Article
Genetics & Heredity
Przemyslaw Kosinski, Malgorzata Kedzia, Adrianna Mostowska, Pawel Gutaj, Michal Lipa, Ewa Wender-Ozegowska, Adriana Rozy, Joanna Chorostowska-Wynimko, Miroslaw Wielgos, Aleksandra Jezela-Stanek
Summary: The study revealed an increased prevalence of the SERPINA1 PI*Z variant in women with intrahepatic cholestasis, suggesting a possible genetic origin of a higher risk of intrahepatic cholestasis in pregnancy.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Peijie Wu, Ling Qiao, Han Yu, Hui Ming, Chao Liu, Wenjun Wu, Baixue Li
Summary: The study demonstrates that arbutin has a protective effect on cholestatic liver injury induced by ANIT by upregulating FXR and downstream enzymes associated with bile acid homeostasis. Furthermore, the findings suggest that arbutin may be a potential chemical molecule for cholestatic diseases by partly acting through the FXR pathway.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jan C. Kamp, Naomi N. Kappe, Carlos Fernandez Moro, Jan Fuge, Mark P. Kuehnel, Sabine Wrenger, Tobias Welte, Bart van Hoek, Danny D. Jonigk, Padmini P. S. J. Khedoe, Pavel Strnad, Mikael Bjornstedt, Jan Stolk, Sabina Janciauskiene, Antal Nemeth
Summary: PiZZ (Glu342Lys) alpha 1-antitrypsin deficiency (AATD) is a risk factor for liver disease development in children, characterized by intrahepatic AAT polymerization. The presence of Z-AAT polymers in hepatocytes is common among PiZZ children, but the clinical outcomes vary, with some developing neonatal cholestasis and cirrhosis. The expression of genes related to liver fibrosis/cirrhosis and lipid, aldehyde/ketone, and bile acid metabolism differ between groups, suggesting that changes in specific genes and pathways may reflect the degree of liver injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Pavel Strnad, Mattias Mandorfer, Gourab Choudhury, William Griffiths, Christian Trautwein, Rohit Loomba, Thomas Schluep, Ting Chang, Min Yi, Bruce D. Given, James C. Hamilton, Javier San Martin, Jeffery H. Teckman
Summary: The trial demonstrated that fazirsiran treatment in patients with liver disease associated with AAT deficiency led to a significant reduction in Z-AAT concentrations in the liver and serum, as well as improvements in liver enzyme concentrations, showing potential therapeutic effects on liver fibrosis.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Respiratory System
Alexa Nunez, Irene Belmonte, Elena Miranda, Miriam Barrecheguren, Georgina Farago, Eduardo Loeb, Monica Pons, Francisco Rodriguez-Frias, Pablo Gabriel-Medina, Esther Rodriguez, Joan Genesca, Marc Miravitlles, Cristina Esquinas
Summary: This study investigated the association between levels of CP of AAT with severity of lung and liver disease in AATD patients. Pi*ZZ patients had the highest CP concentrations, especially those with impaired lung function and increased liver stiffness. These findings suggest that CP may be helpful in identifying patients at higher risk of developing lung and liver disease.
RESPIRATORY RESEARCH
(2021)
Article
Obstetrics & Gynecology
J. Fleminger, P. T. Seed, A. Smith, E. Juszczak, P. H. Dixon, J. Chambers, J. Dorling, C. Williamson, J. G. Thornton, L. C. Chappell
Summary: The study found that there was no specific group of women with intrahepatic cholestasis of pregnancy who would benefit from treatment with ursodeoxycholic acid, indicating that its routine use for improvement of bile acid concentration or itch score should be reconsidered.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nazli Khodayari, Rejean L. Wang, Regina Oshins, Yuanqing Lu, Michael Millett, Alek M. Aranyos, Sayedamin Mostofizadeh, Yogesh Scindia, Tammy O. Flagg, Mark Brantly
Summary: Alpha-1 antitrypsin deficiency (AATD) is caused by a single mutation in the SERPINA1 gene, leading to the accumulation of misfolded alpha-1 antitrypsin (ZAAT) in hepatocytes, which is associated with mitochondrial dysfunction. Research has shown that ZAAT aggregation in hepatocytes results in abnormal mitochondrial morphology and function, disrupting lipid metabolism balance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Monica Pons, Alexa Nunez, Cristina Esquinas, Maria Torres-Duran, Juan Luis Rodriguez-Hermosa, Myriam Calle, Ramon Tubio-Perez, Irene Belmonte, Francisco Rodriguez-Frias, Esther Rodriguez, Joan Genesca, Marc Miravitlles, Miriam Barrecheguren
Summary: Transient elastography can help identify AATD patients with liver fibrosis, even if liver enzymes are normal. Patients with AATD frequently have abnormal liver enzymes, but most of them do not have significant liver fibrosis.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Nan He, Xiaoming Liu, Amber R. Vegter, T. Idil A. Evans, Jaimie S. Gray, Junfeng Guo, Shashanna R. Moll, Lydia J. Guo, Meihui Luo, Ningxia Ma, Xingshen Sun, Bo Liang, Ziying Yan, Zehua Feng, Lisi Qi, Arnav S. Joshi, Weam Shahin, Yaling Yi, Katherine N. Gibson-Corley, Eric A. Hoffman, Kai Wang, Christian Mueller, John F. Engelhardt, Bradley H. Rosen
Summary: Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause and risk factor for chronic obstructive pulmonary disease. This study used ferret models to demonstrate that complete loss of AAT and the most common mutation in AAT result in lung and hepatic diseases similar to those observed in AATD patients, making them a potential platform for preclinical testing of therapeutics including gene therapy.
Review
Pharmacology & Pharmacy
Dhiren Patel, Jeffrey Teckman
Summary: Alpha-1 antitrypsin deficiency (AATD) liver disease is the second leading cause of death among patients with the condition, primarily due to diverse manifestations of liver disease caused by AAT aggregates within hepatocytes. Although there is currently no licensed treatment for AATD-related liver disease, liver transplantation may yield positive outcomes.
THERAPEUTIC ADVANCES IN CHRONIC DISEASE
(2021)
Article
Pediatrics
Christina Louise Winther, Sofie Nyrann, Rasmus Gaardskaer Nielsen, Morten Duno, Klaus Birkelund Johansen, Thora Wesenberg Helt, Vibeke Brix Christensen
Summary: This study assessed the changes in growth, lung function, and liver function in Danish children with alpha-1 antitrypsin deficiency. The results showed that these children had low weight-for-height Z-scores at diagnosis but experienced catch-up growth during the first year of life. Children with ZZ-homozygosity had higher serum concentrations of liver enzymes throughout childhood compared to children with heterozygosity.
Article
Gastroenterology & Hepatology
Sameer Prakash, Arvind R. Murali
Summary: This study investigated whether alpha-1 antitrypsin (A1AT) genotype testing should be the primary screening method for A1AT heterozygous variants. Median and interquartile range of A1AT levels were calculated for different genotypes in 4378 patients with chronic liver disease, and the miss rates of MZ genotype identification at various cutoff levels were determined. There was significant overlap in A1AT levels among Pi*MM, MZ, and MS variants. The miss rates of Pi*MZ were 29%, 18%, 8%, and 4% at cutoff levels <100, <110, <120, and <130, respectively. Therefore, simultaneous measurement of A1AT levels and genotypes is recommended in patients with chronic liver disease.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Daniella A. Spittle, Alison Mansfield, Anita Pye, Alice M. Turner, Michael Newnham
Summary: The progression of lung disease in alpha-1 antitrypsin deficiency (AATD) varies and presents differently. Blood biomarkers are a convenient and repeatable method of monitoring diseases. In this study, we compared the levels of seven serum biomarkers between AATD patients with and without COPD. We found that CRP and CCL18 were significantly higher in AATD COPD patients. CC16 was found to be predictive of emphysema progression in AATD COPD.
Article
Gastroenterology & Hepatology
Christoph Grander, Benedikt Schaefer, Julian Schwaerzler, Felix Grabherr, Dennis M. de Graaf, Barbara Enrich, Georg Oberhuber, Lisa Mayr, Moris Sangineto, Nikolai Jaschke, Timon E. Adolph, Maria Effenberger, Alexander R. Moschen, Charles A. Dinarello, Heinz Zoller, Herbert Tilg
Summary: ALD is a global healthcare issue with limited treatment options. AAT has shown potent anti-inflammatory activities and low serum concentrations are associated with increased risk of death/liver transplantation in cirrhotic ALD patients. Experimental models in mice suggest that AAT may be a potential therapeutic option for ALD, especially for alcoholic hepatitis.
Article
Gastroenterology & Hepatology
Neng-Li Wang, Jing Lin, Lian Chen, Yi Lu, Xin-Bao Xie, Kuerbanjiang Abuduxikuer, Jian-She Wang
Summary: This study found that liver manifestations of ASMD in early stages include hepatosplenomegaly, elevated transaminases, and liver foam cells, which may present as neonatal cholestasis. It is important to be cautious when using low HDL-C for aiding diagnosis, as cholestasis can be a pitfall in infants with splenomegaly.
BMC GASTROENTEROLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Panayotis Lykavieris, Olivier Bernard, Emmanuel Jacquemin
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2021)
Article
Optics
Olivier Bernard, Yves Bellouard
Summary: The use of femtosecond lasers provides a versatile method for encoding information and modifying transparent materials with sub-micron resolution, thanks to the non-linear nature of laser-matter interaction. However, achieving repeatable and accurate results relies heavily on time-consuming machine-specific calibration and experiment-specific fine-tuning due to the complex physical processes involved.
JOURNAL OF PHYSICS-PHOTONICS
(2021)
Article
Automation & Control Systems
Walid Djema, Laetitia Giraldi, Sofya Maslovskaya, Olivier Bernard
Summary: The paper focuses on a generic optimal control problem derived from competition between two microbial populations, characterizing the optimal control strategy using Pontryagin's Maximum Principle and providing conditions for the existence of a turnpike property. Illustrative results are shown on microalgae using numerical methods.
Article
Mathematics, Applied
Agustin G. Yabo, Jean-Baptiste Caillau, Jean-Luc Gouze, Hidde de Jong, Francis Mairet
Summary: Gaining a better understanding of microbial growth is crucial for scientific research, and self-replicator models based on resource allocation principles have been effective in explaining experimental observations. This study extends a previous model by considering the role of proteins in basic functions and investigates their impact on optimal resource allocation strategies in response to environmental changes. The analysis reveals a globally attractive equilibrium and complex solutions, providing a generalized perspective on microbial growth analysis.
SIAM JOURNAL ON APPLIED DYNAMICAL SYSTEMS
(2022)
Article
Plant Sciences
Anne Pajot, Johann Lavaud, Gregory Carrier, Matthieu Garnier, Bruno Saint-Jean, Noemie Rabilloud, Caroline Baroukh, Jean-Baptiste Berard, Olivier Bernard, Luc Marchal, Elodie Nicolau
Summary: Differences in lhc classification in Chromista were observed. A classification of the lhcf family with specific groups for haptophytes, diatoms, and seaweeds was proposed. Similarity analysis was performed to identify and characterize Fucoxanthin and Chlorophyll a/c-binding Protein (FCP) in the haptophyte microalgae Tisochrysis lutea. The study revealed dynamic changes in lhc gene expression with nitrogen depletion and the exclusive nighttime expression of the lhcx2 gene in T. lutea, suggesting its role in protecting cells from light exposure after prolonged darkness.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Automation & Control Systems
Olivier Bernard, Liu-Di Lu, Julien Salomon
Summary: In this article, the authors investigate a periodic resource allocation problem in a dynamical system, which is applied to a biological system. The goal is to find optimal control strategies to optimize the cost or benefit of the system. The authors illustrate this problem using an industrial biological application and introduce a nonlinear optimization problem and a suboptimal solution to overcome the computational difficulty. Numerical experiments are performed to assess the benefits of optimal strategies in different settings.
INTERNATIONAL JOURNAL OF ROBUST AND NONLINEAR CONTROL
(2023)
Article
Biochemical Research Methods
Bastien Polizzi, Andrea Fanesi, Filipa Lopes, Magali Ribot, Olivier Bernard
Summary: This article presents a spatial model for the growth of a photosynthetic microalgae biofilm and investigates the biofilm's structural dynamics and the impact of optimal harvesting strategies on its structure.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Engineering, Chemical
Walid Djema, Terence Bayen, Olivier Bernard
Summary: This paper investigates the problem of species separation in minimal time. The evolution of two competing microorganism populations for the same resource is described using the Droop model. The paper focuses on solving an optimal control problem subject to a controlled system with five dimensions. The objective is to select the desired species in minimal time and synthesize an optimal feedback control. The paper provides properties of optimal controls and utilizes the Pontryagin Maximum Principle and a study of singular arcs for analysis. The theoretical results are validated using numerical examples with microalgae and a direct method in optimal control.
Article
Biotechnology & Applied Microbiology
Andrea Fanesi, Thierry Martin, Cyril Breton, Olivier Bernard, Romain Briandet, Filipa Lopes
Summary: Microalgae biofilms have ecological importance and biotechnological potential. However, a comprehensive understanding of their structure and physiology is still lacking. In this study, a novel approach was developed to nondestructively characterize the physiological and structural information of microalgae biofilms. The results showed that the physiology of cells in complex biofilms is more affected, likely due to alterations in local environmental conditions.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Microbiology
Francesca Casagli, Olivier Bernard
Summary: High-rate algal-bacterial ponds (HRABP) are considered as an interesting solution to reduce energy demand in wastewater treatment, yet the efficiency is highly influenced by solar fluxes and temperature fluctuations. The temperature patterns and reactor configurations play a crucial role in the biological process of HRABPs.
Article
Automation & Control Systems
Frederic Mazenc, Olivier Bernard
Summary: This article presents a simple, necessary, and sufficient condition for a real matrix to be similar to a Metzler matrix of dimension three, and provides a construction method for the transfer matrix. This construction is utilized to design an interval observer for a family of continuous-time systems. The case of limit cycles in the love dynamics is used as an example for the interval observer design.
IEEE TRANSACTIONS ON AUTOMATIC CONTROL
(2022)
Article
Green & Sustainable Science & Technology
Francesca Casagli, Olivier Bernard
Summary: Existing mathematical models for outdoor biotechnological processes cannot predict the future dynamics, thus fully predictive models are needed. The FLAME modelling framework integrates biological, heat transfer, and chemical sub-models to forecast outdoor bioprocesses. It provides a powerful tool for controlling and optimizing environmental processes.
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Biotechnology & Applied Microbiology
David Morgado, Andrea Fanesi, Thierry Martin, Sihem Tebbani, Olivier Bernard, Filipa Lopes
Summary: This study utilized a rotating system to produce the high-value compound astaxanthin using Haematococcus pluvialis biofilms. The effect of nitrogen regime, light intensity, and light history on biofilm traits was assessed, showing that H. pluvialis biofilms follow the classical growth stages of bacterial biofilms and that training the biofilms during the green stage can significantly enhance astaxanthin productivity.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Proceedings Paper
Automation & Control Systems
Carlos Martinez, Bruno Assis Pessi, Olivier Bernard
Summary: This paper examines the dynamics and productivity of biomass in a continuous microalgae culture contaminated by predators. The study presents a model outlining the system where photolimited microalgae are grazed by zooplankton, discussing conditions for coexistence equilibrium and the behavior of microalgae and predators in different scenarios. Numerical simulations demonstrate that operating the system at an optimal dilution rate can lead to the extinction of predators.
Letter
Gastroenterology & Hepatology
Giuseppe Maggiore, Andrea Pietrobattista, Daniela Liccardo, Marco Sciveres, Silvia Nastasio, Emmanuel Jacquemin, Olivier Bernard
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
(2021)