Knowing the phase relations of carbon-bearing phases at high-pressure(HP) and high-temperature(HT) condition is essential for understanding the deep carbon cycle in the subduction zones.In particular,the phase relatio...Knowing the phase relations of carbon-bearing phases at high-pressure(HP) and high-temperature(HT) condition is essential for understanding the deep carbon cycle in the subduction zones.In particular,the phase relation of carbon-bearing phases is also strongly influenced by redox condition of subduction zones,which is poorly explored.Here we summarized the phase relations of carbon-bearing phases(calcite,aragonite,dolomite,magnesite,graphite,hydrocarbon) in HP metamorphic rocks(marble,metapelite,eclogite) from the Western Tianshan subduction zone and high-pressure experiments.During prograde progress of subduction,carbonates in altered oceanic crust change from Ca-carbonate(calcite) to Ca,Mg-carbonate(dolomite),then finally to Mgcarbonate(magnesite) via Mg-Ca cation exchange reaction between silicate and carbonate,while calcite in sedimentary calcareous ooze on oceanic crust directly transfers to high-pressure aragonite in marble or amorphous CaCO3 in subduction zones.Redox evolution also plays a significant effect on the carbon speciation in the Western Tianshan subduction zone.The prograde oxygen fugacity of the Western Tianshan subduction zone was constrained by mineral assemblage of garnet-omphacite from FMQ-1.9 to FMQ-2.5 at its metamorphic peak(maximum P-T) conditions.In comparison with redox conditions of other subduction zones,Western Tianshan has the lowest oxygen fugacity.Graphite and light hydrocarbon inclusions were ubiqutously identified in Western Tianshan HP metamorphic rocks and speculated to be formed from reduction of Fe-carbonate at low redox condition,which is also confirmed by high-pressure experimental simulation.Based on petrological observation and high-pressure simulation,a polarized redox model of reducing slab but oxidizing mantle wedge in subduction zone is proposed,and its effect on deep carbon cycle in subduction zones is further discussed.展开更多
Semen from 10 932 male partners of infertile couples was analysed and sperm parameter trends were evaluated at the Reproduction Biology Laboratory of the University Hospital of Marseille （France） between 1988 and 20...Semen from 10 932 male partners of infertile couples was analysed and sperm parameter trends were evaluated at the Reproduction Biology Laboratory of the University Hospital of Marseille （France） between 1988 and 2007. After 3-6 days of abstinence, semen samples were collected. Measurements of seminal fluid volume, pH, sperm concentration, total sperm count, motility and detailed morphology of spermatozoa were performed. Sperm parameters were analysed on the entire population and in men with normal total numeration （ 〉~ 40 million per ejaculate）. The whole population demonstrated declining trends in sperm concentration （1.5% per year）, total sperm count （1.6% per year）, total motility （0.4% per year）, rapid motility （5.5% per year） and normal morphology （2.2% per year）. In the group of selected samples with total normal sperm count, the same trends of sperm quality deterioration with time were observed. Our results clearly indicate that the auality of semen decreased in this population over the study period.展开更多
Mechanical properties,such as the hardness H,Young’s modulus E,creep modulus C,and fracture toughness Kc,are essential parameters in the design of hydraulic fracturing systems for prospective shale gas formations.In ...Mechanical properties,such as the hardness H,Young’s modulus E,creep modulus C,and fracture toughness Kc,are essential parameters in the design of hydraulic fracturing systems for prospective shale gas formations.In this study,a practical methodology is presented for obtaining these properties through microindentation experiments combined with quantitative observations of the mineralogical phases using X-ray diffraction(XRD),scanning electron microscopy(SEM)with backscattered electron(BSE)imaging,and energy-dispersive X-ray spectroscopy(EDS)analyses.We apply this method in the case of three types of Longmaxi shales with different mineralogies(i.e.carbonate-,clay-,and quartz-rich,respectively),which allows us to determine the characteristic indentation depth,hc?8e10 mm,beyond which the mechanical response of the carbonate-rich shale is homogeneous and independent of its complex heterogeneous microstructure.Moreover,exploiting the results of a large number of indentation tests,we demonstrate that the indentation modulus M of the shale increases as a power-law of hardness H,and its creep modulus C increases linearly with H.We also compute the fracture toughness Kc from the indentation data by assuming a perfectly plastic behavior of the sample.Our results are in good agreement with independent measurements of Kc determined by microscratch tests.Finally,further tests on quartz-and clay-rich samples of the Longmaxi shale suggest further variations in the samples’mechanical properties depending on their burial conditions and the mechanical properties of their dominant mineral phases.展开更多
This study examined the isolation and differentiation of dorsal root ganglion progenitor cells for therapeutic use in neurodegenerative diseases. Rat embryonic dorsal root ganglia progenitors were isolated and purifie...This study examined the isolation and differentiation of dorsal root ganglion progenitor cells for therapeutic use in neurodegenerative diseases. Rat embryonic dorsal root ganglia progenitors were isolated and purified using the differential adhesion method combined with cytosine arabinoside treatment. After culture in serum-free medium supplemented with B27, basic fibroblast growth factor and epidermal growth factor, these cells remained viable and survived for more than 18 months in vitro. Most cells differentiated to neurons that were immunoreactive for gamma-aminobutyric acid and choline acetyltransferase as detected by immunohistochemical staining. In addition, nerve growth factor and neurotrophic tyrosine kinase receptor expression were also observed in dorsal root ganglion progenitors and differentiated cells. K252a, an inhibitor that blocks nerve growth factor-induced signaling, inhibited cell survival, suggesting the possible existence of a nerve growth factor autocrine loop in these proliferating cells.展开更多
In multiple sclerosis(MS),human endogenous retrovirus W family(HERV-W)envelope protein,pHERV-W ENV,limits remyelination and induces microglia-mediated neurodegeneration.To better understand its role,we examined the so...In multiple sclerosis(MS),human endogenous retrovirus W family(HERV-W)envelope protein,pHERV-W ENV,limits remyelination and induces microglia-mediated neurodegeneration.To better understand its role,we examined the soluble pHERV-W antigen from MS brain lesions detected by specific antibodies.Physico-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and syncytin-1.pHERV-W ENV monomers and trimers remained associated with membranes,while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS brain.Extracellular hexamers are stabilized by internal hydrophobic bonds and external hydrophilic moieties.HERV-W studies in MS also suggest that this diffusible antigen may correspond to a previously described highmolecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS pathogenesis.Adapted methods are now needed to identify encoding HERV provirus(es)in affected cells DNA.The properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS pathogenesis.The present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.展开更多
AIM: To test whether the replication of human rhinovirus(HRV) is regulated by micro RNAs in human bronchial epithelial cells.METHODS: For the present study, the human cell line BEAS-2B(derived from normal human bronch...AIM: To test whether the replication of human rhinovirus(HRV) is regulated by micro RNAs in human bronchial epithelial cells.METHODS: For the present study, the human cell line BEAS-2B(derived from normal human bronchial epithelial cells) was adopted. DICER knock-down, by si RNA transfection in BEAS-2B cells, was performed in order to inhibit micro RNA maturation globally. Alternatively, antisense oligonucleotides(anti-mi Rs) were transfectedto inhibit the activity of specific micro RNAs. Cells were infected with HRV-1B. Viral replication was assessed by measuring the genomic viral RNA by reverse transcription quantitative polymerase chain reaction(RT-q PCR). Association between micro RNA-induced-silencing-complex and viral RNA was detected by Ago2 co-immunoprecipitation followed by RT-q PCR. Targetscan v.6 was used to predict micro RNA target sites on several HRV strains.RESULTS: Here, we show that micro RNAs affect replication of HRV-1B. DICER knock-down significantly reduced the expression of mature micro RNAs in a bronchial epithelial cell line(BEAS-2B) and in turn, increased the synthesis of HRV-1B RNA. Additionally, HRV-1B RNA co-immunoprecipitated with argonaute 2 protein, an important effector for micro RNA activity suggesting that micro RNAs bind to viral RNA during infection. In order to identify specific micro RNAs involved in this interaction, we employed bioinformatics analysis, and selected a group of micro RNAs that have been reported to be under-expressed in asthmatic bronchial epithelial cells and were predicted to target different strains of rhinoviruses(HRV-1B,-16,-14,-27). Our results suggest that, out of this group of micro RNAs, mi R-128 and mi R-155 contribute to the innate defense against HRV-1B: transfection of specific anti-mi Rs increased viral replication, as anticipated in-silico.CONCLUSION: Taken together, our results suggest that pathological changes in micro RNA expression, as already reported for asthma or chronic obstructive pulmonary disease have the potential to affect Rhinovirus replication and therefore may play a role in virusinduced exacerbations.展开更多
In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid ...In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.展开更多
The physics of compressible turbulence in high energy density(HED) plasmas is an unchartered experimental area.Simulations of compressible and radiative flows relevant for astrophysics rely mainly on subscale paramete...The physics of compressible turbulence in high energy density(HED) plasmas is an unchartered experimental area.Simulations of compressible and radiative flows relevant for astrophysics rely mainly on subscale parameters. Therefore,we plan to perform turbulent hydrodynamics experiments in HED plasmas(TurboHEDP) in order to improve our understanding of such important phenomena for interest in both communities: laser plasma physics and astrophysics. We will focus on the physics of supernovae remnants which are complex structures subject to fluid instabilities such as the Rayleigh–Taylor and Kelvin–Helmholtz instabilities. The advent of megajoule laser facilities, like the National Ignition Facility and the Laser Megajoule, creates novel opportunities in laboratory astrophysics, as it provides unique platforms to study turbulent mixing flows in HED plasmas. Indeed, the physics requires accelerating targets over larger distances and longer time periods than previously achieved. In a preparatory phase, scaling from experiments at lower laser energies is used to guarantee the performance of future MJ experiments. This subscale experiments allow us to develop experimental skills and numerical tools in this new field of research, and are stepping stones to achieve our objectives on larger laser facilities. We review first in this paper recent advances in high energy density experiments devoted to laboratory astrophysics. Then we describe the necessary steps forward to commission an experimental platform devoted to turbulent hydrodynamics on a megajoule laser facility. Recent novel experimental results acquired on LULI2000, as well as supporting radiative hydrodynamics simulations, are presented. Together with the development of LiF detectors as transformative X-ray diagnostics, these preliminary results are promising on the way to achieve micrometric spatial resolution in turbulent HED physics experiments in the near future.展开更多
We investigate the validity of stationary simulations for semiconductor quantum charge transport in a one-dimensional resonant tunneling diode via fluid type models.Careful numerical investigations to a quantum hydrod...We investigate the validity of stationary simulations for semiconductor quantum charge transport in a one-dimensional resonant tunneling diode via fluid type models.Careful numerical investigations to a quantum hydrodynamic model reveal that the transient simulations do not always converge to the steady states.In particular,growing oscillations are observed at relatively large applied voltage.A dynamical bifurcation is responsible for the stability interchange of the steady state.Transient and stationary computations are also performed for a unipolar quantum drift-diffusion model.展开更多
Severe forms of coronavirus disease 2019(COVID-19)have been associated with a cytokine storm mainly involving interleukin(IL)-6,IL-1β,and TNF.1,2 Several authors have reported features of macrophage activation,thus c...Severe forms of coronavirus disease 2019(COVID-19)have been associated with a cytokine storm mainly involving interleukin(IL)-6,IL-1β,and TNF.1,2 Several authors have reported features of macrophage activation,thus comparing the cytokine storm of COVID-19 to reactive hemophagocytic lymphohistiocytosis(reHLH).3,4 However,these data have been balanced by other studies primarily involving IL-6 and,therefore,a mechanism closer to the complex immune dysregulation observed in sepsis.5,6 Considering these discrepancies,serum cytokine profiling may not be the best option for assessing COVID-19 severity and prognosis.Serum ferritin,an inflammatory biomarker,is elevated in most COVID-19 patients and has been correlated with severity and mortality.展开更多
Bladder cancer(BLCA)is a common malignant tumor of the urinary system,with significant morbidity and mortality rates worldwide.The MEN1 gene,encoding the menin protein,plays a regulatory role in several cancers.Howeve...Bladder cancer(BLCA)is a common malignant tumor of the urinary system,with significant morbidity and mortality rates worldwide.The MEN1 gene,encoding the menin protein,plays a regulatory role in several cancers.However,the role played by menin in BLCA remains elusive.In this study,our data demonstrated that the expression of menin was significantly up-regulated in BLCA tissues versus normal tissues,and the high expression of menin was strongly correlated with poor prognosis of BLCA patients.In vitro,silencing MEN1 inhibited cell proliferation and induced cell cycle arrest at the G1/S phase in BLCA cells.Furthermore,RNA sequencing analysis revealed that MEN1 knockdown significantly inhibited the Wnt/β-catenin signaling in BLCA cells.Meanwhile,we further confirmed thatβ-catenin served as a critical downstream effector of menin in BLCA cells.Mechanically,chromatin immunoprecipitation analysis demonstrated that menin promoted CTNNB1(catenin beta 1)transcription through binding to the CTNNB1 proximal promoter in BLCA cells.Interestingly,menin collaborated with TFAP2C,a regulator ofβ-catenin in BLCA cells,to enhance the transcription of the CTNNB1 gene.More intriguingly,BAY-155,a menin molecule inhibitor,inhibited cell growth of BLCA cells both in vitro and in vivo by suppressing the expression of menin,TFAP2C,andβ-catenin.Our current work unveils an important role of the menin in triggering the TFAP2C/β-catenin axis,which contributes to cell proliferation of BLCA cells.Therefore,menin might be served as a new therapeutic target for BLCA.展开更多
Developing the next plant generation within the seed requires the coordination of complex programs driving pattern formation, growth, and differentiation of the three main seed compartments： the embryo （future plant...Developing the next plant generation within the seed requires the coordination of complex programs driving pattern formation, growth, and differentiation of the three main seed compartments： the embryo （future plant）, the endosperm （storage compartment）, representing the two filial tissues, and the surround- ing maternal tissues. This review focuses on the signaling pathways and molecular players involved in early maize kernel development. In the 2 weeks following pollination, functional tissues are shaped from single cells, readying the kernel for filling with storage compounds. Although the overall picture of the signaling pathways regulating embryo and endosperm development remains fragmentary, several types of molecu- lar actors, such as hormones, sugars, or peptides, have been shown to be involved in particular aspects of these developmental processes. These molecular actors are likely to be components of signaling pathways that lead to transcriptional programming mediated by transcriptional factors. Through the integrated action of these components, multiple types of information received by cells or tissues lead to the correct differentiation and patterning of kernel compartments. In this review, recent advances regarding the four types of molecular actors （hormones, sugars, peptides/receptors, and transcription factors） involved in early maize development are presented.展开更多
Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using eit...Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein(Spike),we studied the neutralizing antibody(nAb)response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections,including patients with mild symptoms and also more severe forms,including those that required intensive care.We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels.Indeed,patients from intensive care units exhibited high nAb titers;conversely,patients with milder disease symptoms had heterogeneous nAb titers,and asymptomatic or exclusive outpatient-care patients had no or low nAbs.We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses.Moreover,we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2,indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2.Finally,we found that the D614G mutation in the spike protein,which has recently been identified as the current major variant in Europe,does not allow neutralization escape.Altogether,our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease,and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.展开更多
Auxin is a key hormone performing a wealth of functions throughout the life cycle of plants. It acts largely by regulating genes at the transcriptional level through a family of transcription factors called auxin resp...Auxin is a key hormone performing a wealth of functions throughout the life cycle of plants. It acts largely by regulating genes at the transcriptional level through a family of transcription factors called auxin response factors (ARFs). Even though all ARF monomers analyzed so far bind a similar DNA sequence, there is evidence that ARFs differ in their target genomic regions and regulated genes. Here, we report the use of position weight matrices (PWMs) to model ARF DNA binding specificity based on published DNA affinity purification sequencing (DAP-seq) data. We found that the genome binding of two ARFs (ARF2 and ARF5/ Monopteros [MP]) differ largely because these two factors have different preferred ARF binding site (ARFbs) arrangements (orientation and spacing). We illustrated why PWMs are more versatile to reliably identify ARFbs than the widely used consensus sequences and demonstrated their power with biochemical experiments in the identification of the regulatory regions o1IAA19, an well-characterized auxin-responsive gene. Finally, we combined gene regulation by auxin with ARF-bound regions and identified specific ARFbs configurations that are over-represented in auxin-upregulated genes, thus deciphering the ARFbs syntax functional for regulation. Our study provides a general method to exploit the potential of genome-wide DNA binding assays and to decode gene regulation.展开更多
Pioneer transcription factors(TFs)are a special category of TFs with the capacity to bind to closed chromatin regions in which DNA is wrapped around histones and may be highly methylated.Subsequently,pioneer TFs are a...Pioneer transcription factors(TFs)are a special category of TFs with the capacity to bind to closed chromatin regions in which DNA is wrapped around histones and may be highly methylated.Subsequently,pioneer TFs are able to modify the chromatin state to initiate gene expression.In plants,LEAFY(LFY)is a master floral regulator and has been suggested to act as a pioneer TF in Arabidopsis.Here,we demonstrate that LFY is able to bind both methylated and non-methylated DNA using a combination of in vitro genomewide binding experiments and structural modeling.Comparisons between regions bound by LFY in vivo and chromatin accessibility data suggest that a subset of LFY bound regions is occupied by nucleosomes.We confirm that LFY is able to bind nucleosomal DNA in vitro using reconstituted nucleosomes.Finally,we show that constitutive LFY expression in seedling tissues is sufficient to induce chromatin accessibility in the LFY direct target genes APETALA1 and AGAMOUS.Taken together,our study suggests that LFY possesses key pioneer TF features that contribute to launching the floral gene expression program.展开更多
The roots of hyperbolic polynomials satisfy the linear inequalities that were previously established for the eigenvalues of Hermitian matrices,after a conjecture by A.Horn.Among them are the so-called Weyl and Lidski...The roots of hyperbolic polynomials satisfy the linear inequalities that were previously established for the eigenvalues of Hermitian matrices,after a conjecture by A.Horn.Among them are the so-called Weyl and Lidskiǐ inequalities.An elementary proof of the latter for hyperbolic polynomials is given.This proof follows an idea from H.Weinberger and is free from representation theory and Schubert calculus arguments,as well as from hyperbolic partial differential equations theory.展开更多
The diffraction of a dielectric microline pair is optimized by numerical simulations to generate an efficient focusing pattern with a micron-scale footprint. Microlines separated by 1.12 μm are fabricated by two-phot...The diffraction of a dielectric microline pair is optimized by numerical simulations to generate an efficient focusing pattern with a micron-scale footprint. Microlines separated by 1.12 μm are fabricated by two-photon polymerization on a glass substrate, and their diffraction pattern is characterized by three-dimensional wide-field transmission microscopy. A line pair, having a width W=0.40 μm and a height H=0.80 μm, leads to diffraction-limited focusing in the visible spectrum. Depending on wavelength, its focal length, lateral resolution,and depth of focus are in the ranges of 0.8–1.3 μm, 0.22–0.44 μm, and 1.7–2.13μm, respectively. Such a microlens based on the diffraction of only two subwavelength scatterers could be used for the design of miniature optical sensors with micron and sub-micron pixels.展开更多
Mass renovation goals aimed at energy savings on a national scale require a significant level of public financial commitment.To identify target buildings,decision-makers need a thorough understanding of energy perform...Mass renovation goals aimed at energy savings on a national scale require a significant level of public financial commitment.To identify target buildings,decision-makers need a thorough understanding of energy performance.Energy Performance Certificates(EPC)provide information about areas of space,such as land plots or a building’s footprint,without specifying exact locations.They cover only a fraction of dwellings.This paper demonstrates that learning from observed EPCs to predict missing ones at the building level can be viewed as a spatial interpolation problem with uncertainty both on input and output variables.The Kriging methodology is applied to random fields observed at random locations to determine the Best Linear Unbiased Predictor(BLUP).Although the Gaussian setting is lost,conditional moments can still be derived.Covariates are admissible,even with missing observations.We present applications using both simulated and real data,with a specific case study of a city in France serving as an example.展开更多
基金supported by the NSF of China(Grant No.41520104004)。
文摘Knowing the phase relations of carbon-bearing phases at high-pressure(HP) and high-temperature(HT) condition is essential for understanding the deep carbon cycle in the subduction zones.In particular,the phase relation of carbon-bearing phases is also strongly influenced by redox condition of subduction zones,which is poorly explored.Here we summarized the phase relations of carbon-bearing phases(calcite,aragonite,dolomite,magnesite,graphite,hydrocarbon) in HP metamorphic rocks(marble,metapelite,eclogite) from the Western Tianshan subduction zone and high-pressure experiments.During prograde progress of subduction,carbonates in altered oceanic crust change from Ca-carbonate(calcite) to Ca,Mg-carbonate(dolomite),then finally to Mgcarbonate(magnesite) via Mg-Ca cation exchange reaction between silicate and carbonate,while calcite in sedimentary calcareous ooze on oceanic crust directly transfers to high-pressure aragonite in marble or amorphous CaCO3 in subduction zones.Redox evolution also plays a significant effect on the carbon speciation in the Western Tianshan subduction zone.The prograde oxygen fugacity of the Western Tianshan subduction zone was constrained by mineral assemblage of garnet-omphacite from FMQ-1.9 to FMQ-2.5 at its metamorphic peak(maximum P-T) conditions.In comparison with redox conditions of other subduction zones,Western Tianshan has the lowest oxygen fugacity.Graphite and light hydrocarbon inclusions were ubiqutously identified in Western Tianshan HP metamorphic rocks and speculated to be formed from reduction of Fe-carbonate at low redox condition,which is also confirmed by high-pressure experimental simulation.Based on petrological observation and high-pressure simulation,a polarized redox model of reducing slab but oxidizing mantle wedge in subduction zone is proposed,and its effect on deep carbon cycle in subduction zones is further discussed.
文摘Semen from 10 932 male partners of infertile couples was analysed and sperm parameter trends were evaluated at the Reproduction Biology Laboratory of the University Hospital of Marseille （France） between 1988 and 2007. After 3-6 days of abstinence, semen samples were collected. Measurements of seminal fluid volume, pH, sperm concentration, total sperm count, motility and detailed morphology of spermatozoa were performed. Sperm parameters were analysed on the entire population and in men with normal total numeration （ 〉~ 40 million per ejaculate）. The whole population demonstrated declining trends in sperm concentration （1.5% per year）, total sperm count （1.6% per year）, total motility （0.4% per year）, rapid motility （5.5% per year） and normal morphology （2.2% per year）. In the group of selected samples with total normal sperm count, the same trends of sperm quality deterioration with time were observed. Our results clearly indicate that the auality of semen decreased in this population over the study period.
基金This research was funded by the National Natural Science Foundation of China(Project Nos.51979144 and 51661165015)State Key Laboratory of Hydroscience and Engineering(Open Research Fund Program 2019-D-03).
文摘Mechanical properties,such as the hardness H,Young’s modulus E,creep modulus C,and fracture toughness Kc,are essential parameters in the design of hydraulic fracturing systems for prospective shale gas formations.In this study,a practical methodology is presented for obtaining these properties through microindentation experiments combined with quantitative observations of the mineralogical phases using X-ray diffraction(XRD),scanning electron microscopy(SEM)with backscattered electron(BSE)imaging,and energy-dispersive X-ray spectroscopy(EDS)analyses.We apply this method in the case of three types of Longmaxi shales with different mineralogies(i.e.carbonate-,clay-,and quartz-rich,respectively),which allows us to determine the characteristic indentation depth,hc?8e10 mm,beyond which the mechanical response of the carbonate-rich shale is homogeneous and independent of its complex heterogeneous microstructure.Moreover,exploiting the results of a large number of indentation tests,we demonstrate that the indentation modulus M of the shale increases as a power-law of hardness H,and its creep modulus C increases linearly with H.We also compute the fracture toughness Kc from the indentation data by assuming a perfectly plastic behavior of the sample.Our results are in good agreement with independent measurements of Kc determined by microscratch tests.Finally,further tests on quartz-and clay-rich samples of the Longmaxi shale suggest further variations in the samples’mechanical properties depending on their burial conditions and the mechanical properties of their dominant mineral phases.
基金supported by the Rhone Alps Region of France, MIRA grants for the collaboration,the Agence National de la Recherche (ANR) RIB,the CNRS (International program for Scientific Cooperation, "PICS")
文摘This study examined the isolation and differentiation of dorsal root ganglion progenitor cells for therapeutic use in neurodegenerative diseases. Rat embryonic dorsal root ganglia progenitors were isolated and purified using the differential adhesion method combined with cytosine arabinoside treatment. After culture in serum-free medium supplemented with B27, basic fibroblast growth factor and epidermal growth factor, these cells remained viable and survived for more than 18 months in vitro. Most cells differentiated to neurons that were immunoreactive for gamma-aminobutyric acid and choline acetyltransferase as detected by immunohistochemical staining. In addition, nerve growth factor and neurotrophic tyrosine kinase receptor expression were also observed in dorsal root ganglion progenitors and differentiated cells. K252a, an inhibitor that blocks nerve growth factor-induced signaling, inhibited cell survival, suggesting the possible existence of a nerve growth factor autocrine loop in these proliferating cells.
文摘In multiple sclerosis(MS),human endogenous retrovirus W family(HERV-W)envelope protein,pHERV-W ENV,limits remyelination and induces microglia-mediated neurodegeneration.To better understand its role,we examined the soluble pHERV-W antigen from MS brain lesions detected by specific antibodies.Physico-chemical and antigenic characteristics confirmed differences between pHERV-W ENV and syncytin-1.pHERV-W ENV monomers and trimers remained associated with membranes,while hexamers self-assembled from monomers into a soluble macrostructure involving sulfatides in MS brain.Extracellular hexamers are stabilized by internal hydrophobic bonds and external hydrophilic moieties.HERV-W studies in MS also suggest that this diffusible antigen may correspond to a previously described highmolecular-weight neurotoxic factor secreted by MS B-cells and thus represents a major agonist in MS pathogenesis.Adapted methods are now needed to identify encoding HERV provirus(es)in affected cells DNA.The properties and origin of MS brain pHERV-W ENV soluble antigen will allow a better understanding of the role of HERVs in MS pathogenesis.The present results anyhow pave the way to an accurate detection of the different forms of pHERV-W ENV antigen with appropriate conditions that remained unseen until now.
基金Supported by MRC,AAIR and the Roger Brooke charitable trust
文摘AIM: To test whether the replication of human rhinovirus(HRV) is regulated by micro RNAs in human bronchial epithelial cells.METHODS: For the present study, the human cell line BEAS-2B(derived from normal human bronchial epithelial cells) was adopted. DICER knock-down, by si RNA transfection in BEAS-2B cells, was performed in order to inhibit micro RNA maturation globally. Alternatively, antisense oligonucleotides(anti-mi Rs) were transfectedto inhibit the activity of specific micro RNAs. Cells were infected with HRV-1B. Viral replication was assessed by measuring the genomic viral RNA by reverse transcription quantitative polymerase chain reaction(RT-q PCR). Association between micro RNA-induced-silencing-complex and viral RNA was detected by Ago2 co-immunoprecipitation followed by RT-q PCR. Targetscan v.6 was used to predict micro RNA target sites on several HRV strains.RESULTS: Here, we show that micro RNAs affect replication of HRV-1B. DICER knock-down significantly reduced the expression of mature micro RNAs in a bronchial epithelial cell line(BEAS-2B) and in turn, increased the synthesis of HRV-1B RNA. Additionally, HRV-1B RNA co-immunoprecipitated with argonaute 2 protein, an important effector for micro RNA activity suggesting that micro RNAs bind to viral RNA during infection. In order to identify specific micro RNAs involved in this interaction, we employed bioinformatics analysis, and selected a group of micro RNAs that have been reported to be under-expressed in asthmatic bronchial epithelial cells and were predicted to target different strains of rhinoviruses(HRV-1B,-16,-14,-27). Our results suggest that, out of this group of micro RNAs, mi R-128 and mi R-155 contribute to the innate defense against HRV-1B: transfection of specific anti-mi Rs increased viral replication, as anticipated in-silico.CONCLUSION: Taken together, our results suggest that pathological changes in micro RNA expression, as already reported for asthma or chronic obstructive pulmonary disease have the potential to affect Rhinovirus replication and therefore may play a role in virusinduced exacerbations.
文摘In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.
基金supported by the Agence Nationale de la Recherche under the ANR project TurboHEDP(ANR-15-CE30-0011)
文摘The physics of compressible turbulence in high energy density(HED) plasmas is an unchartered experimental area.Simulations of compressible and radiative flows relevant for astrophysics rely mainly on subscale parameters. Therefore,we plan to perform turbulent hydrodynamics experiments in HED plasmas(TurboHEDP) in order to improve our understanding of such important phenomena for interest in both communities: laser plasma physics and astrophysics. We will focus on the physics of supernovae remnants which are complex structures subject to fluid instabilities such as the Rayleigh–Taylor and Kelvin–Helmholtz instabilities. The advent of megajoule laser facilities, like the National Ignition Facility and the Laser Megajoule, creates novel opportunities in laboratory astrophysics, as it provides unique platforms to study turbulent mixing flows in HED plasmas. Indeed, the physics requires accelerating targets over larger distances and longer time periods than previously achieved. In a preparatory phase, scaling from experiments at lower laser energies is used to guarantee the performance of future MJ experiments. This subscale experiments allow us to develop experimental skills and numerical tools in this new field of research, and are stepping stones to achieve our objectives on larger laser facilities. We review first in this paper recent advances in high energy density experiments devoted to laboratory astrophysics. Then we describe the necessary steps forward to commission an experimental platform devoted to turbulent hydrodynamics on a megajoule laser facility. Recent novel experimental results acquired on LULI2000, as well as supporting radiative hydrodynamics simulations, are presented. Together with the development of LiF detectors as transformative X-ray diagnostics, these preliminary results are promising on the way to achieve micrometric spatial resolution in turbulent HED physics experiments in the near future.
基金This research is partially supported by NSFC under grant No.90407021National Basic Research Pro-gram of China under contract number 2007CB814800the China Ministry of Educa-tion under contract number NCET-06-0011.
文摘We investigate the validity of stationary simulations for semiconductor quantum charge transport in a one-dimensional resonant tunneling diode via fluid type models.Careful numerical investigations to a quantum hydrodynamic model reveal that the transient simulations do not always converge to the steady states.In particular,growing oscillations are observed at relatively large applied voltage.A dynamical bifurcation is responsible for the stability interchange of the steady state.Transient and stationary computations are also performed for a unipolar quantum drift-diffusion model.
文摘Severe forms of coronavirus disease 2019(COVID-19)have been associated with a cytokine storm mainly involving interleukin(IL)-6,IL-1β,and TNF.1,2 Several authors have reported features of macrophage activation,thus comparing the cytokine storm of COVID-19 to reactive hemophagocytic lymphohistiocytosis(reHLH).3,4 However,these data have been balanced by other studies primarily involving IL-6 and,therefore,a mechanism closer to the complex immune dysregulation observed in sepsis.5,6 Considering these discrepancies,serum cytokine profiling may not be the best option for assessing COVID-19 severity and prognosis.Serum ferritin,an inflammatory biomarker,is elevated in most COVID-19 patients and has been correlated with severity and mortality.
基金supported by the National Key Research and Development Program of China(No.2022YFA1205704)the Natural Science Foundation of Heilongjiang Province,China(No.YQ2023H015)+2 种基金the Fundamental Research Funds for the Provincial Universities of Heilongjiang,China(No.2022KYYWF-0298)the Research Fund of the Fourth Affiliated Hospital of Harbin Medical University(No.HYDSYRCYJ02)the Research Fund of Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal in Three Gorges Reservoir Area(China)(No.KFKT2022011).
文摘Bladder cancer(BLCA)is a common malignant tumor of the urinary system,with significant morbidity and mortality rates worldwide.The MEN1 gene,encoding the menin protein,plays a regulatory role in several cancers.However,the role played by menin in BLCA remains elusive.In this study,our data demonstrated that the expression of menin was significantly up-regulated in BLCA tissues versus normal tissues,and the high expression of menin was strongly correlated with poor prognosis of BLCA patients.In vitro,silencing MEN1 inhibited cell proliferation and induced cell cycle arrest at the G1/S phase in BLCA cells.Furthermore,RNA sequencing analysis revealed that MEN1 knockdown significantly inhibited the Wnt/β-catenin signaling in BLCA cells.Meanwhile,we further confirmed thatβ-catenin served as a critical downstream effector of menin in BLCA cells.Mechanically,chromatin immunoprecipitation analysis demonstrated that menin promoted CTNNB1(catenin beta 1)transcription through binding to the CTNNB1 proximal promoter in BLCA cells.Interestingly,menin collaborated with TFAP2C,a regulator ofβ-catenin in BLCA cells,to enhance the transcription of the CTNNB1 gene.More intriguingly,BAY-155,a menin molecule inhibitor,inhibited cell growth of BLCA cells both in vitro and in vivo by suppressing the expression of menin,TFAP2C,andβ-catenin.Our current work unveils an important role of the menin in triggering the TFAP2C/β-catenin axis,which contributes to cell proliferation of BLCA cells.Therefore,menin might be served as a new therapeutic target for BLCA.
文摘Developing the next plant generation within the seed requires the coordination of complex programs driving pattern formation, growth, and differentiation of the three main seed compartments： the embryo （future plant）, the endosperm （storage compartment）, representing the two filial tissues, and the surround- ing maternal tissues. This review focuses on the signaling pathways and molecular players involved in early maize kernel development. In the 2 weeks following pollination, functional tissues are shaped from single cells, readying the kernel for filling with storage compounds. Although the overall picture of the signaling pathways regulating embryo and endosperm development remains fragmentary, several types of molecu- lar actors, such as hormones, sugars, or peptides, have been shown to be involved in particular aspects of these developmental processes. These molecular actors are likely to be components of signaling pathways that lead to transcriptional programming mediated by transcriptional factors. Through the integrated action of these components, multiple types of information received by cells or tissues lead to the correct differentiation and patterning of kernel compartments. In this review, recent advances regarding the four types of molecular actors （hormones, sugars, peptides/receptors, and transcription factors） involved in early maize development are presented.
基金The laboratory of FLC received financial support from the LabEx Ecofect(ANR-11-LABX-0048)the“Universitéde Lyon,”within the program“Investissements d’Avenir”(ANR-11-IDEX-0007)+1 种基金operated by the French National Research Agency(ANR),the ANR(grant from RA-Covid-19)the Fondation pour la Recherche Médicale(FRM),and Inserm Transfert.We thank D.Lavillette for providing the SARS-CoV-2 spike expression vector and B.La Scola for providing a clone of Vero-E6 cells.We acknowledge the contribution of SFR Biosciences(UMS3444/CNRS,US8/Inserm,ENS de Lyon,UCBL)ANIRA-Cytometry facility for excellent technical assistance and support.
文摘Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein(Spike),we studied the neutralizing antibody(nAb)response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections,including patients with mild symptoms and also more severe forms,including those that required intensive care.We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels.Indeed,patients from intensive care units exhibited high nAb titers;conversely,patients with milder disease symptoms had heterogeneous nAb titers,and asymptomatic or exclusive outpatient-care patients had no or low nAbs.We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses.Moreover,we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2,indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2.Finally,we found that the D614G mutation in the spike protein,which has recently been identified as the current major variant in Europe,does not allow neutralization escape.Altogether,our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease,and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.
文摘Auxin is a key hormone performing a wealth of functions throughout the life cycle of plants. It acts largely by regulating genes at the transcriptional level through a family of transcription factors called auxin response factors (ARFs). Even though all ARF monomers analyzed so far bind a similar DNA sequence, there is evidence that ARFs differ in their target genomic regions and regulated genes. Here, we report the use of position weight matrices (PWMs) to model ARF DNA binding specificity based on published DNA affinity purification sequencing (DAP-seq) data. We found that the genome binding of two ARFs (ARF2 and ARF5/ Monopteros [MP]) differ largely because these two factors have different preferred ARF binding site (ARFbs) arrangements (orientation and spacing). We illustrated why PWMs are more versatile to reliably identify ARFbs than the widely used consensus sequences and demonstrated their power with biochemical experiments in the identification of the regulatory regions o1IAA19, an well-characterized auxin-responsive gene. Finally, we combined gene regulation by auxin with ARF-bound regions and identified specific ARFbs configurations that are over-represented in auxin-upregulated genes, thus deciphering the ARFbs syntax functional for regulation. Our study provides a general method to exploit the potential of genome-wide DNA binding assays and to decode gene regulation.
基金supported by the ANR-DFG project Flopinet(ANR-16-CE92-0023-01)to C.Z.and F.P.,and GRALa program from the Chemistry Biology Health(CBH)Graduate School of University Grenoble Alpes(ANR-17-EURE-0003)to C.Z.,F.P.,and A.S.
文摘Pioneer transcription factors(TFs)are a special category of TFs with the capacity to bind to closed chromatin regions in which DNA is wrapped around histones and may be highly methylated.Subsequently,pioneer TFs are able to modify the chromatin state to initiate gene expression.In plants,LEAFY(LFY)is a master floral regulator and has been suggested to act as a pioneer TF in Arabidopsis.Here,we demonstrate that LFY is able to bind both methylated and non-methylated DNA using a combination of in vitro genomewide binding experiments and structural modeling.Comparisons between regions bound by LFY in vivo and chromatin accessibility data suggest that a subset of LFY bound regions is occupied by nucleosomes.We confirm that LFY is able to bind nucleosomal DNA in vitro using reconstituted nucleosomes.Finally,we show that constitutive LFY expression in seedling tissues is sufficient to induce chromatin accessibility in the LFY direct target genes APETALA1 and AGAMOUS.Taken together,our study suggests that LFY possesses key pioneer TF features that contribute to launching the floral gene expression program.
文摘The roots of hyperbolic polynomials satisfy the linear inequalities that were previously established for the eigenvalues of Hermitian matrices,after a conjecture by A.Horn.Among them are the so-called Weyl and Lidskiǐ inequalities.An elementary proof of the latter for hyperbolic polynomials is given.This proof follows an idea from H.Weinberger and is free from representation theory and Schubert calculus arguments,as well as from hyperbolic partial differential equations theory.
文摘The diffraction of a dielectric microline pair is optimized by numerical simulations to generate an efficient focusing pattern with a micron-scale footprint. Microlines separated by 1.12 μm are fabricated by two-photon polymerization on a glass substrate, and their diffraction pattern is characterized by three-dimensional wide-field transmission microscopy. A line pair, having a width W=0.40 μm and a height H=0.80 μm, leads to diffraction-limited focusing in the visible spectrum. Depending on wavelength, its focal length, lateral resolution,and depth of focus are in the ranges of 0.8–1.3 μm, 0.22–0.44 μm, and 1.7–2.13μm, respectively. Such a microlens based on the diffraction of only two subwavelength scatterers could be used for the design of miniature optical sensors with micron and sub-micron pixels.
文摘Mass renovation goals aimed at energy savings on a national scale require a significant level of public financial commitment.To identify target buildings,decision-makers need a thorough understanding of energy performance.Energy Performance Certificates(EPC)provide information about areas of space,such as land plots or a building’s footprint,without specifying exact locations.They cover only a fraction of dwellings.This paper demonstrates that learning from observed EPCs to predict missing ones at the building level can be viewed as a spatial interpolation problem with uncertainty both on input and output variables.The Kriging methodology is applied to random fields observed at random locations to determine the Best Linear Unbiased Predictor(BLUP).Although the Gaussian setting is lost,conditional moments can still be derived.Covariates are admissible,even with missing observations.We present applications using both simulated and real data,with a specific case study of a city in France serving as an example.
