scholarly journals Targeting mitotic pathways for endocrine-related cancer therapeutics

2017 ◽  
Vol 24 (9) ◽  
pp. T65-T82 ◽  
Author(s):  
Shivangi Agarwal ◽  
Dileep Varma
Keyword(s):  
Cell Cycle ◽  
Chromosomal Instability ◽  
Cancer Therapeutics ◽  
Basic Research ◽  
The Past ◽  
Complex Process ◽  
Selective Interference ◽  
Cell Cycle Deregulation ◽  
Microtubule Poisons ◽  
Made In

A colossal amount of basic research over the past few decades has provided unprecedented insights into the highly complex process of cell division. There is an ever-expanding catalog of proteins that orchestrate, participate and coordinate in the exquisite processes of spindle formation, chromosome dynamics and the formation and regulation of kinetochore microtubule attachments. Use of classical microtubule poisons has still been widely and often successfully used to combat a variety of cancers, but their non-selective interference in other crucial physiologic processes necessitate the identification of novel druggable components specific to the cell cycle/division pathway. Considering cell cycle deregulation, unscheduled proliferation, genomic instability and chromosomal instability as a hallmark of tumor cells, there lies an enormous untapped terrain that needs to be unearthed before a drug can pave its way from bench to bedside. This review attempts to systematically summarize the advances made in this context so far with an emphasis on endocrine-related cancers and the avenues for future progress to target mitotic mechanisms in an effort to combat these dreadful cancers.

Practical implementations for improving the throughput in a manual crystallization setup

2005 ◽  
Vol 38 (3) ◽  
pp. 568-570 ◽  
Author(s):  
Christian Biertümpfel ◽  
Jérôme Basquin ◽  
Dietrich Suck
Keyword(s):  
High Throughput ◽  
Structural Genomics ◽  
Basic Research ◽  
Financial Resources ◽  
The Past ◽  
Financial Investments ◽  
Simple Question ◽  
Speed Up ◽  
Reduction Of Costs ◽  
Made In

For the past few years, the number of structural genomics projects has been growing enormously worldwide. All these projects are supported by substantial financial resources and therefore are able to employ robotics for setting up high-throughput platforms. This paper addresses a simple question: how can basic research laboratories draw profit from the efforts and innovations that have been made to establish high-throughput facilities? To answer this question, the implementations that have been made in the authors' laboratory to improve manual crystallization setup with very limited financial investments are presented. In combination with 96-well microplates, an advanced protocol has been introduced and several simple devices have been designed to speed up different aspects of the manual crystallization setup, from storage of solutions to the setting of drops. These implementations lead to the reduction of costs in terms of time and money without any loss of quality. In addition, the crystallization throughput in the manual setup has been significantly increased.

scholarly journals Tooth Bioengineering and Regenerative Dentistry

2019 ◽  
Vol 98 (11) ◽  
pp. 1173-1182 ◽  
Author(s):  
P.C. Yelick ◽  
P.T. Sharpe
Keyword(s):  
Tissue Engineering ◽  
Current Knowledge ◽  
Basic Research ◽  
Dental Tissue ◽  
Dental Tissues ◽  
The Past ◽  
Tremendous Progress ◽  
Regenerative Dentistry ◽  
Dental Tissue Engineering ◽  
Made In

Over the past 100 y, tremendous progress has been made in the fields of dental tissue engineering and regenerative dental medicine, collectively known as translational dentistry. Translational dentistry has benefited from the more mature field of tissue engineering and regenerative medicine (TERM), established on the belief that biocompatible scaffolds, cells, and growth factors could be used to create functional, living replacement tissues and organs. TERM, created and pioneered by an interdisciplinary group of clinicians, biomedical engineers, and basic research scientists, works to create bioengineered replacement tissues that provide at least enough function for patients to survive until donor organs are available and, at best, fully functional replacement organs. Ultimately, the goal of both TERM and regenerative dentistry is to bring new and more effective therapies to the clinic to treat those in need. Very recently, the National Institutes of Health/National Institute of Dental and Craniofacial Research invested $24 million over a 3-y period to create dental oral and craniofacial translational resource centers to facilitate the development of more effective therapies to treat edentulism and other dental-related diseases over the next decade. This exciting era in regenerative dentistry, particularly for whole-tooth tissue engineering, builds on many key successes over the past 100 y that have contributed toward our current knowledge and understanding of signaling pathways directing natural tooth and dental tissue development—the foundation for current strategies to engineer functional, living replacement dental tissues and whole teeth. Here we use a historical perspective to present key findings and pivotal advances made in the field of translational dentistry over the past 100 y. We will first describe how this process has evolved over the past 100 y and then hypothesize on what to expect over the next century.

Hydraulic Laboratory at University of Liège

2018 ◽  
pp. 80-89
Author(s):  
Willi H. Hager
Keyword(s):  
Basic Research ◽  
The Novel ◽  
University Campus ◽  
Current Position ◽  
Professional Background ◽  
The Past ◽  
Comprehensive Picture

The Hydraulic Laboratory of Liège University, Belgium, is historically considered from its foundation in 1937 to the mid-1960s. The technical facilities of the various Buildings are highlighted, along with canals and instrumentation available. It is noted that in its initial era, comparatively few basic research has been conducted, mainly due to the professional background of the professors leading the establishment. This state was improved in the past 50 years, however, particularly since the Laboratory was dislocated to its current position in the novel University Campus. Biographies of the leading persons associated with the Liège Hydraulic Laboratory are also presented, so that a comprehensive picture is given of one of the currently leading hydraulic Laboratories of Europe.

South Asian Developmental Crisis (Review Article)

1973 ◽  
Vol 12 (2) ◽  
pp. 181-188
Author(s):  
Rafiq Ahmad
Keyword(s):  
Second World War ◽  
World War ◽  
The Past ◽  
The Great Depression ◽  
Political Independence ◽  
Integrated Theory ◽  
Pass Through ◽  
Developed World ◽  
Second World ◽  
Made In

Like nations and civilizations, sciences also pass through period of crises when established theories are overthrown by the unpredictable behaviour of events. Economics is passing through such a crisis. The challenge thrown by the Great Depression of early 1930s took a decade before Keynes re-established the supremacy of economics. But this supremacy has again been upset by the crisis of poverty in the vast under-developed world which attained political independence after the Second World War. Poverty had always existed but never before had it been of such concern to economists as during the past twenty five years or so. Economic literature dealing with this problem has piled up but so have the agonies of poverty. No plausible and well-integrated theory of economic development or under-development has emerged so far, though brilliant advances have been made in isolated directions.

Mass Spectrometry Techniques: Principles and Practices for Quantitative Proteomics

2020 ◽  
Vol 21 ◽  
Author(s):  
Rocco J. Rotello ◽  
Timothy D. Veenstra
Keyword(s):  
Mass Spectrometry ◽  
Quantitative Proteomics ◽  
Protein Identification ◽  
Dynamic Nature ◽  
Complete Coverage ◽  
The Past ◽  
Proteome Level ◽  
A Cell ◽  
Quantitative Changes ◽  
Made In

: In the current omics-age of research, major developments have been made in technologies that attempt to survey the entire repertoire of genes, transcripts, proteins, and metabolites present within a cell. While genomics has led to a dramatic increase in our understanding of such things as disease morphology and how organisms respond to medications, it is critical to obtain information at the proteome level since proteins carry out most of the functions within the cell. The primary tool for obtaining proteome-wide information on proteins within the cell is mass spectrometry (MS). While it has historically been associated with the protein identification, developments over the past couple of decades have made MS a robust technology for protein quantitation as well. Identifying quantitative changes in proteomes is complicated by its dynamic nature and the inability of any technique to guarantee complete coverage of every protein within a proteome sample. Fortunately, the combined development of sample preparation and MS methods have made it capable to quantitatively compare many thousands of proteins obtained from cells and organisms.

Evidence-based Assessment

2010 ◽  
pp. 76-98
Author(s):  
John Hunsley ◽  
Eric J. Mash
Keyword(s):  
Decision Making ◽  
Clinical Assessment ◽  
Assessment Process ◽  
Evidence Based ◽  
The Past ◽  
Specific Assessment ◽  
The Many ◽  
Selection Of ◽  
Made In

Evidence-based assessment relies on research and theory to inform the selection of constructs to be assessed for a specific assessment purpose, the methods and measures to be used in the assessment, and the manner in which the assessment process unfolds. An evidence-based approach to clinical assessment necessitates the recognition that, even when evidence-based instruments are used, the assessment process is a decision-making task in which hypotheses must be iteratively formulated and tested. In this chapter, we review (a) the progress that has been made in developing an evidence-based approach to clinical assessment in the past decade and (b) the many challenges that lie ahead if clinical assessment is to be truly evidence-based.

scholarly journals Cytokinin N-glucosides: Occurrence, Metabolism and Biological Activities in Plants

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 24
Author(s):  
Eva Pokorná ◽  
Tomáš Hluska ◽  
Petr Galuszka ◽  
H. Tucker Hallmark ◽  
Petre I. Dobrev ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Growth And Development ◽  
Biological Activities ◽  
Physiological Effects ◽  
Inhibitory Effects ◽  
Plant Growth And Development ◽  
The Past ◽  
Complex Process ◽  
Considerable Impact ◽  
Physiological Impact

Cytokinins (CKs) are a class of phytohormones affecting many aspects of plant growth and development. In the complex process of CK homeostasis in plants, N-glucosylation represents one of the essential metabolic pathways. Its products, CK N7- and N9-glucosides, have been largely overlooked in the past as irreversible and inactive CK products lacking any relevant physiological impact. In this work, we report a widespread distribution of CK N-glucosides across the plant kingdom proceeding from evolutionary older to younger plants with different proportions between N7- and N9-glucosides in the total CK pool. We show dramatic changes in their profiles as well as in expression levels of the UGT76C1 and UGT76C2 genes during Arabidopsis ontogenesis. We also demonstrate specific physiological effects of CK N-glucosides in CK bioassays including their antisenescent activities, inhibitory effects on root development, and activation of the CK signaling pathway visualized by the CK-responsive YFP reporter line, TCSv2::3XVENUS. Last but not least, we present the considerable impact of CK N7- and N9-glucosides on the expression of CK-related genes in maize and their stimulatory effects on CK oxidase/dehydrogenase activity in oats. Our findings revise the apparent irreversibility and inactivity of CK N7- and N9-glucosides and indicate their involvement in CK evolution while suggesting their unique function(s) in plants.

Deregulation of cell cycle and related microRNA expression induced by vinyl chloride monomer in hepatocytes of rats

2021 ◽  
pp. 074823372110155
Author(s):  
Weizhe Pan ◽  
Shengnan Yu ◽  
Jin Jia ◽  
Junyang Hu ◽  
Liang Jie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vinyl Chloride ◽  
Male Rats ◽  
Cell Cycle Distribution ◽  
Vinyl Chloride Monomer ◽  
Dynamic Changes ◽  
Cell Cycle Deregulation ◽  
Change Dynamic ◽  
Related Proteins

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.

The Role of Histones and Heparin in Sepsis: A Review

2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li
Keyword(s):  
Septic Shock ◽  
Multiple Organ ◽  
Clinical Settings ◽  
The Past ◽  
Life Saving ◽  
Extracellular Histones ◽  
Sepsis And Septic Shock ◽  
Development And Management ◽  
Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

scholarly journals Sphingolipid lysosomal storage diseases: from bench to bedside

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Muna Abed Rabbo ◽  
Yara Khodour ◽  
Laurie S. Kaguni ◽  
Johnny Stiban
Keyword(s):  
Basic Research ◽  
Lysosomal Storage Diseases ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Late Nineteenth Century ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
The Past ◽  
Health And Disease ◽  
General Aspects

AbstractJohann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.

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