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Journal of Palaeogeography 2015年第3期4卷 248-250页

作者： christian vérard Institute for Environmental Science University of Geneva

I use to say that in science, one cannot say what is right, but one can say what is wrong. And a model is, by definition, wrong, otherwise it is not a modet, it is the truth. Being aware that a model aims to mimic the truth but witl never be the truth, the onty worth questions asking to a model are：（1） How wrong are we？ And （2） Why are we wrong？ The tatter questions the foundations of the model, and is mainty the concerns of A. J. （Tom） van Loon＇s comments （2015, this issue）. The first questions the accuracy of the outcomes, and corresponds more to G. Shanmugam＇s comments （2015, this issue）. I am grad that our paper has aroused so rapidty as much feedbacks and comments, sometimes even before the manuscript is definitely pubtished. We hope this paper witl keep on inspiring various axes of research and opening new avenues in geosciences. Detaited answers to the comments raised by A. J. （Tom） van Loon and G. Shanmugam among others would certainty deserve a book, so my repty witl just focus herein around the two aforementioned questions.

关键词： modet topography pataeogeographicreconstruction plate tectonics geoscience

Modeling the Middle Jurassic ocean circulation

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Journal of Palaeogeography 2015年第4期4卷 373-386页

作者： Maura Brunetti christian vérard Peter O.Baumgartner Institute for Environmental Sciences University of Geneva Institute of Earth Sciences University of Lausanne

We present coupled ocean-sea-ice simulations of the Middle Jurassic（~165 Ma） when Laurasia and Gondwana began drifting apart and gave rise to the formation of the Atlantic Ocean. Since the opening of the Proto-Caribbean is not well constrained by geological records, configurations with and without an open connection between the Proto-Caribbean and Panthalassa are examined. We use a sea-floor bathymetry obtained by a recently developed three-dimensional（3D） elevation model which compiles geological, palaeogeographical and geophysical data. Our original approach consists in coupling this elevation model, which is based on detailed reconstructions of oceanic realms, with a dynamical ocean circulation model. We find that the Middle Jurassic bathymetry of the Central Atlantic and Proto-Caribbean seaway only allows for a weak current of the order of 2 Sv in the upper 1000 m even if the system is open to the West. The effect of closing the western boundary of the Proto-Caribbean is to increase transport related to barotropic gyres in the southern hemisphere and to change water properties, such as salinity, in the Neo-Tethys. Weak upwelling rates are found in the nascent Atlantic Ocean in the presence of this superficial current and we discuss their compatibility with deep-sea sedimentological records in this region.

关键词： Jurassic modeling ocean circulation palaeoclimate

3D palaeogeographic reconstructions of the Phanerozoic versus sea-level and Sr-ratio variations

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Journal of Palaeogeography 2015年第1期4卷 64-84页

作者： christian vérard Cyril Hochard Peter O.Baumgartner Gérard M.Stampfli Université de Lausanne (UNIL) Institut des Sciences de la Terre (ISTE)Geopolis Ch–1015 Lausanne Switzerland

A full global geodynamical model over 600 million years （Ma） has been de- veloped at the University of Lausanne during the past 20 years. We show herein how the 2D maps were converted into 3D （i.e., full hypsometry and bathymetry）, using a heuristic-based approach. Although the synthetic topography may be viewed as relatively crude, it has the advantage of being applicable anywhere on the globe and at any geological time. The model allows estimating the sea-level changes throughout the Phanerozoic, with the possibility, for the first time, to flood accordingly continental areas. One of the most striking results is the good correlation with ＂measured＂ sea-level changes, implying that long-term variations are predominantly tectonically-driven. volumes of mountain relief are also estimated through time and compared with strontium isotopic ratio （Sr-ratio）, commonly thought to reflect mountain belt erosion. The tectonic impact upon the general Sr-retio trend is shown herein for the first time, although such influence was long been inferred.

关键词： palaeogeography reconstruction hypsometry bathymetry sea-level Sr-ratio tectonic-climate relationship

Geodynamic evolution of the Earth over the Phanerozoic:Plate tectonic activity and palaeoclimatic indicators

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Journal of Palaeogeography 2015年第2期4卷 167-188页

作者： christian vérard Cyril Hochard Peter O.Baumgartner Gérard M.Stampfli Université de Lausanne (UNIL) Institut des Sciences de la Terre (ISTE)

During the last decades, numerous local reconstructions based on field geol- ogy were developed at the University of Lausanne （UNIL）. Team members of the UNIL partici- pated in the elaboration of a 600 Ma to present global plate tectonic model deeply rooted in geological data, controlled by geometric and kinematic constraints and coherent with forces acting at plate boundaries. In this paper, we compare values derived from the tectonic model （ages of oceanic floor, production and subduction rates, tectonic activity） with a combination of chemical proxies （namely CO2, 87Sr/86Sr, glaciation evidence, and sea-level variations） known to be strongly in- fluenced by tectonics. One of the outstanding results is the observation of an overall decreas- ing trend in the evolution of the global tectonic activity, mean oceanic ages and plate velocities over the whole Phanerozoic. We speculate that the decreasing trend reflects the global cooling of the Earth system. Additionally, the parallel between the tectonic activity and CO2 together with the extension of glaciations confirms the generally accepted idea of a primary control of CO2 on climate and highlights the link between plate tectonics and CO2 in a time scale greater than 107 yr. Last, the wide variations observed in the reconstructed sea-floor production rates are in contradiction with the steady-state model hypothesized by some.

关键词： geodynamic plate tectonics plate model Phanerozoic palaeoclimate CO2,strontium glaciation

Cellular models of stress resistance may pave ways to fight neurodegenerative diseases

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Neural Regeneration Research 2025年第9期20卷 2579-2580页

作者： Thu Nguyen Minh Pham christian Behl Institute of Pathobiochemistry University Medical Center of the Johannes Gutenberg UniversityMainzGermany

Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron *** entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to ***,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.

关键词： cortex resistance Alzheimer

Many faces of neuronal activity manipulation in Drosophila

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Neural Regeneration Research 2025年第9期20卷 2574-2576页

作者： Amber Krebs Steffen Kautzmann christian Klämbt Institut für Neuro-und verhaltensbiologie MünsterGermany

Animals exhibit complex responses to external and internal *** information is computed by interconnected neurons that express numerous ion channels,which modulate the neuronal membrane *** can neuronal activity orchestrate complex motor patterns or allow learning from previous experience?To answer such questions,we need the ability not only to record,but also to modulate neuronal activity in both space(e.g.,neuronal subsets)and time.

关键词： manipulation potential. neuronal

Anticancer Properties and Mechanism of Action of Oblongifolin C,Guttiferone K and Related Polyprenylated Acylphloroglucinols

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Natural Products and Bioprospecting 2021年第6期11卷 629-641页

作者： christian Bailly Gérard vergoten Scientific Consulting Office OncoWitan59290 LilleWasquehalFrance Inserm INFINITE-U1286Facultéde PharmacieUniversity of LilleInstitut de Chimie Pharmaceutique Albert Lespagnol(ICPAL)3 rue du Professeur LaguesseBP-8359006 LilleFrance

Polyprenylated acylphloroglucinols represent an important class of natural products found in many *** them,the two related products oblongifolin C(Ob-C)and guttiferone K(Gt-K)isolated from Garcinia species(notably from edible fruits),have attracted attention due to their marked anticancer *** two compounds only differ by the nature of the C-6 side chain,prenyl(Gt-K)or geranyl(Ob-C)on the phloroglucinol *** origin,method of extraction and biological properties are presented here,with a focus on the targets and pathways implicated in their anticancer *** compounds markedly reduce cancer cell proliferation in vitro,as well as tumor growth and metastasis in *** are both potent inducer of tumor cell apoptosis,and regulation of autophagy flux is a hallmark of their mode of *** distinct mechanism leading to autophagosome accumulation in cells and the implicated molecular targets are *** specific role of the chaperone protein HSPA8,known to interact with Ob-C,is *** models of Gt-K and Ob-C bound to HSPA8 provide a structural basis to their common HSPA8-binding recognition *** review shed light on the mechanism of action of these compounds,to encourage their studies and potential development.

关键词： Anticancer Autophagy HSPA8 Natural products Polyprenylated acylphloroglucinols

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts christian Mustroph David Gimbel Jonathan Grossberg Daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

Molecular modeling of alkaloids bouchardatine and orirenierine binding to sirtuin-1(SIRT1)

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Digital Chinese Medicine 2022年第3期5卷 276-285页

作者： Gérard vergoten christian Bailly Inserm INFINITE-U1286Institut de Chimie Pharmaceutique Albert Lespagnol(ICPAL)Faculty of PharmacyUniversity of LilleLille 59006France Scientific Consulting Office OncoWitanLille 59290France

Objective Bouchardatine(1)is a β-indoloquinazoline alkaloid isolated from the plant Bouchardatia neurococca,acting as a modulator of adipogenesis and lipogenesis,and as an anticancer *** natural product functions as an activator of proteins adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)and sirtuin 1(SIRT1).We used molecular modeling to investigate the SIRT1-binding capacity of compound 1 and various structural analogues,such as orirenierine A(2)and orirenierine B(3)isolated from the medicinal plant Oricia *** We investigated the binding to human SIRT1(hSIRT1)of 25 natural products including theβ-indoloquinazoline alkaloids 1−3 and analogues,in comparison with the reference product sirtinol(R and S isomers).A sirtinol binding model was elaborated starting from the closed and open state conformations of the catalytic domain of hSIRT1(PDB structures 4KXQ and 4IG9).For each compound bound to SIRT1,the empirical energy of interaction(ΔE)was calculated and compared to that of *** In our model,compound 1 was found to bind modestly to the sirtinol site of *** contrast,the presence of a phenolic OH group at position 7 on the quinazolinone moiety conferred a much higher binding *** 2 provided SIRT1 protein complexes as stable as those observed with *** replacement of the hydroxy substituent(2)with a methoxy group(3)reduced the SIRT1 binding *** SIRT1-binding natural products were identified,such as the alkaloids orisuaveolines A and ***-binding relationships were *** The study underlines the capacity of β-indoloquinazoline alkaloids to interact with *** deacetylase enzyme could represent a molecular target for the alkaloid *** compound merits further attention for the design of drugs active against SIRT1-dependent pathologies.

关键词： Sirtuin 1(SIRT1) Alkaloids Bouchardatine Orirenierine Natural products Cancer Inflammatory diseases Molecular modeling Drug design

Molecular docking study of xylogranatins binding to glycogen synthase kinase-3β

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Digital Chinese Medicine 2022年第1期5卷 9-17页

作者： christian Baillya Gérard vergoten Scientific Consulting Office OncoWitanWasquehalLille 59290France University of Lille InsermINFINITE-U1286Institut de Chimie Pharmaceutique Albert Lespagnol(ICPAL)Faculty of Pharmacy3 rue du Professeur LaguesseBP-83F-59006LilleFrance

Objective The mangrove tree Xylocarpus granatum ***(***)is a medicinal plant used to treat various diseases in several Asian *** bioactive natural products have been isolated from the plants,particularly several groups of limonoids,including 18 xylogranatins(Xyl-A to R),all of which bear a furyl-δ-lactone core commonly found in *** on a structural analogy with the limonoids obacunone and gedunin,we hypothesized that xylogranatins could target the enzyme glycogen synthase kinase-3β(GSK-3β),a major target for the treatment of neurodegenerative pathologies,viral infections,and *** We investigated the binding of the 18 xylogranatins to GSK-3βusing molecular docking in comparison with two known reference GSK-3βATP-competitive inhibitors,LY2090314 and *** each compound bound to GSK-3β,the empirical energy of interaction(ΔE)was calculated and compared to that obtained with known GSK-3βinhibitors and limonoid triterpenes that target this *** Five compounds were identified as potential GSK-3βbinders,Xyl-A,-C,-J,-N,and-O,for which the calculated empiricalΔE was equivalent to that calculated using the best reference molecule *** best ligand is Xyl-C,which is known to have marked anticancer *** of Xyl-C to the ATP-binding pocket of GSK-3βpositions the furyl-δ-lactone unit deep into the binding-site *** xylogranatin derivatives bearing a central pyridine ring or a compact polycyclic structure are much less adapted for GSK-3β***-binding relationships are *** GSK-3βmay contribute to the anticancer effects of *** *** study paves the way for the identification of other furyl-δ-lactone-containing limonoids as GSK-3βmodulators.

关键词： Natural products Xylocarpus granatum Xylogranatins Glycogen synthase kinase-3β(GSK-3β) Limonoids Cancer Molecular modelling Structure-activity relationship