scholarly journals Human Plasma and Recombinant Hemopexins: Heme Binding Revisited

2020 ◽  
Author(s):  
Elena Karnaukhova ◽  
Catherine Owczarek ◽  
Peter Schmidt ◽  
Dominik J. Schaer ◽  
Paul W. Buehler
Keyword(s):  
Protein S ◽  
Soret Band ◽  
Cell System ◽  
Heme Binding ◽  
Systematic Analysis ◽  
Molar Ratios ◽  
Recombinant Production ◽  
Wide Range ◽  
Titration Data ◽  
First Time

Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin. During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), SEC-HPLC and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX-heme interactions to approximate physiological conditions (from extremely low to more than 2-fold heme excess). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggests more than one binding site in both plasma and rhHPX. Further, our study provides a useful analytical platform for detailed characterization of HPX-heme interactions and potentially, novel HPX fusion constructs.

scholarly journals Human Plasma and Recombinant Hemopexins: Heme Binding Revisited

2021 ◽  
Vol 22 (3) ◽  
pp. 1199
Author(s):  
Elena Karnaukhova ◽  
Catherine Owczarek ◽  
Peter Schmidt ◽  
Dominik J. Schaer ◽  
Paul W. Buehler
Keyword(s):  
Protein S ◽  
Soret Band ◽  
Cell System ◽  
Size Exclusion ◽  
Heme Binding ◽  
Systematic Analysis ◽  
Molar Ratios ◽  
Recombinant Production ◽  
Wide Range ◽  
Exclusion Chromatography

Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin (the term “heme” is used in this article to denote both the ferrous and ferric forms). During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), size-exclusion chromatography (SEC)-HPLC, and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX–heme interactions to approximate physiological conditions (from extremely low to more than two-fold heme molar excess over the protein). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggest more than one binding site in both plasma and rhHPX. Furthermore, our study provides a useful analytical platform for the detailed characterization of HPX–heme interactions and potentially novel HPX fusion constructs.

Safety assessment of biological raw materials in the system of medicines quality assurance

2020 ◽  
pp. 63-72
Author(s):  
Yu. Olefir ◽  
E. Sakanyan ◽  
I. Osipova ◽  
V. Dobrynin ◽  
M. Smirnova ◽  
...  
Keyword(s):  
Raw Materials ◽  
State Level ◽  
The State ◽  
Spongiform Encephalopathy ◽  
Safety Standards ◽  
Wide Range ◽  
The Russian Federation ◽  
Key Aspects ◽  
First Time ◽  
Medicines Quality

The entry of a wide range of biotechnological products into the pharmaceutical market calls for rein-forcement of the quality, efficacy and safety standards at the state level. The following general monographs have been elaborated for the first time to be included into the State Pharmacopoeia of the Russian Federation, XIV edition: "Viral safety" and "Reduction of the risk of transmitting animal spongiform encephalopathy via medicinal products". These general monographs were elaborated taking into account the requirements of foreign pharmacopoeias and the WHO recommendations. The present paper summarises the key aspects of the monographs.

Innovation in Byzantine Medicine

2020 ◽  
Author(s):  
Petros Bouras-Vallianatos
Keyword(s):  
Human Physiology ◽  
Medical Literature ◽  
Cultural Exchange ◽  
Significant Degree ◽  
Medieval Medicine ◽  
Medieval Latin ◽  
Main Thesis ◽  
Wide Range ◽  
Comprehensive Examination ◽  
First Time

Byzantine medicine is still a little-known and misrepresented field not only in the wider arena of debates on medieval medicine but also among Byzantinists. Byzantine medical literature is often viewed as ‘stagnant’ and mainly preserving ancient ideas; and our knowledge of it continues to be based to a great extent on the comments of earlier authorities, which are often repeated uncritically. This book presents the first comprehensive examination of the medical corpus of, arguably, the most important late Byzantine physician John Zacharias Aktouarios (c.1275–c.1330). The main thesis is that John’s medical works show an astonishing degree of openness to knowledge from outside Byzantium combined with a significant degree of originality, in particular, in the fields of uroscopy, pharmacology, and human physiology. The analysis of John’s edited (On Urines and On Psychic Pneuma) and unedited (Medical Epitome) works is supported for the first time by the consultation of a large number of manuscripts. The study is also informed by evidence from a wide range of medical sources, including previously unpublished ones, and texts from other genres, such as epistolography and merchants’ accounts. The contextualization of John’s works sheds new light on the development of Byzantine medical thought and practice, and enhances our understanding of the late Byzantine social and intellectual landscape. Finally, John’s medical observations are also examined in the light of examples from the medieval Latin and Islamic worlds, placing his medical theories in the wider Mediterranean milieu and highlighting the cultural exchange between Byzantium and its neighbours.

Rebels, Believers, Survivors

2020 ◽  
Author(s):  
Noel Malcolm
Keyword(s):  
Catholic Church ◽  
Religious Conversion ◽  
Late Nineteenth Century ◽  
Napoleonic Wars ◽  
Conversion To Islam ◽  
Wide Range ◽  
History Of ◽  
External Powers ◽  
First Time ◽  
Modern Myth

This book of essays covers a wide range of topics in the history of Albania and Kosovo. Many of the essays illuminate connections between the Albanian lands and external powers and interests, whether political, military, diplomatic or religious. Such topics include the Habsburg invasion of Kosovo in 1689, the manoeuvrings of Britain and France towards the Albanian lands during the Napoleonic Wars, the British interest in those lands in the late nineteenth century, and the Balkan War of 1912. On the religious side, essays examine ‘crypto-Christianity’ in Kosovo during the Ottoman period, the stories of conversion to Islam revealed by Inquisition records, the first theological treatise written in Albanian (1685), and the work of the ‘Apostolic Delegate’ who reformed the Catholic Church in early twentieth-century Albania. Some essays bring to life ordinary individuals hitherto unknown to history: women hauled before the Inquisition, for example, or the author of the first Albanian autobiography. The longest essay, on Ali Pasha, tells for the first time the full story of the role he played in the international politics of the Napoleonic Wars. Some of these studies have been printed before (several in hard-to-find publications, and one only in Albanian), but the greater part of this book appears here for the first time. This is not only a contribution to Albanian and Balkan history it also engages with many broader issues, including religious conversion, methods of enslavement within the Ottoman Empire, and the nature of modern myth-making about national identity.

Recycling and Reuse in the Roman Economy

2020 ◽  
Keyword(s):  
Building Materials ◽  
Computational Modelling ◽  
Late Antique ◽  
Roman Economy ◽  
Wide Range ◽  
The Status ◽  
Recent Developments ◽  
Methodological Approaches ◽  
First Time ◽  
Site Types

The recycling and reuse of materials and objects were extensive in the past, but have rarely been embedded into models of the economy; even more rarely has any attempt been made to assess the scale of these practices. Recent developments, including the use of large datasets, computational modelling, and high-resolution analytical chemistry, are increasingly offering the means to reconstruct recycling and reuse, and even to approach the thorny matter of quantification. Growing scholarly interest in the topic has also led to an increasing recognition of these practices from those employing more traditional methodological approaches, which are sometimes coupled with innovative archaeological theory. Thanks to these efforts, it has been possible for the first time in this volume to draw together archaeological case studies on the recycling and reuse of a wide range of materials, from papyri and textiles, to amphorae, metals and glass, building materials and statuary. Recycling and reuse occur at a range of site types, and often in contexts which cross-cut material categories, or move from one object category to another. The volume focuses principally on the Roman Imperial and late antique world, over a broad geographical span ranging from Britain to North Africa and the East Mediterranean. Last, but not least, the volume is unique in focusing upon these activities as a part of the status quo, and not just as a response to crisis.

scholarly journals A Virtual Telescope for the Open University Science Foundation Course

1998 ◽  
Vol 162 ◽  
pp. 100-105
Author(s):  
Andrew J. Norton ◽  
Mark H. Jones
Keyword(s):  
Social Science ◽  
Open University ◽  
Distance Teaching ◽  
The Arts ◽  
Wide Range ◽  
University Science ◽  
First Time ◽  
Degree Level ◽  
Selection Of

The Open University is the UK's foremost distance teaching university. For over twenty five years we have been presenting courses to students spanning a wide range of degree level and vocational subjects. Since we have no pre-requisites for entry, a major component of our course profile is a selection of foundation courses comprising one each in the Arts, Social Science, Mathematics, Technology and Science faculties. The Science Faculty's foundation course is currently undergoing a substantial revision. The new course, entitled “S103: Discovering Science”, will be presented to students for the first time in 1998.

scholarly journals Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 481
Author(s):  
Gemma G. Martínez-García ◽  
Raúl F. Pérez ◽  
Álvaro F. Fernández ◽  
Sylvere Durand ◽  
Guido Kroemer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Mammalian Cells ◽  
Tissue Homeostasis ◽  
In Vivo Studies ◽  
Protective Mechanism ◽  
Cardiac Damage ◽  
Wide Range ◽  
First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

scholarly journals Recent Advances in Unmanned Aerial Vehicle Forest Remote Sensing—A Systematic Review. Part I: A General Framework

Forests ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 327 ◽  
Author(s):  
Riccardo Dainelli ◽  
Piero Toscano ◽  
Salvatore Filippo Di Gennaro ◽  
Alessandro Matese
Keyword(s):  
Remote Sensing ◽  
Unmanned Aerial Vehicle ◽  
Relevant Information ◽  
Forest Monitoring ◽  
Machine Learning Techniques ◽  
Planted Forests ◽  
Systematic Analysis ◽  
Aerial Photogrammetry ◽  
Wide Range ◽  
Aerial Vehicle

Natural, semi-natural, and planted forests are a key asset worldwide, providing a broad range of positive externalities. For sustainable forest planning and management, remote sensing (RS) platforms are rapidly going mainstream. In a framework where scientific production is growing exponentially, a systematic analysis of unmanned aerial vehicle (UAV)-based forestry research papers is of paramount importance to understand trends, overlaps and gaps. The present review is organized into two parts (Part I and Part II). Part II inspects specific technical issues regarding the application of UAV-RS in forestry, together with the pros and cons of different UAV solutions and activities where additional effort is needed, such as the technology transfer. Part I systematically analyzes and discusses general aspects of applying UAV in natural, semi-natural and artificial forestry ecosystems in the recent peer-reviewed literature (2018–mid-2020). The specific goals are threefold: (i) create a carefully selected bibliographic dataset that other researchers can draw on for their scientific works; (ii) analyze general and recent trends in RS forest monitoring (iii) reveal gaps in the general research framework where an additional activity is needed. Through double-step filtering of research items found in the Web of Science search engine, the study gathers and analyzes a comprehensive dataset (226 articles). Papers have been categorized into six main topics, and the relevant information has been subsequently extracted. The strong points emerging from this study concern the wide range of topics in the forestry sector and in particular the retrieval of tree inventory parameters often through Digital Aerial Photogrammetry (DAP), RGB sensors, and machine learning techniques. Nevertheless, challenges still exist regarding the promotion of UAV-RS in specific parts of the world, mostly in the tropical and equatorial forests. Much additional research is required for the full exploitation of hyperspectral sensors and for planning long-term monitoring.

scholarly journals Fructose Enhanced Reduction of Bacterial Growth on Nanorough Surfaces

2013 ◽  
Vol 1498 ◽  
pp. 73-78 ◽  
Author(s):  
N. Gozde Durmus ◽  
Erik N. Taylor ◽  
Kim M. Kummer ◽  
Thomas J. Webster
Keyword(s):  
Bacterial Growth ◽  
Biofilm Formation ◽  
Antibacterial Agents ◽  
Bacteria Growth ◽  
Planktonic Bacteria ◽  
Combined Use ◽  
Wide Range ◽  
Metabolic Stimulation ◽  
Antibacterial Surfaces ◽  
First Time

ABSTRACTBiofilms are a major source of medical device-associated infections, due to their persistent growth and antibiotic resistance. Recent studies have shown that engineering surface nanoroughness has great potential to create antibacterial surfaces. In addition, stimulation of bacterial metabolism increases the efficacy of antibacterial agents to eradicate biofilms. In this study, we combined the antibacterial effects of nanorough topographies with metabolic stimulation (i.e., fructose metabolites) to further decrease bacterial growth on polyvinyl chloride (PVC) surfaces, without using antibiotics. We showed for the first time that the presence of fructose on nanorough PVC surfaces decreased planktonic bacteria growth and biofilm formation after 24 hours. Most importantly, a 60% decrease was observed on nanorough PVC surfaces soaked in a 10 mM fructose solution compared to conventional PVC surfaces. In this manner, this study demonstrated that bacteria growth can be significantly decreased through the combined use of fructose and nanorough surfaces and thus should be further studied for a wide range of antibacterial applications.

ECCENTRIC, GIFTED, AND BLACK: THELONIOUS MONK REVEALED

2010 ◽  
Vol 7 (2) ◽  
pp. 381-402
Author(s):  
Ingrid Monson ◽  
John Gennari ◽  
Travis A. Jackson
Keyword(s):  
Primary Research ◽  
Thelonious Monk ◽  
Wide Range ◽  
American Composer ◽  
Personal Archives ◽  
To Come ◽  
The Right ◽  
First Time

Do not miss Robin D. G. Kelley's Thelonious Monk: The Life and Times of an American Original, for it will stand as the definitive biography of the great American composer and pianist for many years to come. What distinguishes Kelley's treatment of Monk's complicated and enigmatic life is the sheer depth and breadth of primary research, including, for the first time, the active cooperation and involvement of Thelonious Monk's family. In his acknowledgments, Kelley describes a long process of convincing Thelonious Monk, III to grant permission culminating in a six-hour meeting in which his knowledge, credentials, and commitment were thoroughly tested and challenged. Once he had secured “Toot's” blessings, as well as that of his wife Gale and brother-in-law Peter Grain, Kelley was introduced to Nellie Monk, Thelonious Monk's wife, and a wide range of family and friends who shared their memories and personal archives of photos, recordings, and papers. This is not an authorized biography, however, since Thelonious Monk, Jr. never demanded the right to see drafts or dictate the content. Rather Kelley was admonished to “dig deep and tell the truth.”

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