scholarly journals BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pilar González-Gómez ◽  
Nilson Praia Anselmo ◽  
Helena Mira

Astrocytic glioma is the most common brain tumor. The glioma initiating cell (GIC) fraction of the tumor is considered as highly chemoresistant, suggesting that GICs are responsible for glioma relapse. A potential treatment for glioma is to induce differentiation of GICs to a more benign and/or druggable cell type. Given BMPs are among the most potent inducers of GIC differentiation, they have been considered as noncytotoxic therapeutic compounds that may be of use to prevent growth and recurrence of glioma. We herein summarize advances made in the understanding of the role of BMP signaling in astrocytic glioma, with a particular emphasis on the effects exerted on GICs. We discuss the prognostic value of BMP signaling components and the implications of BMPs in the differentiation of GICs and in their sensitization to alkylating drugs and oncolytic therapy/chemotherapy. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

2021 ◽  
Vol 12 ◽  
Author(s):  
Marcus G. Heisler

Over the last decade or so important progress has been made in identifying and understanding a set of patterning mechanisms that have the potential to explain many aspects of plant morphology. These include the feedback loop between mechanical stresses and interphase microtubules, the regulation of plant cell polarity and the role of adaxial and abaxial cell type boundaries. What is perhaps most intriguing is how these mechanisms integrate in a combinatorial manner that provides a means to generate a large variety of commonly seen plant morphologies. Here, I review our current understanding of these mechanisms and discuss the links between them.


Author(s):  
Petar Halachev ◽  
Victoria Radeva ◽  
Albena Nikiforova ◽  
Miglena Veneva

This report is dedicated to the role of the web site as an important tool for presenting business on the Internet. Classification of site types has been made in terms of their application in the business and the types of structures in their construction. The Models of the Life Cycle for designing business websites are analyzed and are outlined their strengths and weaknesses. The stages in the design, construction, commissioning, and maintenance of a business website are distinguished and the activities and requirements of each stage are specified.


Author(s):  
Stephen Yablo

Aboutness has been studied from any number of angles. Brentano made it the defining feature of the mental. Phenomenologists try to pin down the aboutness features of particular mental states. Materialists sometimes claim to have grounded aboutness in natural regularities. Attempts have even been made, in library science and information theory, to operationalize the notion. However, it has played no real role in philosophical semantics, which is surprising. This is the first book to examine through a philosophical lens the role of subject matter in meaning. A long-standing tradition sees meaning as truth conditions, to be specified by listing the scenarios in which a sentence is true. Nothing is said about the principle of selection—about what in a scenario gets it onto the list. Subject matter is the missing link here. A sentence is true because of how matters stand where its subject matter is concerned. This book maintains that this is not just a feature of subject matter, but its essence. One indicates what a sentence is about by mapping out logical space according to its changing ways of being true or false. The notion of content that results—directed content—is brought to bear on a range of philosophical topics, including ontology, verisimilitude, knowledge, loose talk, assertive content, and philosophical methodology. The book represents a major advance in semantics and the philosophy of language.


2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.


Author(s):  
Amy Strecker

The final chapter of this book advances four main conclusions on the role of international law in landscape protection. These relate to state obligations regarding landscape protection, the influence of the World Heritage Convention and the European Landscape Convention, the substantive and procedural nature of landscape rights, and the role of EU law. It is argued that, although state practice is lagging behind the normative developments made in the field of international landscape protection, landscape has contributed positively to the corpus of international cultural heritage law and indeed has emerged as a nascent field of international law in its own right.


Universe ◽  
2019 ◽  
Vol 5 (12) ◽  
pp. 226 ◽  
Author(s):  
Don Koks

I analyse the role of simultaneity in relativistic rotation by building incrementally on its role in simpler scenarios. Historically, rotation has been analysed in 1 + 1 dimensions; but my stance is that a 2 + 1 -dimensional treatment is necessary. This treatment requires a discussion of what constitutes a frame, how coordinate choices differ from frame choices, and how poor coordinates can be misleading. I determine how precisely we are able to define a meaningful time coordinate on a gravity-free rotating Earth, and discuss complications due to gravity on our real Earth. I end with a critique of several statements made in relativistic precision-timing literature, that I maintain contradict the tenets of relativity. Those statements tend to be made in the context of satellite-based navigation; but they are independent of that technology, and hence are not validated by its success. I suggest that if relativistic precision-timing adheres to such analyses, our civilian timing is likely to suffer in the near future as clocks become ever more precise.


2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li

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.


2021 ◽  
Vol 9 (3) ◽  
pp. 24
Author(s):  
Brian Heubel ◽  
Anja Nohe

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.


2021 ◽  
Vol 2 (2) ◽  
pp. 274-292
Author(s):  
Sarah James ◽  
Edith Joseph

The instability of iron artefacts is rooted in salt contamination during burial and damages associated with exposure to alternative oxygen levels and high relative humidity once excavated. While a combination of chemical and mechanical treatments is utilised to remove the harmful ions (chlorides, sulphur species) and excess bulky corrosion products, these methods can be hazardous for conservation staff’s health, have limited success, or require extensive treatment times. Bio-based treatments provide a potentially greener alternative for removing damaging corrosion and creating biogenic mineral passivation layers, thus remediating concerns over costs, duration, and health and safety. Pseudomonas putida mt-2 (KT2440) is capable of utilising iron under certain conditions and for phosphating mild steel; however, applications have not been made in the cultural heritage sector. To address the potential of using bacteria for conservation purposes, Pseudomonas was assessed for both the bioremediation of salt contaminates and the production of a passivation layer suitable for iron artefacts, with specific conservation concerns in mind. Key factors for optimisation include the role of agitation, chloride content, and oxygen content on bacterial growth and biomineralisation. The initial results indicate a growth preference, not reliance, for NaCl and agitation with partial success of bioconversion of a mineral source.


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