Crystallization of the human tetraspanin protein CD9

The tetraspanin family of proteins with four membrane-spanning proteins function in a wide range of physiological processes in higher organisms, including cell migration and proliferation, cell fusion, fertilization and virus infection. Although the recently reported structure of CD81 unveiled the basic architecture of this family for the first time, further structural and functional studies are required in order to understand the mechanistic details of the complicated functions of the tetraspanin-family proteins. In this study, attempts were made to crystallize human CD9, a representative member of the tetraspanin family, and it was demonstrated that the truncation of a variable region in the second long extracellular loop significantly improved crystal growth.

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

10.33920/med-06-2002-05 ◽

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.

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Innovation in Byzantine Medicine

10.1093/oso/9780198850687.001.0001 ◽

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.

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Rebels, Believers, Survivors

10.1093/oso/9780198857297.001.0001 ◽

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.

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Recycling and Reuse in the Roman Economy

10.1093/oso/9780198860846.001.0001 ◽

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.

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A Virtual Telescope for the Open University Science Foundation Course

International Astronomical Union Colloquium ◽

10.1017/s0252921100114885 ◽

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.

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Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽

10.3390/metabo11080481 ◽

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.

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Membrane Lipid Composition of the Moderately Thermophilic Ammonia-Oxidizing Archaeon “Candidatus Nitrosotenuis uzonensis” at Different Growth Temperatures

Applied and Environmental Microbiology ◽

10.1128/aem.01332-19 ◽

2019 ◽

Vol 85 (20) ◽

Cited By ~ 4

Author(s):

Nicole J. Bale ◽

Marton Palatinszky ◽

W. Irene C. Rijpstra ◽

Craig W. Herbold ◽

Michael Wagner ◽

...

Keyword(s):

Lipid Composition ◽

Strong Influence ◽

Thermal Spring ◽

Membrane Lipid ◽

Effect Of Temperature ◽

Environmental Niche ◽

Membrane Lipid Composition ◽

Moderately Thermophilic ◽

Wide Range ◽

Membrane Spanning

ABSTRACT “Candidatus Nitrosotenuis uzonensis” is the only cultured moderately thermophilic member of the thaumarchaeotal order Nitrosopumilales (NP) that contains many mesophilic marine strains. We examined its membrane lipid composition at different growth temperatures (37°C, 46°C, and 50°C). Its lipids were all membrane-spanning glycerol dialkyl glycerol tetraethers (GDGTs), with 0 to 4 cyclopentane moieties. Crenarchaeol (cren), the characteristic thaumarchaeotal GDGT, and its isomer (crenʹ) were present in high abundance (30 to 70%). The GDGT polar headgroups were mono-, di-, and trihexoses and hexose/phosphohexose. The ratio of glycolipid to phospholipid GDGTs was highest in the cultures grown at 50°C. With increasing growth temperatures, the relative contributions of cren and crenʹ increased, while those of GDGT-0 to GDGT-4 (including isomers) decreased. TEX86 (tetraether index of tetraethers consisting of 86 carbons)-derived temperatures were much lower than the actual growth temperatures, further demonstrating that TEX86 does not accurately reflect the membrane lipid adaptation of thermophilic Thaumarchaeota. As the temperature increased, specific GDGTs changed relative to their isomers, possibly representing temperature adaption-induced changes in cyclopentane ring stereochemistry. Comparison of a wide range of thaumarchaeotal core lipid compositions revealed that the “Ca. Nitrosotenuis uzonensis” cultures clustered separately from other members of the NP order and the Nitrososphaerales (NS) order. While phylogeny generally seems to have a strong influence on GDGT distribution, our analysis of “Ca. Nitrosotenuis uzonensis” demonstrates that its terrestrial, higher-temperature niche has led to a lipid composition that clearly differentiates it from other NP members and that this difference is mostly driven by its high crenʹ content. IMPORTANCE For Thaumarchaeota, the ratio of their glycerol dialkyl glycerol tetraether (GDGT) lipids depends on growth temperature, a premise that forms the basis of the widely applied TEX86 paleotemperature proxy. A thorough understanding of which GDGTs are produced by which Thaumarchaeota and what the effect of temperature is on their GDGT composition is essential for constraining the TEX86 proxy. “Ca. Nitrosotenuis uzonensis” is a moderately thermophilic thaumarchaeote enriched from a thermal spring, setting it apart in its environmental niche from the other marine mesophilic members of its order. Indeed, we found that the GDGT composition of “Ca. Nitrosotenuis uzonensis” cultures was distinct from those of other members of its order and was more similar to those of other thermophilic, terrestrial Thaumarchaeota. This suggests that while phylogeny has a strong influence on GDGT distribution, the environmental niche that a thaumarchaeote inhabits also shapes its GDGT composition.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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Rtn1p Is Involved in Structuring the Cortical Endoplasmic Reticulum

Molecular Biology of the Cell ◽

10.1091/mbc.e06-01-0080 ◽

2006 ◽

Vol 17 (7) ◽

pp. 3009-3020 ◽

Cited By ~ 90

Author(s):

Johan-Owen De Craene ◽

Jeff Coleman ◽

Paula Estrada de Martin ◽

Marc Pypaert ◽

Scott Anderson ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Nuclear Envelope ◽

Fluorescent Protein ◽

Cell Cortex ◽

Proteomic Screen ◽

Wide Range ◽

Membrane Spanning ◽

Green Fluorescent ◽

Hydrophilic Loop ◽

Yeast Mutants

The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous structure. We identified rtn1Δ in a systematic screen for yeast mutants with altered ER morphology. The ER in rtn1Δ cells is predominantly cisternal rather than reticular, yet the net surface area of ER is not significantly changed. Rtn1-green fluorescent protein (GFP) associates with the reticular ER at the cell cortex and with the tubules that connect the cortical ER to the nuclear envelope, but not with the nuclear envelope itself. Rtn1p overexpression also results in an altered ER structure. Rtn proteins are found on the ER in a wide range of eukaryotes and are defined by two membrane-spanning domains flanking a conserved hydrophilic loop. Our results suggest that Rtn proteins may direct the formation of reticulated ER. We independently identified Rtn1p in a proteomic screen for proteins associated with the exocyst vesicle tethering complex. The conserved hydophilic loop of Rtn1p binds to the exocyst subunit Sec6p. Overexpression of this loop results in a modest accumulation of secretory vesicles, suggesting impaired exocyst function. The interaction of Rtn1p with the exocyst at the bud tip may trigger the formation of a cortical ER network in yeast buds.

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Fructose Enhanced Reduction of Bacterial Growth on Nanorough Surfaces

MRS Proceedings ◽

10.1557/opl.2013.35 ◽

2013 ◽

Vol 1498 ◽

pp. 73-78 ◽

Cited By ~ 2

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.

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