scholarly journals Biogenesis of cytochrome b6 in photosynthetic membranes

2009 ◽  
Vol 185 (7) ◽  
pp. 1195-1207 ◽  
Author(s):  
Denis Saint-Marcoux ◽  
Francis-André Wollman ◽  
Catherine de Vitry
Keyword(s):  
Preliminary Evidence ◽  
Thylakoid Membranes ◽  
Major Protein ◽  
Heme Binding ◽  
Specific Mechanism ◽  
Cytochrome B6 ◽  
Assembly Pathway ◽  
Bona Fide ◽  
Protein Components ◽  
The One

In chloroplasts, binding of a c′-heme to cytochrome b6 on the stromal side of the thylakoid membranes requires a specific mechanism distinct from the one at work for c-heme binding to cytochromes f and c6 on the lumenal side of membranes. Here, we show that the major protein components of this pathway, the CCBs, are bona fide transmembrane proteins. We demonstrate their association in a series of hetero-oligomeric complexes, some of which interact transiently with cytochrome b6 in the process of heme delivery to the apoprotein. In addition, we provide preliminary evidence for functional assembly of cytochrome b6f complexes even in the absence of c′-heme binding to cytochrome b6. Finally, we present a sequential model for apo- to holo-cytochrome b6 maturation integrated within the assembly pathway of b6f complexes in the thylakoid membranes.

Avenues to Precision Oncology

2020 ◽  
pp. 36-45
Author(s):  
Alexander Meisel
Keyword(s):  
Precision Medicine ◽  
Trial Design ◽  
Ad Hoc ◽  
Molecular Targets ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Precision Oncology ◽  
Companion Diagnostics ◽  
Bona Fide ◽  
The One

Until recently, the clinical management of cancer heavily relied on anatomical and histopathological criteria, with ad hoc guidelines directing the therapeutic choices in specific indications. In the last years, the development and therapeutic implementation of novel anticancer therapies significantly improved the clinical outcome of cancer patients. Nonetheless, such cutting-edge approaches revealed the limitation of the one-size-fits-all paradigm. The newly discovered molecular targets can be exploited either as bona fide targets for subsequent drug development, or as tools to precision medicine, in the form of prognostic and/or predictive biomarkers. This article provides an overview of some of the most recent advances in precision medicine in oncology, with a focus on novel tissue-agnostic anticancer therapies. The definition and implementation of biomarkers and companion diagnostics in clinical trials and clinical practice are also discussed, as well as the changing landscape in clinical trial design.

Characterization of excretory–secretory products from protoscoleces of Echinococcus granulosus and evaluation of their potential for immunodiagnosis of human cystic echinococcosis

Parasitology ◽  
2004 ◽  
Vol 129 (3) ◽  
pp. 371-378 ◽  
Author(s):  
D. CARMENA ◽  
J. MARTÍNEZ ◽  
A. BENITO ◽  
J. A. GUISANTES
Keyword(s):  
Echinococcus Granulosus ◽  
Cystic Echinococcosis ◽  
Secretory Protein ◽  
Major Protein ◽  
Healthy Donors ◽  
Secretory Products ◽  
Protein Components ◽  
Human Cystic Echinococcosis

This study describes, for the first time, the characterization of excretory–secretory antigens (ES-Ag) from Echinococcus granulosus protoscoleces, evaluating their usefulness in the immunodiagnosis of human cystic echinococcosis. ES-Ag were obtained from the first 50 h maintenance of protoscoleces in vitro. This preparation contained over 20 major protein components which could be distinguished by 1-dimensional SDS–PAGE with apparent masses between 9 and 300 kDa. The culture of of protoscoleces from liver produced a greater variety of excretory–secretory protein components than those from lung. Determination of enzymatic activities of secreted proteins revealed the presence of phosphatases, lipases and glucosidases, but no proteases. These findings were compared to those obtained from somatic extracts of protoscoleces and hydatid cyst fluid products. Immunochemical characterization was performed by immunoblotting with sera from individuals infected by cystic echinococcosis (n=15), non-hydatidic parasitoses (n=19), various liver diseases (n=24), lung neoplasia (n=16), and healthy donors (n=18). Antigens with apparent masses of 89, 74, 47/50, 32, and 20 kDa showed specificity for immunodiagnosis of human hydatidosis. The 89 and 74 kDa components corresponded to antigens not yet described in E. granulosus, whereas proteins of 41–43 kDa and 91–95 kDa were recognized by the majority of the non-hydatid sera studied.

Stage-specific patterns of collagen gene expression during development of Caenorhabditis elegans

1985 ◽  
Vol 5 (2) ◽  
pp. 363-372
Author(s):  
G N Cox ◽  
D Hirsh
Keyword(s):  
Caenorhabditis Elegans ◽  
Protein Composition ◽  
Large Family ◽  
Major Protein ◽  
Mrna Levels ◽  
Mrna Accumulation ◽  
C Elegans ◽  
Collagen Protein ◽  
Protein Components ◽  
Collagen Genes

Collagens are the major protein components of the Caenorhabditis elegans cuticle and are encoded by a large family of 40 to 150 closely related but nonidentical genes. We have determined temporal patterns of mRNA accumulation for a large number of collagen genes by screening recombinant phages and plasmids containing cloned collagen genes under high stringency conditions with 32P-labeled cDNA preparations specific for eggs or three postembryonic molts. We find that collagen mRNA levels are regulated both temporally and quantitatively during C. elegans development. Most genes studied exhibit one of four patterns of mRNA accumulation which correlate with changes in cuticle morphology and collagen protein composition during development. Our results suggest that, in general, there is a progressive activation of new collagen genes during normal development.

Is Cognitive Psychopathology Plausible? Illustrations from Memory Research

1996 ◽  
Vol 41 (7) ◽  
pp. S5-S13 ◽  
Author(s):  
Jean-Marie Danion ◽  
Herbert Weingartner ◽  
Leonard Singer
Keyword(s):  
Cognitive Remediation ◽  
Preliminary Evidence ◽  
Limiting Factors ◽  
Specific Rate ◽  
Memory Impairments ◽  
Central Processing ◽  
Elementary Computation ◽  
The One ◽  
Functional Mechanisms ◽  
Rate Limiting

Objective: To examine the strengths and weaknesses of cognitive psychopathology through the specific examples of the memory impairments associated with the administration of benzodiazepines, with schizophrenia, and with depression. Method: These examples are analyzed with reference to a model of memory based on the principle of division between specialized and central processing structures. A basic contention is that it is useful to consider 2 broad classes of processes—automatic, associative, or sensory/perceptual processes on the one hand and intentional, strategic, or reflective processes on the other hand—as being separate. Results: The functional mechanisms of the memory impairments associated with these conditions are beginning to be identified, and there is preliminary evidence that a deficit in an elementary computation may have dramatic consequences on highest cognitive functions. There is also evidence that certain memory impairments are linked to specific dysfunctional outcomes in everyday life. By showing that specific rate-limiting factors of cognitive performance can be identified and are amenable to cognitive interventions, existing data open the door for theoretically and empirically based cognitive remediation of mental disorders. Conclusion: The bulk of available evidence (albeit limited) makes the enterprise of cognitive psychopathology quite plausible and convincing.

scholarly journals Identification and Analysis of Bacterial Protein Secretion Inhibitors Utilizing a SecA-LacZ Reporter Fusion System

2000 ◽  
Vol 44 (6) ◽  
pp. 1418-1427 ◽  
Author(s):  
L. E. Alksne ◽  
P. Burgio ◽  
W. Hu ◽  
B. Feld ◽  
M. P. Singh ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Antimicrobial Agents ◽  
Membrane Integrity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reporter Construct ◽  
Central Protein ◽  
Bona Fide ◽  
Membrane Bound ◽  
Protein Components

ABSTRACT Protein secretion is an essential process for bacterial growth, yet there are few if any antimicrobial agents which inhibit secretion. An in vivo, high-throughput screen to detect secretion inhibitors was developed based on the translational autoregulation of one of the central protein components, SecA. The assay makes use of a SecA-LacZ fusion reporter construct in Escherichia coli which is induced when secretion is perturbed. Several compounds, including two natural product extracts, which had the ability to induce the reporter fusion were identified and the MICs of these compounds forStaphylococcus aureus strain MN8 were found to be ≤128 μg/ml. Enzyme-linked immunosorbent assay, Western blotting, and immunoprecipitation techniques were used to analyze the affects of these compounds on protein secretion. Six representative compounds presented here appear to be bona fide secretion inhibitors but were found to have deleterious effects on membranes. It was concluded that, while the method described here for identifying inhibitors of secretion is valid, screens such as this, which are directed against the membrane-bound portion of a pathway, may preferentially identify compounds which affect membrane integrity.

scholarly journals Venomics and Cellular Toxicity of Thai Pit Vipers (Trimeresurus macrops and T. hageni)

Toxins ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 54 ◽  
Author(s):  
Supeecha Kumkate ◽  
Lawan Chanhome ◽  
Tipparat Thiangtrongjit ◽  
Jureeporn Noiphrom ◽  
Panithi Laoungboa ◽  
...  
Keyword(s):  
Snake Venom ◽  
Protein Composition ◽  
Treatment Method ◽  
Cross Reactivity ◽  
Major Protein ◽  
Dependent Manner ◽  
Crude Venom ◽  
Monocytic Cells ◽  
Protein Components ◽  
Species Specific

The two venomous pit vipers, Trimeresurus macrops and T. hageni, are distributed throughout Thailand, although their abundance varies among different areas. No species-specific antivenom is available for their bite victims, and the only recorded treatment method is a horse antivenom raised against T. albolabris crude venom. To facilitate assessment of the cross-reactivity of heterologous antivenoms, protein profiles of T. macrops and T. hageni venoms were explored using mass-spectrometry-based proteomics. The results show that 185 and 216 proteins were identified from T. macrops and T. hageni venoms, respectively. Two major protein components in T. macrops and T. hageni venoms were snake venom serine protease and metalloproteinase. The toxicity of the venoms on human monocytes and skin fibroblasts was analyzed, and both showed a greater cytotoxic effect on fibroblasts than monocytic cells, with toxicity occurring in a dose-dependent rather than a time-dependent manner. Exploring the protein composition of snake venom leads to a better understanding of the envenoming of prey. Moreover, knowledge of pit viper venomics facilitates the selection of the optimum heterologous antivenoms for treating bite victims.

scholarly journals Mechanics and thermodynamics of a new minimal model of the atmosphere

2020 ◽  
Vol 135 (10) ◽  
Author(s):  
Gabriele Vissio ◽  
Valerio Lucarini
Keyword(s):  
Numerical Models ◽  
Preliminary Evidence ◽  
Chaotic Motions ◽  
One Dimensional ◽  
Fundamental Properties ◽  
Multiscale Dynamics ◽  
Energy Cycle ◽  
The One ◽  
Lorenz 96 ◽  
Model Features

AbstractThe understanding of the fundamental properties of the climate system has long benefitted from the use of simple numerical models able to parsimoniously represent the essential ingredients of its processes. Here, we introduce a new model for the atmosphere that is constructed by supplementing the now-classic Lorenz ’96 one-dimensional lattice model with temperature-like variables. The model features an energy cycle that allows for energy to be converted between the kinetic form and the potential form and for introducing a notion of efficiency. The model’s evolution is controlled by two contributions—a quasi-symplectic and a gradient one, which resemble (yet not conforming to) a metriplectic structure. After investigating the linear stability of the symmetric fixed point, we perform a systematic parametric investigation that allows us to define regions in the parameters space where at steady-state stationary, quasi-periodic, and chaotic motions are realised, and study how the terms responsible for defining the energy budget of the system depend on the external forcing injecting energy in the kinetic and in the potential energy reservoirs. Finally, we find preliminary evidence that the model features extensive chaos. We also introduce a more complex version of the model that is able to accommodate for multiscale dynamics and that features an energy cycle that more closely mimics the one of the Earth’s atmosphere.

scholarly journals The 72/74-kDa polypeptides of the 70–110S large heterogeneous nuclear ribonucleoprotein complex (LH-nRNP) represent a discrete subset of the hnRNP M protein family

2000 ◽  
Vol 350 (2) ◽  
pp. 495-503 ◽  
Author(s):  
Panayiota KAFASLA ◽  
Meropi PATRINOU-GEORGOULA ◽  
Apostolia GUIALIS
Keyword(s):  
Matrix Protein ◽  
Polyclonal Antibodies ◽  
Protein Family ◽  
M Protein ◽  
Major Protein ◽  
Discrete Subset ◽  
Two Dimensional Gel Electrophoresis ◽  
Nuclear Extracts ◽  
Protein Components ◽  
Nuclear Ribonucleoprotein

Pre-mRNA processing in eukaryotes is thought to take place on a multitude of nuclear ribonucleoprotein (RNP) complexes, the most abundant of them being the heterogeneous nuclear (hn) RNP complexes. The identification in mammalian nuclear extracts of a novel, less-abundant 70–110S heterogeneous RNP, named large heterogeneous nuclear RNP (LH-nRNP), has previously been reported by Aidinis, Sekeris and Guialis (1995) Nucleic Acids Res. 23, 2742–2753. The structural composition of the LH-nRNP complex has been determined following the production of polyclonal antibodies against the major protein constituents of the complex, the pair of the 72/74-kDa polypeptides. In the present study evidence is shown to prove that the 72/74-kDa proteins are members of the hnRNP M protein family, hereafter referred to as 72/74(M) polypeptides. The extensive application of two-dimensional gel electrophoresis, combined with specific immunoprecipitation and immunoblotting assays, has allowed the assignment of the 72/74(M) proteins to a subset of the hnRNP M family, characteristic of the presence of the LH-nRNP complex and distinct from the hnRNP-associated M1–M4 components. Moreover, the immunoselection of the LH-nRNP complex from [32P]orthophosphate-labelled HeLa cells, with the parallel application of UV irradiation, has permitted the identification of the 72/74(M) polypeptides as the sole protein constituents of the complex in direct contact with the RNA. It is proposed that LH-nRNP constitutes a discrete subset of hnRNP complexes, having a possible role in establishing specific interactions between hnRNP and nuclear-matrix protein components.

The Positive and Negative Suicide Ideation Inventory: Development and Validation

1998 ◽  
Vol 82 (3) ◽  
pp. 783-793 ◽  
Author(s):  
Augustine Osman ◽  
Peter M. Gutierrez ◽  
Beverly A. Kopper ◽  
Francisco X. Barrios ◽  
Christine E. Chiros
Keyword(s):  
Factor Analysis ◽  
Suicidal Behavior ◽  
Suicide Ideation ◽  
Factor Model ◽  
Preliminary Evidence ◽  
Self Report ◽  
Negative Thoughts ◽  
Principal Axis Factor Analysis ◽  
The One ◽  
Report Measure

We conducted two studies to develop and validate a brief self-report measure for assessing the frequency of positive and negative thoughts related to suicidal behavior Items on this new measure, the Positive and Negative Suicide Ideation inventory, were generated by undergraduates. In Study 1, we administered a 20-item version of the inventory to 150 male and 300 female undergraduates and conducted an exploratory principal axis factor analysis with varimax rotation. Two factors, Positive Ideation and Negative Ideation, were retained. In Study 2, we conducted a confirmatory factor analysis to validate the fit of the one-factor and the oblique two-factor models to data from another sample of 84 men and 202 women. The oblique two-factor model provided an excellent fit to the sample data. We also examined preliminary evidence of concurrent and predictive validity. Over-all, these findings suggested that the inventory is a well-developed self-report measure for assessing the frequency of positive and negative thoughts related to suicidal behavior.

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