Elucidating the role of carbohydrate determinants in regulating hemostasis: insights and opportunities

Recent improvement in modern analytical technologies has stimulated an explosive growth in the study of glycobiology. In turn, this has lead to a richer understanding of the crucial role of N- and O-linked carbohydrates in dictating the properties of the proteins to which they are attached and, in particular, their centrality in the control of protein synthesis, longevity, and activity. Given their importance, it is unsurprising that both gross and subtle defects in glycosylation often contribute to human disease pathology. In this review, we discuss the accumulating evidence for the significance of glycosylation in mediating the functions of the plasma glycoproteins involved in hemostasis and thrombosis. In particular, the role of naturally occurring coagulation protein glycoforms and inherited defects in carbohydrate attachment in modulating coagulation is considered. Finally, we describe the therapeutic opportunities presented by new insights into the role of attached carbohydrates in shaping coagulation protein function and the promise of carbohydrate modification in the delivery of novel therapeutic biologics with enhanced functional properties for the treatment of hemostatic disorders.

Download Full-text

Fine structure and properties of defects in naturally occurring silicates and oxides

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100175430 ◽

1990 ◽

Vol 48 (4) ◽

pp. 460-461

Author(s):

David R. Veblen

Keyword(s):

Chemical Reactions ◽

High Resolution Electron Microscopy ◽

Extended Defects ◽

Single Chain ◽

Naturally Occurring ◽

Resolution Electron ◽

Fine Structures ◽

Image Simulations ◽

Similar Crystal Structure

Extended defects and interfaces control many processes in rock-forming minerals, from chemical reactions to rock deformation. In many cases, it is not the average structure of a defect or interface that is most important, but rather the structure of defect terminations or offsets in an interface. One of the major thrusts of high-resolution electron microscopy in the earth sciences has been to identify the role of defect fine structures in reactions and to determine the structures of such features. This paper will review studies using HREM and image simulations to determine the structures of defects in silicate and oxide minerals and present several examples of the role of defects in mineral chemical reactions. In some cases, the geological occurrence can be used to constrain the diffusional properties of defects.The simplest reactions in minerals involve exsolution (precipitation) of one mineral from another with a similar crystal structure, and pyroxenes (single-chain silicates) provide a good example. Although conventional TEM studies have led to a basic understanding of this sort of phase separation in pyroxenes via spinodal decomposition or nucleation and growth, HREM has provided a much more detailed appreciation of the processes involved.

Download Full-text

Simultaneous Occurrence of Human Antibodies Directed against Fibrinogen, Thrombin, and Factor V Following Exposure to Bovine Thrombin: Effects on Blood Coagulation, Protein C Activation and Platelet Function

Thrombosis and Haemostasis ◽

10.1055/s-0038-1655966 ◽

1997 ◽

Vol 77 (02) ◽

pp. 343-349 ◽

Cited By ~ 53

Author(s):

Vibhuti D Chouhan ◽

Raul A De La Cadena ◽

Chandrasekaran Nagaswami ◽

John W Weisel ◽

Mehdi Kajani ◽

...

Keyword(s):

Protein C ◽

Simultaneous Occurrence ◽

Factor V ◽

Bovine Thrombin ◽

Plasma Factor ◽

Coagulation Tests ◽

Coagulation Protein ◽

Severe Epistaxis ◽

Clotting Protein

SummaryWe describe a patient with severe epistaxis, prolonged coagulation tests and decreased plasma factor V following exposure to bovine topical thrombin. Patient IgG, but not normal IgG, showed binding to immobilized thrombin (bovine > human) and fibrinogen, and to factor V by Western blotting; the binding to thrombin was inhibited by hirudin fragment 54-65. Electron microscopy of rotary shadowed preparations showed complexes with IgG molecules attached near the ends of trinodular fibrinogen molecules. Patient IgG inhibited procoagulant, anticoagulant and cell-stimulating functions of thrombin demonstrated by inhibition of fibrinogen clotting, protein C activation and platelet aggregation; thrombin hydrolysis of S-2238 was not inhibited. The results suggest that the antibody is targeted against anion-binding exosite and not catalytic site of thrombin. Antifibrinogen antibodies have not been reported in patients exposed to bovine thrombin. There is a pressing need to re-evaluate the role of bovine thrombin as a therapeutic agent.

Download Full-text

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190916141934 ◽

2019 ◽

Vol 18 (8) ◽

pp. 581-597 ◽

Cited By ~ 1

Author(s):

Ambreen Fatima ◽

Yasir Hasan Siddique

Keyword(s):

Medicinal Plants ◽

Mechanism Of Action ◽

Neurodegenerative Disorders ◽

Treatment Strategies ◽

Dietary Supplementation ◽

Plant Polyphenols ◽

Promising Candidate ◽

Naturally Occurring ◽

The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

Download Full-text

Monosodium Glutamate Toxicity and the Possible Protective Role of L–Carnitine

Science & Technology Journal ◽

10.22232/stj.2018.06.01.06 ◽

2018 ◽

Vol 6 (1) ◽

pp. 45-56

Author(s):

Lalrinzuali Sailo ◽

◽

Meesala Krishna Murthy ◽

Khandayataray Pratima ◽

Vikas Kumar Roy ◽

...

Keyword(s):

Human Subjects ◽

Monosodium Glutamate ◽

Essential Amino Acids ◽

Protective Role ◽

Glutamate Toxicity ◽

Common Salt ◽

Genotoxic Effects ◽

Naturally Occurring ◽

Flavour Enhancer

Monosodium glutamate is naturally available non-essential amino acids, which found in naturally occurring foods and used as flavour enhancer worldwide. Monosodium glutamate is believed to be linked with diverse health problems. The aim of the study was toxic effects of monosodium glutamate (MSG) and the protective role of L-carnitine, light on the available literature from last 25 years about diverse toxicity studies which had been carried out on animal and human models. Google scholar, NCBI, PUBMED, EMBASE, Wangfang databases, and Web of Science databases were used to retrieve the available studies. MSG was linked with deleterious effects particularly in animals including induction of obesity, diabetes, hepatotoxic, neurotoxic and genotoxic effects showed in Literature. Few reports revealed increased hunger, food intake, and obesity in human subjects due to MSG consumption. Hepatotoxic, neurotoxic, and genotoxic effects of monosodium glutamate on humans carried out very limitedly. High consumption of monosodium glutamate may be linked with harmful health effects showed in available literatures. So, it is recommended to use common salt instead of MSG. Furthermore, intensive research is required to explore monosodium glutamate–related molecular and metabolic mechanisms. L-carnitine can protect from Hepatotoxic, neurotoxic, renal impairment and genotoxic effects functionally, biochemically and histopathologically with a corresponding reduction of oxidative stress.

Download Full-text

PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

Cell Death and Disease ◽

10.1038/s41419-021-04013-y ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Dawei Chen ◽

Zhenguo Zhao ◽

Lu Chen ◽

Qinghua Li ◽

Jixue Zou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Alternative Splicing ◽

Protein Function ◽

Vital Role ◽

Normal Tissues ◽

Mechanistic Analysis ◽

Highly Correlated ◽

Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

Download Full-text

How Artefacts Do Leadership: A Ventriloquial Analysis

Management Communication Quarterly ◽

10.1177/0893318921998078 ◽

2021 ◽

pp. 089331892199807

Author(s):

Jonathan Clifton ◽

Fernando Fachin ◽

François Cooren

Keyword(s):

Organizational Communication ◽

Recent Work ◽

Distributed Leadership ◽

Network Theory ◽

Actor Network Theory ◽

Fine Grained ◽

Naturally Occurring ◽

Human Actors

To date there has been little work that uses fine-grained interactional analyses of the in situ doing of leadership to make visible the role of non-human as well as human actants in this process. Using transcripts of naturally-occurring interaction as data, this study seeks to show how leadership is co-achieved by artefacts as an in-situ accomplishment. To do this we situate this study within recent work on distributed leadership and argue that it is not only distributed across human actors, but also across networks that include both human and non-human actors. Taking a discursive approach to leadership, we draw on Actor Network Theory and adopt a ventriloquial approach to sociomateriality as inspired by the Montreal School of organizational communication. Findings indicate that artefacts “do” leadership when a hybrid presence is made relevant to the interaction and when this presence provides authoritative grounds for influencing others to achieve the group’s goals.

Download Full-text

Selenium and Dogs: A Systematic Review

Animals ◽

10.3390/ani11020418 ◽

2021 ◽

Vol 11 (2) ◽

pp. 418

Author(s):

Viola Zentrichová ◽

Alena Pechová ◽

Simona Kovaříková

Keyword(s):

Male Fertility ◽

Clinical Signs ◽

Complex Data ◽

Selenium Status ◽

Dog Food ◽

Balanced Diet ◽

Naturally Occurring ◽

Correct Function ◽

Indirect Assay

The intent of this review is to summarize the knowledge about selenium and its function in a dog’s body. For this purpose, systematic literature search was conducted. For mammals, including dogs, a balanced diet and sufficient intake of selenium are important for correct function of metabolism. As for selenium poisoning, there are no naturally occurring cases known. Nowadays, we do not encounter clinical signs of its deficiency either, but it can be subclinical. For now, the most reliable method of assessing selenium status of a dog is measuring serum or plasma levels. Levels in full blood can be measured too, but there are no reference values. The use of glutathione peroxidase as an indirect assay is questionable in canines. Commercial dog food manufactures follow recommendations for minimal and maximal selenium levels and so dogs fed commercial diets should have balanced intake of selenium. For dogs fed home-made diets, complex data are missing. However, subclinical deficiency seems to affect, for example, male fertility or recovery from parasitical diseases. Very interesting is the role of selenium in prevention and treatment of cancer.

Download Full-text

Arsenic Removal by Advanced Electrocoagulation Processes: The Role of Oxidants Generated and Kinetic Modeling

Catalysts ◽

10.3390/catal10080928 ◽

2020 ◽

Vol 10 (8) ◽

pp. 928

Author(s):

Micah Flor V. Montefalcon ◽

Meliton R. Chiong ◽

Augustus C. Resurreccion ◽

Sergi Garcia-Segura ◽

Joey D. Ocon

Keyword(s):

Kinetic Modeling ◽

Arsenic Removal ◽

Fold Increase ◽

Electrochemical Treatment ◽

Promising Alternative ◽

Iron Electrodes ◽

Removal Capacity ◽

Naturally Occurring ◽

Treatment Technologies

Arsenic (As) is a naturally occurring element in the environment that poses significant risks to human health. Several treatment technologies have been successfully used in the treatment of As-contaminated waters. However, limited literature has explored advanced electrocoagulation (EC) processes for As removal. The present study evaluates the As removal performance of electrocoagulation, electrochemical peroxidation (ECP), and photo-assisted electrochemical peroxidation (PECP) technologies at circumneutral pH using electroactive iron electrodes. The influence of As speciation and the role of oxidants in As removal were investigated. We have identified the ECP process to be a promising alternative for the conventional EC with around 4-fold increase in arsenic removal capacity at a competitive cost of 0.0060 $/m3. Results also indicated that the rate of As(III) oxidation at the outset of electrochemical treatment dictates the extent of As removal. Both ECP and PECP processes reached greater than 96% As(III) conversion at 1 C/L and achieved 86% and 96% As removal at 5 C/L, respectively. Finally, the mechanism of As(III) oxidation was evaluated, and results showed that Fe(IV) is the intermediate oxidant generated in advanced EC processes, and the contribution of •OH brought by UV irradiation is insignificant.

Download Full-text