multimorbidity, Rhinitis diagnosis, Rhinitis epidemiology, Rhinitis complications, Asthma diagnosis, Asthma epidemiology, Asthma etiology, Rhinitis, Allergic complications
- Abstract
Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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- 2023
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34. X chromosome dosage and the genetic impact across human tissues.
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Viuff M, Skakkebæk A, Johannsen EB, Chang S, Pedersen SB, Lauritsen KM, Pedersen MGB, Trolle C, Just J, and Gravholt CH
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- Humans, Y Chromosome, Phenotype, Aneuploidy, GTP-Binding Proteins, Transcription Factors, X Chromosome, Sex Chromosome Aberrations
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Background: Sex chromosome aneuploidies (SCAs) give rise to a broad range of phenotypic traits and diseases. Previous studies based on peripheral blood samples have suggested the presence of ripple effects, caused by altered X chromosome number, affecting the methylome and transcriptome. Whether these alterations can be connected to disease-specific tissues, and thereby having clinical implication for the phenotype, remains to be elucidated., Methods: We performed a comprehensive analysis of X chromosome number on the transcriptome and methylome in blood, fat, and muscle tissue from individuals with 45,X, 46,XX, 46,XY, and 47,XXY., Results: X chromosome number affected the transcriptome and methylome globally across all chromosomes in a tissue-specific manner. Furthermore, 45,X and 47,XXY demonstrated a divergent pattern of gene expression and methylation, with overall gene downregulation and hypomethylation in 45,X and gene upregulation and hypermethylation in 47,XXY. In fat and muscle, a pronounced effect of sex was observed. We identified X chromosomal genes with an expression pattern different from what would be expected based on the number of X and Y chromosomes. Our data also indicate a regulatory function of Y chromosomal genes on X chromosomal genes. Fourteen X chromosomal genes were downregulated in 45,X and upregulated in 47,XXY, respectively, in all three tissues (AKAP17A, CD99, DHRSX, EIF2S3, GTPBP6, JPX, KDM6A, PP2R3B, PUDP, SLC25A6, TSIX, XIST, ZBED1, ZFX). These genes may be central in the epigenetic and genomic regulation of sex chromosome aneuploidies., Conclusion: We highlight a tissue-specific and complex effect of X chromosome number on the transcriptome and methylome, elucidating both shared and non-shared gene-regulatory mechanism between SCAs., (© 2023. The Author(s).)
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- 2023
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35. Theme and variation in the evolution of insect sex determination.
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Laslo M, Just J, and Angelini DR
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- Male, Female, Animals, Phylogeny, RNA Interference, Amino Acid Sequence, Sex Determination Processes genetics, Genes, Insect, Insect Proteins genetics, Insect Proteins metabolism, Insecta genetics, Heteroptera genetics
- Abstract
The development of dimorphic adult sexes is a critical process for most animals, one that is subject to intense selection. Work in vertebrate and insect model species has revealed that sex determination mechanisms vary widely among animal groups. However, this variation is not uniform, with a limited number of conserved factors. Therefore, sex determination offers an excellent context to consider themes and variations in gene network evolution. Here we review the literature describing sex determination in diverse insects. We have screened public genomic sequence databases for orthologs and duplicates of 25 genes involved in insect sex determination, identifying patterns of presence and absence. These genes and a 3.5 reference set of 43 others were used to infer phylogenies and compared to accepted organismal relationships to examine patterns of congruence and divergence. The function of candidate genes for roles in sex determination (virilizer, female-lethal-2-d, transformer-2) and sex chromosome dosage compensation (male specific lethal-1, msl-2, msl-3) were tested using RNA interference in the milkweed bug, Oncopeltus fasciatus. None of these candidate genes exhibited conserved roles in these processes. Amidst this variation we wish to highlight the following themes for the evolution of sex determination: (1) Unique features within taxa influence network evolution. (2) Their position in the network influences a component's evolution. Our analyses also suggest an inverse association of protein sequence conservation with functional conservation., (© 2022 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals LLC.)
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- 2023
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36. Distinct developmental mechanisms influence sexual dimorphisms in the milkweed bug Oncopeltus fasciatus .
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Just J, Laslo M, Lee YJ, Yarnell M, Zhang Z, and Angelini DR
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- Animals, Female, Male, Cell Nucleus, DNA-Binding Proteins, Genitalia, Nerve Tissue Proteins, Transcription Factors, Heteroptera genetics, Sex Characteristics
- Abstract
Sexual dimorphism is common in animals. The most complete model of sex determination comes from Drosophila melanogaster , where the relative dosage of autosomes and X chromosomes leads indirectly to sex-specific transcripts of doublesex ( dsx ). Female Dsx interacts with a mediator complex protein encoded by intersex ( ix ) to activate female development. In males, the transcription factor encoded by fruitless ( fru ) promotes male-specific behaviour. The genetics of sex determination have been examined in a small number of other insects, yet several questions remain about the plesiomorphic state. Is dsx required for female and male development? Is fru conserved in male behaviour or morphology? Are other components such as ix functionally conserved? To address these questions, we report expression and functional tests of dsx , ix and fru in the hemipteran Oncopeltus fasciatus , characterizing three sexual dimorphisms. dsx prevents ix phenotypes in all sexes and dimorphic traits in the milkweed bug. ix and fru are expressed across the body, in females and males. fru and ix also affect the genitalia of both sexes, but have effects limited to different dimorphic structures in different sexes. These results reveal roles for i x and fru distinct from other insects, and demonstrate distinct development mechanisms in different sexually dimorphic structures.
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- 2023
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37. Staphylococcal Sensitization: A Correlate of Type 2-High Inflammation in Children With Severe Asthma.
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Bourgoin-Heck M, Duféal M, Saf S, Rancière F, Chantran Y, Momas I, Wanin S, Saint-Pierre P, and Just J
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- Humans, Child, Child, Preschool, Prospective Studies, Cross-Sectional Studies, Staphylococcus aureus, Enterotoxins, Staphylococcus, Inflammation, Immunoglobulin E, Asthma epidemiology, Asthma complications
- Abstract
Background: Sensitization to Staphylococcus aureus enterotoxin (SE) has been identified to be a risk factor for asthma, but its determinants remain unclear., Objective: To determine the significance of SE sensitization in children with moderate to severe asthma., Methods: This was an observational cross-sectional analysis performed from 2011 to 2015 including children from the prospective Severe Asthma Molecular Phenotype cohort: school-age children with severe and moderate asthma or preschool-age children with severe and moderate recurrent wheeze. We evaluated sensitization to four SEs (Staphylococcus enterotoxin A, Staphylococcus enterotoxin B, Staphylococcus enterotoxin C, and toxic shock staphylococcic toxin)., Results: We analyzed data from 377 children: 233 of preschool age and 144 of school age. Among them, 26 (11.2%) and 59 (41.0%) children, respectively, had sensitization to at least one SE. The burden of sensitization was higher in older children in terms of both specific IgE levels and the number of sensitizations. In multivariable analysis, SE sensitization was associated with elevated total IgE in both populations (odds ratio [OR] = 9.35, P = .01; and OR = 8.06, P < .01), and with bronchoalveolar lavage eosinophilia in both preschool and school-age children (OR = 3.95, P = .03; and OR = 4.11, P = .03, respectively). Classification and regression trees showed an association of SE sensitization with age and with total IgE in the entire population, and with total IgE, bronchoalveolar lavage eosinophilia, and blood eosinophilia in school-age children., Conclusions: Staphylococcal enterotoxin sensitization was correlated with type 2-high inflammation (eosinophilic inflammation and elevated total IgE count) in this population of moderate to severe asthmatic children., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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38. APPsα rescues CDK5 and GSK3β dysregulation and restores normal spine density in Tau transgenic mice.
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Baltissen D, Bold CS, Rehra L, Banićević M, Fricke J, Just J, Ludewig S, Buchholz CJ, Korte M, and Müller UC
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The Tau protein can be phosphorylated by numerous kinases. In Alzheimer's disease (AD) hyperphosphorylated Tau species accumulate as neurofibrillary tangles that constitute a major hallmark of AD. AD is further characterized by extracellular Aβ plaques, derived from the β-amyloid precursor protein APP. Whereas Aβ is produced by amyloidogenic APP processing, APP processing along the competing non-amyloidogenic pathway results in the secretion of neurotrophic and synaptotrophic APPsα. Recently, we demonstrated that APPsα has therapeutic effects in transgenic AD model mice and rescues Aβ-dependent impairments. Here, we examined the potential of APPsα to regulate two major Tau kinases, GSK3β and CDK5 in THY-Tau22 mice, a widely used mouse model of tauopathy. Immunohistochemistry revealed a dramatic increase in pathologically phosphorylated (AT8 and AT180) or misfolded Tau species (MC1) in the hippocampus of THY-Tau22 mice between 3 and 12 months of age. Using a highly sensitive radioactive kinase assay with recombinant human Tau as a substrate and immunoblotting, we demonstrate an increase in GSK3β and CDK5 activity in the hippocampus of THY-Tau22 mice. Interestingly, AAV-mediated intracranial expression of APPsα in THY-Tau22 mice efficiently restored normal GSK3β and CDK5 activity. Western blot analysis revealed upregulation of the CDK5 regulatory proteins p35 and p25, indicating CDK5 hyperactivation in THY-Tau22 mice. Strikingly, AAV-APPsα rescued p25 upregulation to wild-type levels even at stages of advanced Tau pathology. Sarkosyl fractionation used to study the abundance of soluble and insoluble phospho-Tau species revealed increased soluble AT8-Tau and decreased insoluble AT100-Tau species upon AAV-APPsα injection. Moreover, AAV-APPsα reduced misfolded (MC1) Tau species, particularly in somatodendritic compartments of CA1 pyramidal neurons. Finally, we show that AAV-APPsα upregulated PSD95 expression and rescued deficits in spine density of THY-Tau22 mice. Together our findings suggest that APPsα holds therapeutic potential to mitigate Tau-induced pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baltissen, Bold, Rehra, Banićević, Fricke, Just, Ludewig, Buchholz, Korte and Müller.)
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- 2023
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39. The Changing Face of Turner Syndrome.
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Gravholt CH, Viuff M, Just J, Sandahl K, Brun S, van der Velden J, Andersen NH, and Skakkebaek A
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- Female, Humans, Diabetes Mellitus, Type 2 complications, Endocrine System Diseases, Infertility, Turner Syndrome diagnosis, Turner Syndrome genetics, Turner Syndrome complications
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Turner syndrome (TS) is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated with a wide range of clinical stigmata, such as short stature, ovarian dysgenesis, delayed puberty and infertility, congenital malformations, endocrine disorders, including a range of autoimmune conditions and type 2 diabetes, and neurocognitive deficits. Morbidity and mortality are clearly increased compared with the general population and the average age at diagnosis is quite delayed. During recent years it has become clear that a multidisciplinary approach is necessary toward the patient with TS. A number of clinical advances has been implemented, and these are reviewed. Our understanding of the genomic architecture of TS is advancing rapidly, and these latest developments are reviewed and discussed. Several candidate genes, genomic pathways and mechanisms, including an altered transcriptome and epigenome, are also presented., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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40. Evaluating the Representation of Community Colleges in Biology Education Research Publications following a Call to Action.
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Creech C, Just J, Hammarlund S, Rolle CE, Gonsar NY, Olson A, Campbell N, Mennes K, Adoradio C, Soneral P, Ewell S, Mazur C, Lane AK, Hewlett J, and Cotner S
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- Biology education, Humans, Learning, Universities, Faculty, Students
- Abstract
Interest in biology education research (BER) has been growing over the last two decades, yet few BER publications focus on community colleges, which serve a large percentage of the undergraduate student population and a majority of those students who identify with historically underserved groups. In this paper, we define community college biology education research (CC BER) as publications with a community college faculty member as an author, publications with a community college study context or a focus on community college biology teaching and learning, and publications that use community college students as a source of data. We conducted a literature review to quantify how CC BER has progressed since initial calls for broadening participation by recording the number of CC BER publications in seven prominent journals between 2016 and 2020. Our formal analysis of peer-reviewed BER literature indicates that there has been a statistically significant increase in CC BER publications from 3.2% to 5.9% of total BER publications since the last analysis in 2017. We conclude with a discussion of strategies for further broadening of participation in CC BER.
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- 2022
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41. Evaluation of genome and base editing tools in maize protoplasts.
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Fierlej Y, Jacquier NMA, Guille L, Just J, Montes E, Richard C, Loue-Manifel J, Depège-Fargeix N, Gaillard A, Widiez T, and Rogowsky PM
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Introduction: Despite its rapid worldwide adoption as an efficient mutagenesis tool, plant genome editing remains a labor-intensive process requiring often several months of in vitro culture to obtain mutant plantlets. To avoid a waste in time and money and to test, in only a few days, the efficiency of molecular constructs or novel Cas9 variants (clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9) prior to stable transformation, rapid analysis tools are helpful., Methods: To this end, a streamlined maize protoplast system for transient expression of CRISPR/Cas9 tools coupled to NGS (next generation sequencing) analysis and a novel bioinformatics pipeline was established., Results and Discussion: Mutation types found with high frequency in maize leaf protoplasts had a trend to be the ones observed after stable transformation of immature maize embryos. The protoplast system also allowed to conclude that modifications of the sgRNA (single guide RNA) scaffold leave little room for improvement, that relaxed PAM (protospacer adjacent motif) sites increase the choice of target sites for genome editing, albeit with decreased frequency, and that efficient base editing in maize could be achieved for certain but not all target sites. Phenotypic analysis of base edited mutant maize plants demonstrated that the introduction of a stop codon but not the mutation of a serine predicted to be phosphorylated in the bHLH (basic helix loop helix) transcription factor ZmICEa (INDUCER OF CBF EXPRESSIONa) caused abnormal stomata, pale leaves and eventual plant death two months after sowing., Competing Interests: YF and AG were employed by MAS Seeds, NMAJ is presently employed by Limagrain Europe, TW has currently a collaborative research project with Limagrain Europe, and PR is a member of the operational directorate of the PlantAlliance consortium. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fierlej, Jacquier, Guille, Just, Montes, Richard, Loue-Manifel, Depège-Fargeix, Gaillard, Widiez and Rogowsky.)
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- 2022
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42. Epigenetic and transcriptomic alterations in offspring born to women with type 1 diabetes (the EPICOM study).
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Knorr S, Skakkebæk A, Just J, Johannsen EB, Trolle C, Vang S, Lohse Z, Bytoft B, Damm P, Højlund K, Jensen DM, and Gravholt CH
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- Adolescent, Carbohydrates, DNA Methylation genetics, Epigenesis, Genetic, Female, Follow-Up Studies, Glucose, Humans, RNA, Transcriptome, Diabetes Mellitus, Type 1 genetics
- Abstract
Background: Offspring born to women with pregestational type 1 diabetes (T1DM) are exposed to an intrauterine hyperglycemic milieu and has an increased risk of metabolic disease later in life. In this present study, we hypothesize that in utero exposure to T1DM alters offspring DNA methylation and gene expression, thereby altering their risk of future disease., Methods: Follow-up study using data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) collected between 2012 and 2013., Setting: Exploratory sub-study using data from the nationwide EPICOM study., Participants: Adolescent offspring born to women with T1DM (n=20) and controls (n=20) matched on age, sex, and postal code., Main Outcome Measures: This study investigates DNA methylation using the 450K-Illumina Infinium assay and RNA expression (RNA sequencing) of leucocytes from peripheral blood samples., Results: We identified 9 hypomethylated and 5 hypermethylated positions (p < 0.005, |ΔM-value| > 1) and 38 up- and 1 downregulated genes (p < 0.005, log2FC ≥ 0.3) in adolescent offspring born to women with T1DM compared to controls. None of these findings remained significant after correction for multiple testing. However, we identified differences in gene co-expression networks, which could be of biological significance, using weighted gene correlation network analysis. Interestingly, one of these modules was significantly associated with offspring born to women with T1DM. Functional enrichment analysis, using the identified changes in methylation and gene expression as input, revealed enrichment in disease ontologies related to diabetes, carbohydrate and glucose metabolism, pathways including MAPK1/MAPK3 and MAPK family signaling, and genes related to T1DM, obesity, atherosclerosis, and vascular pathologies. Lastly, by integrating the DNA methylation and RNA expression data, we identified six genes where relevant methylation changes corresponded with RNA expression (CIITA, TPM1, PXN, ST8SIA1, LIPA, DAXX)., Conclusions: These findings suggest the possibility for intrauterine exposure to maternal T1DM to impact later in life methylation and gene expression in the offspring, a profile that may be linked to the increased risk of vascular and metabolic disease later in life., (© 2022. The Author(s).)
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- 2022
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43. Sex chromosome aneuploidies give rise to changes in the circular RNA profile: A circular transcriptome-wide study of Turner and Klinefelter syndrome across different tissues.
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Johannsen EB, Just J, Viuff MH, Okholm TLH, Pedersen SB, Meyer Lauritsen K, Trolle C, Pedersen MGB, Chang S, Fedder J, Skakkebæk A, and Gravholt CH
- Abstract
Purpose: The landscape of circular RNAs (circRNAs), an important class of non-coding RNAs that regulate gene expression, has never been described in human disorders of sex chromosome aneuploidies. We profiled circRNAs in Turner syndrome females (45,X; TS) and Klinefelter syndrome males (47,XXY; KS) to investigate how circRNAs respond to a missing or an extra X chromosome. Methods: Samples of blood, muscle and fat were collected from individuals with TS ( n = 33) and KS ( n = 22) and from male ( n = 16) and female ( n = 44) controls. CircRNAs were identified using a combination of circRNA identification pipelines (CIRI2, CIRCexplorer2 and circRNA_finder). Results: Differential expression of circRNAs was observed throughout the genome in TS and KS, in all tissues. The host-genes from which several of these circRNAs were derived, were associated with known phenotypic traits. Furthermore, several differentially expressed circRNAs had the potential to capture micro RNAs that targeted protein-coding genes with altered expression in TS and KS. Conclusion: Sex chromosome aneuploidies introduce changes in the circRNA transcriptome, demonstrating that the genomic changes in these syndromes are more complex than hitherto thought. CircRNAs may help explain some of the genomic and phenotypic traits observed in these syndromes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Johannsen, Just, Viuff, Okholm, Pedersen, Meyer Lauritsen, Trolle, Pedersen, Chang, Fedder, Skakkebæk and Gravholt.)
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- 2022
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44. APPsα Rescues Tau-Induced Synaptic Pathology.
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Bold CS, Baltissen D, Ludewig S, Back MK, Just J, Kilian L, Erdinger S, Banicevic M, Rehra L, Almouhanna F, Nigri M, Wolfer DP, Spilger R, Rohr K, Kann O, Buchholz CJ, von Engelhardt J, Korte M, and Müller UC
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- Animals, Female, Hippocampus metabolism, Male, Mice, Mice, Transgenic, Neuronal Plasticity physiology, Alzheimer Disease metabolism, Tauopathies pathology
- Abstract
Alzheimer's disease (AD) is histopathologically characterized by Aβ plaques and the accumulation of hyperphosphorylated Tau species, the latter also constituting key hallmarks of primary tauopathies. Whereas Aβ is produced by amyloidogenic APP processing, APP processing along the competing nonamyloidogenic pathway results in the secretion of neurotrophic and synaptotrophic APPsα. Recently, we demonstrated that APPsα has therapeutic effects in transgenic AD model mice and rescues Aβ-dependent impairments. Here, we examined the potential of APPsα to mitigate Tau-induced synaptic deficits in P301S mice (both sexes), a widely used mouse model of tauopathy. Analysis of synaptic plasticity revealed an aberrantly increased LTP in P301S mice that could be normalized by acute application of nanomolar amounts of APPsα to hippocampal slices, indicating a homeostatic function of APPsα on a rapid time scale. Further, AAV-mediated in vivo expression of APPsα restored normal spine density of CA1 neurons even at stages of advanced Tau pathology not only in P301S mice, but also in independent THY-Tau22 mice. Strikingly, when searching for the mechanism underlying aberrantly increased LTP in P301S mice, we identified an early and progressive loss of major GABAergic interneuron subtypes in the hippocampus of P301S mice, which may lead to reduced GABAergic inhibition of principal cells. Interneuron loss was paralleled by deficits in nest building, an innate behavior highly sensitive to hippocampal impairments. Together, our findings indicate that APPsα has therapeutic potential for Tau-mediated synaptic dysfunction and suggest that loss of interneurons leads to disturbed neuronal circuits that compromise synaptic plasticity as well as behavior. SIGNIFICANCE STATEMENT Our findings indicate, for the first time, that APPsα has the potential to rescue Tau-induced spine loss and abnormal synaptic plasticity. Thus, APPsα might have therapeutic potential not only because of its synaptotrophic functions, but also its homeostatic capacity for neuronal network activity. Hence, APPsα is one of the few molecules which has proven therapeutic effects in mice, both for Aβ- and Tau-dependent synaptic impairments and might therefore have therapeutic potential for patients suffering from AD or primary tauopathies. Furthermore, we found in P301S mice a pronounced reduction of inhibitory interneurons as the earliest pathologic event preceding the accumulation of hyperphosphorylated Tau species. This loss of interneurons most likely disturbs neuronal circuits that are important for synaptic plasticity and behavior., (Copyright © 2022 the authors.)
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- 2022
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45. Transcriptional reprogramming during floral fate acquisition.
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Larrieu A, Brunoud G, Guérault A, Lainé S, Hennet L, Stigliani A, Gildea I, Just J, Soubigou-Taconnat L, Balzergue S, Davies B, Scarpella E, Helariutta Y, Parcy F, and Vernoux T
- Abstract
Coordinating growth and patterning is essential for eukaryote morphogenesis. In plants, auxin is a key regulator of morphogenesis implicated throughout development. Despite this central role, our understanding of how auxin coordinates cell fate and growth changes is still limited. Here, we addressed this question using a combination of genomic screens to delve into the transcriptional network induced by auxin at the earliest stage of flower development, prior to morphological changes. We identify a shoot-specific network suggesting that auxin initiates growth through an antagonistic regulation of growth-promoting and growth-repressive hormones, quasi-synchronously to floral fate specification. We further identify two DNA-binding One Zinc Finger (DOF) transcription factors acting in an auxin-dependent network that could interface growth and cell fate from the early stages of flower development onward., Competing Interests: The authors declare that they have no competing interest., (© 2022 The Authors.)
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- 2022
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46. Women With Turner Syndrome Are Both Estrogen and Androgen Deficient: The Impact of Hormone Replacement Therapy.
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Viuff MH, Just J, Brun S, Dam TV, Hansen M, Melgaard L, Hougaard DM, Lappe M, and Gravholt CH
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- Estradiol, Female, Follicle Stimulating Hormone, Gonadal Steroid Hormones therapeutic use, Humans, Luteinizing Hormone, Progesterone therapeutic use, Sex Hormone-Binding Globulin analysis, Testosterone, Androgens deficiency, Estrogens deficiency, Hormone Replacement Therapy, Turner Syndrome drug therapy
- Abstract
Context: Women with Turner syndrome (TS) suffer from hypergonadotropic hypogonadism, causing a deficit in gonadal hormone secretion. As a consequence, these women are treated with estrogen from the age of 12 years, and later in combination with progesterone. However, androgens have been given less attention., Objective: To assess sex hormone levels in women with TS, both those treated and those nontreated with hormone replacement therapy (HRT), and investigate the impact of HRT on sex hormone levels., Methods: At Aarhus University Hospital, 99 women with TS were followed 3 times from August 2003 to February 2010. Seventeen were lost during follow-up. Control group 1 consisted of 68 healthy age-matched control women seen once during this period. Control group 2 consisted of 28 young, eumenorrheic women sampled 9 times throughout the same menstrual cycle. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol, estrone sulfate, DHEAS, testosterone, free androgen index, androstenedione, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were analyzed., Results: All androgens, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were 30% to 50% lower in TS compared with controls (P < 0.01). FSH, LH, and estrone sulfate were more than doubled in women with TS compared with controls (P < 0.02). Using principal component analysis, we describe a positive correlation between women with TS receiving HRT, elevated levels of SHBG, and decreased levels of androgens., Conclusion: The sex hormone profile in TS reveals a picture of androgen deficiency, aggravated further by HRT. Conventional HRT does not normalize estradiol levels in TS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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47. Persistent influence of precession on northern ice sheet variability since the early Pleistocene.
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Barker S, Starr A, van der Lubbe J, Doughty A, Knorr G, Conn S, Lordsmith S, Owen L, Nederbragt A, Hemming S, Hall I, Levay L, Berke MA, Brentegani L, Caley T, Cartagena-Sierra A, Charles CD, Coenen JJ, Crespin JG, Franzese AM, Gruetzner J, Han X, Hines SKV, Jimenez Espejo FJ, Just J, Koutsodendris A, Kubota K, Lathika N, Norris RD, Periera Dos Santos T, Robinson R, Rolison JM, Simon MH, Tangunan D, Yamane M, and Zhang H
- Abstract
Prior to ~1 million years ago (Ma), variations in global ice volume were dominated by changes in obliquity; however, the role of precession remains unresolved. Using a record of North Atlantic ice rafting spanning the past 1.7 million years, we find that the onset of ice rafting within a given glacial cycle (reflecting ice sheet expansion) consistently occurred during times of decreasing obliquity whereas mass ice wasting (ablation) events were consistently tied to minima in precession. Furthermore, our results suggest that the ubiquitous association between precession-driven mass wasting events and glacial termination is a distinct feature of the mid to late Pleistocene. Before then (increasing), obliquity alone was sufficient to end a glacial cycle, before losing its dominant grip on deglaciation with the southward extension of Northern Hemisphere ice sheets since ~1 Ma.
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- 2022
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48. Tirons of the world: a review of tironid amphipods, description of new genera and species, and establishment of a new subfamily Tironinae Stebbing, 1906 stat. nov. (Crustacea, Synopiidae).
- Author
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Just J
- Subjects
- 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt, Animals, Australia, Amphipoda
- Abstract
The classification of a group of Synopiidae is reviewed based primarily on new material from Australasia and the northern Pacific. A synopiid subfamily, Tironinae Stebbing, 1906 stat. nov. is diagnosed for the following six genera (3 new) consisting of 38 species (18 new): Tiron Lilljeborg, 1865, with 6 species, T. spiniferus Stimpson (type species), T. antarcticus K.H. Barnard, 1932, T. biocellatus J.L. Barnard, 1962, T. canadense sp. nov., T. lilljeborgi sp. nov., and T. sagamiense sp. nov.; Tironella gen. nov. with 3 species, T. altifrons (Reid, 1951, ex Tiron) comb. nov., T. bathyalis sp. nov. (type species), and T. pervicax (J.L. Barnard, 1967, ex Pseudotiron) comb. nov.; Glandulotiron gen. nov. with 15 species, G. pilocaputis sp. nov. (type species), G. salsevisio sp. nov., G. hexamatius sp. nov., G. spinipes sp. nov., G. concavus sp. nov., G. septimus sp. nov., G. meruspinosus sp. nov., G. bassianus sp. nov., G. curvispinus sp. nov., G. aotearoensis sp. nov., G. postremus sp. nov., G. griffithsi sp. nov., G. intermedius (Reid, 1951; ex Tiron) comb. nov., G. quadrioculatus (Dang Le, 2012; ex Tiron) comb. nov., and G. australis (Stebbing, 1908; ex Tiron) comb. nov.; Pseudotiron Chevreux, 1895 with 4 species, P. bouvieri Chevreux, 1895, P. coas J.L. Barnard, 1967, P. golens J.L. Barnard, 1962, P. miratus sp. nov.; Metatiron Rabindranath, 1972, with 4 species, M. brevidactylus (Pillai, 1954, type species), M. bonaerensis Alonso de Pina, 1998, M. triocellatus (Goeke, 1982) and M. tropakis (J.L. Barnard, 1972); and Minitiron gen. nov. with 6 species, M. orpheus sp. nov. (type species), M. bellairsi (Just, 1981; ex. Metatiron) comb. nov., M. caecus (Ledoyer, 1979; ex. Metatiron) comb. nov., M. galeatus (Hirayama, 1988; ex Tiron) comb. nov., M. ovatibasis (Hirayama, 1988; ex Tiron) comb. nov., M. thompsoni (Walker, 1904; ex Tiron) comb. nov. Three species currently in Pseudotiron (P. longicaudatus Pirlot, 1934; P. sublongicaudatus Dang Le, 2012; P. livingstonae Lrz Coleman, 2013) are removed to Synopiidae incertae sedis. Metatiron brevidactylus (Pillay, 1957) by Ledoyer (1979) is removed to Minitiron incerta sedis. Species in the new genus Glandulotiron and a new species of Pseudotiron possess rows of elongate glands in uropods and the telson previously unknown in amphipods. A new key is presented for synopiid genera together with a key to world tironin genera and separate keys for the individual tironin genera. Global distribution and more detailed Australian distribution of the tironins are shown.
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- 2022
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49. Specialized Outpatient Palliative Care—Clinical Course and Predictors for Living at Home Until Death
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Just J, Schmitz MT, Grabenhorst U, Joist T, Horn K, and Weckbecker K
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- Ambulatory Care, Female, Germany epidemiology, Humans, Outpatients, Retrospective Studies, Palliative Care, Terminal Care
- Abstract
Background: Specialized outpatient palliative care (SOPC) is an important component of the palliative medicine care concept in Germany. Its purpose is to improve the out-of-hospital care of patients who cannot be adequately cared for by their primary care physicians and in the setting of general outpatient palliative care (GOPC)., Methods: In this retrospective analysis of anonymized routine treatment data, we analyzed the characteristics of SOPC patients overall and with specific diseases, and depicted them both numerically and graphically. We also carried out a regression analysis of the factors affecting whether or not patients will be able to die in a home environment., Results: The analysis included data from 14 460 patients who were treated by 14 different SOPC teams in the North Rhine area of Germany in 2017 and 2018. The majority of patients who died were able to live at home until death (85.9%); only a small percentage died as inpatients (7.7%). The symptom burden shortly before death was less than at the beginning of treatment. The factors displaying a statistically significant association with dying at home were: more advanced age (aOR 0.96; 95% CI: [0.95; 0.96]), female sex (aOR 0.85; 95% CI: [0.74; 0.98]), and house calls at night (aOR 0.60; 95% CI: [0.51; 0.71])., Conclusion: SOPC met its declared objectives of limiting distressing symptoms and enabling patients to live at home until death.
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- 2022
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50. Custom methods to identify conserved genetic modules applied to novel transcriptomic data from Amborella trichopoda.
- Author
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Rivarola Sena AC, Andres-Robin A, Vialette AC, Just J, Launay-Avon A, Borrega N, Dubreucq B, and Scutt CP
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- Flowers genetics, Phylogeny, Seeds, Transcriptome, Arabidopsis genetics, Arabidopsis metabolism, Magnoliopsida metabolism
- Abstract
We have devised a procedure for the inter-species comparison of transcriptomic data and used this procedure to reconstruct the expression dynamics of major genetic modules that were present at least 149 million years ago in the most recent common ancestor of living angiosperms. We began by using laser-assisted microdissection to generate novel transcriptomic data from female flower tissues of Amborella trichopoda, the likely sister to all other living angiosperms. We then employed a gene-expression clustering method, followed by a custom procedure to compare genetic modules on the basis of gene orthology between Amborella and the molecular-genetic model angiosperm Arabidopsis thaliana. Using this protocol, we succeeded in identifying nine major genetic modules that appear to have conserved their expression dynamics from an early stage in angiosperm evolution. The genes of these modules, representing over 5000 orthogroups, include around one third of those known to control female reproductive development in Arabidopsis. Our study constitutes a proof of concept for the comparison of transcriptomic data between widely diverged plant species and represents a first step in the large-scale analysis of gene expression dynamics in a macro-evolutionary context., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
- Full Text
- View/download PDF
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