scholarly journals Spreading of porous vesicles subjected to osmotic shocks: the role of aquaporins

Soft Matter ◽  
2016 ◽  
Vol 12 (5) ◽  
pp. 1601-1609 ◽  
Author(s):  
Alice Berthaud ◽  
François Quemeneur ◽  
Maxime Deforet ◽  
Patricia Bassereau ◽  
Françoise Brochard-Wyart ◽  
...  
Keyword(s):  
Water Permeability ◽  
Lipid Membranes ◽  
Transmembrane Protein ◽  
New Method ◽  
Eye Lens ◽  
Water Pore

Aquaporin 0 (AQP0) is a transmembrane protein specific to the eye lens, involved as a water carrier across the lipid membranes. We propose here a new method based on GUV spreading to measure the water permeability of membrane and single functional water pore. We also demonstrate that truncated AQP0 do not conduct water.

Children’s Lives and Deaths in Merovingian Gaul

2020 ◽  
pp. 185-213
Author(s):  
Émilie Perez
Keyword(s):  
Social Identity ◽  
Age Groups ◽  
New Method ◽  
Recent Analysis ◽  
Age And Gender ◽  
The Past ◽  
And Gender ◽  
Grave Goods

The role of children in Merovingian society has long been downplayed, and the study of their graves and bones has long been neglected. However, during the past fifteen years, archaeologists have shown growing interest in the place of children in Merovingian society. Nonetheless, this research has not been without challenges linked to the nature of the biological and material remains. Recent analysis of 315 children’s graves from four Merovingian cemeteries in northern Gaul (sixth to seventh centuries) allows us to understand the modalities of burial ritual for children. A new method for classifying children into social age groups shows that the type, quality, quantity, and diversity of grave goods were directly correlated with the age of the deceased. They increased from the age of eight and particularly around the time of puberty. This study discusses the role of age and gender in the construction and expression of social identity during childhood in the Merovingian period.

Inhibition of the water channel aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Montiel ◽  
R Bella ◽  
L Michel ◽  
E Robinson ◽  
J.C Jonas ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cardiac Hypertrophy ◽  
Cardiac Myocytes ◽  
Cardiac Remodeling ◽  
Cardiac Myocyte ◽  
Water Channel ◽  
Transmembrane Transport ◽  
Funding Source ◽  
Water Pore

Abstract Background Pathological remodeling of the myocardium has long been known to involve oxidant signaling, but so far, strategies using systemic anti-oxidants have generally failed to prevent it. Aquaporins are a family of transmembrane water channels with thirteen isoforms currently known. Some isoforms have been implicated in oxidant signaling. AQP1 is the most abundant aquaporin in cardiovascular tissues but its specific role in cardiac remodeling remains unknown. Purpose We tested the role of AQP1 as a key regulator of oxidant-mediated cardiac remodeling amenable to targeted pharmacological therapy. Methods We used mice with genetic deletion of Aqp1 (and wild-type littermate), as well as primary isolates from the same mice and human iPSC/Engineered Heart Tissue to test the role of AQP1 in pro-hypertrophic signaling. Human cardiac myocyte-specific (PCM1+) expression of AQP's and genes involved in hypertrophic remodeling was studied by RNAseq and bioinformatic GO pathway analysis. Results RNA sequencing from human cardiac myocytes revealed that the archetypal AQP1 is a major isoform. AQP1 expression correlates with the severity of hypertrophic remodeling in patients with aortic stenosis. The AQP1 channel was detected at the plasma membrane of human and mouse cardiac myocytes from hypertrophic hearts, where it colocalizes with the NADPH oxidase-2 (NOX2) and caveolin-3. We show that hydrogen peroxide (H2O2), produced extracellularly, is necessary for the hypertrophic response of isolated cardiac myocytes and that AQP1 facilitates the transmembrane transport of H2O2 through its water pore, resulting in activation of oxidant-sensitive kinases in cardiac myocytes. Structural analysis of the amino acid residues lining the water pore of AQP1 supports its permeation by H2O2. Deletion of Aqp1 or selective blockade of AQP1 intra-subunit pore (with Bacopaside II) inhibits H2O2 transport in mouse and human cells and rescues the myocyte hypertrophy in human induced pluripotent stem cell-derived engineered heart muscle. This protective effect is due to loss of transmembrane transport of H2O2, but not water, through the intra-subunit pore of AQP1. Treatment of mice with clinically-approved Bacopaside extract (CDRI08) inhibitor of AQP1 attenuates cardiac hypertrophy and fibrosis. Conclusion We provide the first demonstration that AQP1 functions as an aqua-peroxiporin in primary rodent and human cardiac parenchymal cells. We show that cardiac hypertrophy is mediated by the transmembrane transport of H2O2 through the AQP1 water channel. Our studies open the way to complement the therapeutic armamentarium with specific blockers of AQP1 for the prevention of adverse remodeling in many cardiovascular diseases leading to heart failure. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FRS-FNRS, Welbio

scholarly journals Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

2021 ◽  
Vol 22 (5) ◽  
pp. 2732
Author(s):  
Nadine Reichhart ◽  
Vladimir M. Milenkovic ◽  
Christian H. Wetzel ◽  
Olaf Strauß
Keyword(s):  
Transmembrane Protein ◽  
Functional Characterization ◽  
Missense Mutations ◽  
Mutant Proteins ◽  
Functional Consequences ◽  
New Perspective ◽  
The Stability ◽  
Dynamics Simulations ◽  
And Function

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca2+-dependent ion channels and/or Ca2+-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.

scholarly journals A new method for identifying the role of marital preferences at shaping marriage patterns

2021 ◽  
pp. 1-27
Author(s):  
Anna Naszodi ◽  
Francisco Mendonca
Keyword(s):  
Contingency Table ◽  
Transformation Method ◽  
New Method ◽  
Marriage Patterns ◽  
The Us ◽  
Analytical Properties ◽  
The Matrix ◽  
Transformation Methods

Abstract We develop a method which assumes that marital preferences are characterized either by the scalar-valued measure proposed by Liu and Lu, or by the matrix-valued generalized Liu–Lu measure. The new method transforms an observed contingency table into a counterfactual table while preserving its (generalized) Liu–Lu value. After exploring some analytical properties of the new method, we illustrate its application by decomposing changes in the prevalence of homogamy in the US between 1980 and 2010. We perform this decomposition with two alternative transformation methods as well where both methods capture preferences differently from Liu and Lu. Finally, we use survey evidence to support our claim that out of the three considered methods, the new transformation method is the most suitable for identifying the role of marital preferences at shaping marriage patterns. These data are also in favor of measuring assortativity in preferences à la Liu and Lu.

scholarly journals Spin-label saturation-recovery EPR at W-band: Applications to eye lens lipid membranes

2011 ◽  
Author(s):  
Laxman Mainali ◽  
Marija Raguz ◽  
Theodore G. Camenisch ◽  
James S. Hyde ◽  
Witold K. Subczynski
Keyword(s):  
Spin Label ◽  
Lipid Membranes ◽  
Saturation Recovery ◽  
Eye Lens ◽  
W Band

scholarly journals Characterizing Highly Benefited Patients in Randomized Clinical Trials

2017 ◽  
Vol 13 (1) ◽  
Author(s):  
Vivek Charu ◽  
Paul B. Rosenberg ◽  
Lon S. Schneider ◽  
Lea T. Drye ◽  
Lisa Rein ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Controlled Trial ◽  
New Method ◽  
Usual Model ◽  
Randomized Controlled ◽  
Working Model ◽  
Large Numbers ◽  
High Benefit ◽  
Two Stages

AbstractPhysicians and patients may choose a certain treatment only if it is predicted to have a large effect for the profile of that patient. We consider randomized controlled trials in which the clinical goal is to identify as many patients as possible that can highly benefit from the treatment. This is challenging with large numbers of covariate profiles, first, because the theoretical, exact method is not feasible, and, second, because usual model-based methods typically give incorrect results. Better, more recent methods use a two-stage approach, where a first stage estimates a working model to produce a scalar predictor of the treatment effect for each covariate profile; and a second stage estimates empirically a high-benefit group based on the first-stage predictor. The problem with these methods is that each of the two stages is usually agnostic about the role of the other one in addressing the clinical goal. We propose a method that characterizes highly benefited patients by linking model estimation directly to the particular clinical goal. It is shown that the new method has the following two key properties in comparison with existing approaches: first, the meaning of the solution with regard to the clinical goal is the same, and second, the value of the solution is the best that can be achieved when using the working model as a predictor, even if that model is incorrect. In the Citalopram for Agitation in Alzheimer’s Disease (CitAD) randomized controlled trial, the new method identifies substantially larger groups of highly benefited patients, many of whom are missed by the standard method.

The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

2021 ◽  
Author(s):  
Diana Hamdan ◽  
Lisa A. Robinson
Keyword(s):  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transmembrane Protein ◽  
Soluble Form ◽  
Protective Effects ◽  
Chronic Kidney Diseases ◽  
The Family ◽  
Soluble Species ◽  
And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

PIN-FORMED 1 regulates cell fate at the periphery of the shoot apical meristem

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5157-5165 ◽  
Author(s):  
T. Vernoux ◽  
J. Kronenberger ◽  
O. Grandjean ◽  
P. Laufs ◽  
J. Traas
Keyword(s):  
Cell Fate ◽  
Apical Meristem ◽  
Transmembrane Protein ◽  
Loss Of Function ◽  
Hybrid Identity ◽  
Hormone Transport ◽  
Early Markers ◽  
Ideal Tool ◽  
And Function

The process of organ positioning has been addressed, using the pin-formed 1 (pin1) mutant as a tool. PIN1 is a transmembrane protein involved in auxin transport in Arabidopsis. Loss of function severely affects organ initiation, and pin1 mutants are characterised by an inflorescence meristem that does not initiate any flowers, resulting in the formation of a naked inflorescence stem. This phenotype, combined with the proposed role of PIN1 in hormone transport, makes the mutant an ideal tool to study organ formation and phyllotaxis, and here we present a detailed analysis of the molecular modifications at the shoot apex caused by the mutation. We show that meristem structure and function are not severely affected in the mutant. Major alterations, however, are observed at the periphery of the pin1 meristem, where organ initiation should occur. Although two very early markers of organ initiation, LEAFY and AINTEGUMENTA, are expressed at the periphery of the mutant meristem, the cells are not recruited into distinct primordia. Instead a ring-like domain expressing those primordium specific genes is observed around the meristem. This ring-like domain also expresses a boundary marker, CUP-SHAPED COTYLEDON 2, involved in organ separation, showing that the zone at the meristem periphery has a hybrid identity. This implies that PIN1 is not only involved in organ outgrowth, but that it is also necessary for organ separation and positioning. A model is presented in which PIN1 and the local distribution of auxin control phyllotaxis.

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