Papers by Cristobal dos Remedios
The Journal of Physiology, Jun 1, 1991
I To whom correspondence and reprint requests should be addressed. MS 8321 41T. J. WILSON AND OTH... more I To whom correspondence and reprint requests should be addressed. MS 8321 41T. J. WILSON AND OTHERS carried out with recombined mvofibrillar proteins which had been previously reacted with DTNB it was found that modification of myosin, but not modification of thin filament proteins, led to changes in the superprecipitation reaction. 7. Both the skinned fibre results and the superprecipitation results indicate that the effects of DTNB upon the fibre characteristics are primarily due to modifications of the sulphydryl groups of myosin. Therefore, these results show that myosin is not only involved in determining the ability of the contractile apparatus to develop force but also in determining the Ca2+-regulatory characteristics of the muscle fibre.
Biophysical Reviews, Sep 24, 2018
This issue contains 20 articles from contributors at the joint symposium of the Australian Societ... more This issue contains 20 articles from contributors at the joint symposium of the Australian Society for Biophysics (ASB) and the Biophysical Society of Japan (BSJ) held at the University of Technology Sydney in November 27-29, 2017. For a small society, the ASB regularly Bpunches^above its weight. The next meeting of the ASB will again be a joint conference, this time in conjunction with the Asian Biophysics Association to be held in Melbourne December 2-6, 2018 at the University of Melbourne. The programmed symposium themes will include Biophysics and Medicine, Membrane Biophysics, Structural Biology, Nanobiophysics, and Imaging and Super-resolution Microscopy.
Biophysical Reviews, Jan 13, 2018
In 2017, a Special Issue of Biophysical Reviews was devoted to BTitin and Its Binding Partners. T... more In 2017, a Special Issue of Biophysical Reviews was devoted to BTitin and Its Binding Partners. The issue contained a review: BAn historical perspective of the discovery of titin filaments^by dos Remedios and Gilmour that was intended to be a history of the discovery of the giant protein titin, previously named connectin. The review took readers back to the earliest discovery of the so-called third filament component of skeletal and cardiac muscle sarcomeres and ended in 1969. Recently, my colleague Shin'ichi Ishiwata gently reminded me of two papers published in 1990 and 1993 that were unwittingly omitted from the original historical perspective. In the first paper (J Cell Biol 110:53-62, 1990), Funatsu et al. examined the elastic filaments in skeletal muscle using a combination of light and electron microscopy, but they also measured resting as well as passive stiffness mechanical measurements to establish that connectin (titin) is responsible for both stiffness and fiber tension. In the second paper (J Cell Biol 120:711-724, 1993), Funatsu et al. used permeabilised cardiac muscle myocytes (from rabbit papillary muscles) and focussed on filament ultrastructure using either freeze-substitution or deep-etched replica methods to visualise connectin/titin filaments in fibers with and without actin and myosin filaments.
PubMed, 2008
Recent development of cluster of differentiation (CD) antibody arrays has enabled expression leve... more Recent development of cluster of differentiation (CD) antibody arrays has enabled expression levels of many leukocyte surface CD antigens to be monitored simultaneously. Such membrane-proteome surveys have provided a powerful means to detect changes in leukocyte activity in various human diseases, such as cancer and cardiovascular diseases. The challenge is to devise a computational method to infer differential leukocyte activity among multiple biological states based on antigen expression profiles. Standard DNA microarray analysis methods cannot accurately infer differential leukocyte activity because they often fail to take the cell-to-antigen relationships into account. Here we present a novel latent variable model (LVM) approach to tackle this problem. The idea is to model each cell type as a latent variable, and represent the class-to-cell and cell-to-antigen relationships as a LVM. Once the parameters of the LVM are learned from the data, differentially active leukocytes can be easily identified from the model. We describe the model formulation and assumptions which lead to an efficient expectation-maximization algorithm. Our LVM method was applied to re-analyze two cardiovascular disease datasets. We show that our results match existing biological knowledge better than other methods such as gene set enrichment analysis. Furthermore, we discuss how our approach can be extended to become a general framework for gene set analysis for DNA microarrays.
Biophysical Reviews, Jan 15, 2016
The Biophysical Reviews journal was created in the Spring of 2009 as an equal partnership between... more The Biophysical Reviews journal was created in the Spring of 2009 as an equal partnership between the International Union for Pure and Applied Biophysics (IUPAB) and the publisher, Springer (Heidelberg). It replaced Quarterly Reviews of Biophysics as the official journal of the IUPAB. Biophysics is sometimes described as the research that biophysicists do, but, more precisely, it can be defined as the science of examining biological phenomena using the concepts and techniques of physics. In particular, the new journal covers focussed reviews on topics in medical biophysics, biosystems biophysics, cell biophysics, molecular and macromolecular (proteins, DNA-RNA) biophysics, single-molecule biophysics, nanobiophysics, bioinformatics and computational biophysics. In practice, Biophysical Reviews publishes on biomembranes (ion channels, membrane receptors, membrane transport systems, membrane lipids), molecular motors (muscle contraction, cell motility), protein/lipid/nucleic acid structure and function. The 'A' in IUPAB stands for "Applied", and, so, biophysics is also concerned with the application of discoveries in biophysics to medicine and biology.
Excessive production of reactive oxygen species (ROS) is characteristic of numerous diseases, but... more Excessive production of reactive oxygen species (ROS) is characteristic of numerous diseases, but most studies in this area have not considered the impact of endogenous antioxidative defenses. Here, utilizing multi-omics, we demonstrate that in cardiomyocytes mitochondrial isocitrate dehydrogenase (IDH2) constitutes a major antioxidant defense. In both male and female mice and humans the paradoxical reduction in expression of IDH2 associated with heart failure is compensated for by an increase in the enzyme’s activity. We describe extensive mutual regulation of the antioxidant activities of IDH2 and NRF2 by a network involving 2-oxoglutarate and L2-hydroxyglutarate and mediated in part through unconventional hydroxymethylation of cytosine residues present in introns. Conditional targeting of ROS in a murine model of heart failure improves cardiac function. Together, these insights may explain why previous attempts to treat heart failure with antioxidants have been unsuccessful and o...
Biophysical Journal, Feb 1, 2018
Cells, 2019
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder. It is mainly cau... more Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder. It is mainly caused by mutations in genes encoding sarcomere proteins. Mutant forms of these highly abundant proteins likely stress the protein quality control (PQC) system of cardiomyocytes. The PQC system, together with a functional microtubule network, maintains proteostasis. We compared left ventricular (LV) tissue of nine donors (controls) with 38 sarcomere mutation-positive (HCMSMP) and 14 sarcomere mutation-negative (HCMSMN) patients to define HCM and mutation-specific changes in PQC. Mutations in HCMSMP result in poison polypeptides or reduced protein levels (haploinsufficiency, HI). The main findings were 1) several key PQC players were more abundant in HCM compared to controls, 2) after correction for sex and age, stabilizing heat shock protein (HSP)B1, and refolding, HSPD1 and HSPA2 were increased in HCMSMP compared to controls, 3) α-tubulin and acetylated α-tubulin levels were higher in HCM ...
Biophysical Reviews, 2017
In going into the new year of 2017, I thought it would be useful, in my role as Chief Editor, to ... more In going into the new year of 2017, I thought it would be useful, in my role as Chief Editor, to revisit the activity of Biophysical Reviews (BREV) in the previous year. In 2016 BREV published four issues with a progressive increase in the number and length of the reviews. The following is a resume of these contributions. Issue #1 contained eight articles dealing with a range of interesting topics. Navale and Paranjape (2016): This review described recent advances in glucose transporters that are needed for all living cells. These receptors are an essential component of all cells because they govern the intracellular supply of glucose for metabolism. Nakano and Sugimoto (2016): This review dealt with structural and catalytic effects of organic solvents on DNA and RNA oligonucleotides. This is important because the findings can be used for the development of oligonucleotide-based technologies. Inoue and Ishijima (2016): This manuscript described how carbon nanotubes can be used to monitor the ATPase activity of myosin molecules attached to carbon nanotubes, which can be directly heated without raising the temperature of heating the surrounding water, thus enabling evaluation of the direct effects of changes in activity of the myosin motor proteins as they interact with actin filaments. Nanobiophysics is becoming an increasingly "hot" topic and one for which Biophysical Reviews has appointed a specialist Editorial Board Member to help promote.
Biophysical Reviews, 2017
The basis for the 3Rs and Biophysics session is simple: We assume that no biophysicist would deli... more The basis for the 3Rs and Biophysics session is simple: We assume that no biophysicist would deliberately and unnecessarily kill an animal in the name of research. The 3Rs in the session title refer to Replacement, Reduction and Refinement of the use of animals in research. In different ways, the four speakers in this session address the 3Rs theme. While this session deals with all three aspects of the 3Rs, it places a strong emphasis on replacing animals in research. The first two speakers will focus on totally synthetic antibody-mimetic molecules (Affimers). These are antibodylike molecules but are much smaller (~100 amino acids, 10 kDa MW) (Tiede et al. 2017). Their small size provides huge advantages for researchers. Affimers comprise protein scaffolds that constrain regions of variable peptides to serve as molecular recognition motifs. Dr. Christian Tiede and his colleagues have generated a very large phage display library, up 2.3 × 10 10 , based on these Affimers. He will discuss the use of Affimers to bioscreen for chemicals, peptides, target proteins, and even complex cells and biofluids. He is currently screening highlyspecific Affimers directed against over 500 targets. Dr. Michelle Peckham discusses the use of Alexa-647labelled Affimers as antibody-mimetic probes (Kd 300 nm) for F-actin using both fixed and live cells. The red fluorescence means that troublesome autofluorescence is essentially avoided, and opens the way to using 'super-resolution' microscopy.
Biophysical Reviews, 2017
Biophysical Reviews, 2016
Biophysical Reviews, 2016
The Biophysical Reviews journal was created in the Spring of 2009 as an equal partnership between... more The Biophysical Reviews journal was created in the Spring of 2009 as an equal partnership between the International Union for Pure and Applied Biophysics (IUPAB) and the publisher, Springer (Heidelberg). It replaced Quarterly Reviews of Biophysics as the official journal of the IUPAB. Biophysics is sometimes described as the research that biophysicists do, but, more precisely, it can be defined as the science of examining biological phenomena using the concepts and techniques of physics. In particular, the new journal covers focussed reviews on topics in medical biophysics, biosystems biophysics, cell biophysics, molecular and macromolecular (proteins, DNA-RNA) biophysics, single-molecule biophysics, nanobiophysics, bioinformatics and computational biophysics. In practice, Biophysical Reviews publishes on biomembranes (ion channels, membrane receptors, membrane transport systems, membrane lipids), molecular motors (muscle contraction, cell motility), protein/lipid/nucleic acid structure and function. The 'A' in IUPAB stands for "Applied", and, so, biophysics is also concerned with the application of discoveries in biophysics to medicine and biology.
Journal of Molecular and Cellular Cardiology, 1981
Biophysical Journal, 2007
Biophysical Journal, May 1, 2004
Fluorescence polarization measurements were used to study changes in the orientation and order of... more Fluorescence polarization measurements were used to study changes in the orientation and order of different sites on actin monomers within muscle thin filaments during weak or strong binding states with myosin subfragment-1. Ghost muscle fibers were supplemented with actin monomers specifically labeled with different fluorescent probes at Cys-10, Gln-41, Lys-61, Lys-373, Cys-374, and the nucleotide binding site. We also used fluorescent phalloidin as a probe near the filament axis. Changes in the orientation of the fluorophores depend not only on the state of acto-myosin binding but also on the location of the fluorescent probes. We observed changes in polarization (i.e., orientation) for those fluorophores attached at the sites directly involved in myosin binding (and located at high radii from the filament axis) that were contrary to the fluorophores located at the sites close to the axis of thin filament. These altered probe orientations suggest that myosin binding alters the conformation of F-actin. Strong binding by myosin heads produces changes in probe orientation that are opposite to those observed during weak binding.
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Papers by Cristobal dos Remedios