Activation Of Specific Molecules Research Articles

Communication of the Cell Periphery with the Golgi Apparatus: A Hypothesis.

The Golgi apparatus plays a central role in the numerous traffic tasks in cells. Whereas the well-investigated chemical signaling is sufficient to explain the information processes in the secretory output of cells, it is insufficient to do that for the substitution of structural elements in the three-dimensional space of the cell. Here we review recent work (Jaross, Front Biosci 23:940-946, 2018) suggesting that molecular vibration patterns of those macromolecules which have to be exchanged are recognized by molecules in the Golgi via resonance of the electromagnetic fingerprints. That results in the activation of specific molecules and induction of the whole substitution process. For bridging intracellular distances, the IR radiation must be coherent. It is discussed that coherence is achieved by chemical reaction during the changing process of the molecule along with the quasicrystalline structure of the neighboring water molecules. Several aspects of the relevance of that signaling to the direct interactions of molecules during various intracellular processes are discussed.

Molecular imaging of breast cancer: present and future directions.

Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumor is located in the body, but also to visualize the expression and activity of specific molecules (e.g., proteases and protein kinases) and biological processes (e.g., apoptosis, angiogenesis, and metastasis) that influence tumor behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

Endoscopic Molecular Imaging: Status and Future Perspective

During the last decade, researchers have made great progress in the development of new image processing technologies for gastrointestinal endoscopy. However, diagnosis using conventional endoscopy with white light optical imaging is essentially limited, and ultimately, we still rely on the histopathological diagnosis from biopsy specimens. Molecular imaging represents the most novel imaging methods in medicine, and the future of endoscopic diagnosis is likely to be impacted by a combination of biomarkers and technology. Endoscopic molecular imaging can be defined as the visualization of molecular characteristics with endoscopy. These innovations will allow us not only to locate a tumor or dysplastic lesion but also to visualize its molecular characteristics and the activity of specific molecules and biological processes that affect tumor behavior and/or its response to therapy. In the near future, these promising technologies will play a central role in endoluminal oncology.

STATus and Context within the Mammalian Nervous System

Effective manipulation of human disease processes may be achieved by understanding transcriptional, posttranscriptional and epigenetic events that orchestrate cellular events. The levels of activation of specific molecules, spatial distribution and concentrations of relevant networks of signaling molecules along with the receptiveness of the chromatin to these signals are some of the parameters which dictate context. Effects elicited by the transcription factor signal transducers and activator of transcription 3 (Stat3) are discussed with respect to the context within which Stat3-mediated effects are elicited within the developing and adult mammalian nervous system. Stat3 signals are pivotal to the proliferation and differentiation of neural stem cells. They also participate in neuronal regeneration and cancers of the nervous system. An analysis of the context in which Stat3 activation occurs in these processes provides a potential predictive paradigm with which novel methods for intervention may be designed.

Molecular imaging in pediatrics

Medical imaging technology has experienced rapid development over the past several decades, and these innovative developments have transformed radiology, making it an essential “guiding hand” of medical practice. In parallel, the rapid pace of biological advances have made this the age of molecular medicine. Thanks to the emerging field of molecular imaging, the radiology community has the opportunity to help lead a revolution in modern medicine toward optimized diagnosis and therapy in individual patients. Molecular imaging is the in vivo characterization and quantification of biological processes that occur at cellular and molecular level, at a macroscopic level of resolution. This is in contrast to current conventional, anatomically based radiology. Molecular imaging will play a major role in the near future, not only within the scope of basic research, but also in clinical diagnosis and monitoring of therapy. Molecular imaging will not only provide the exact localization of a disease or lesion, but also show the expression and activity of specific molecules (proteases, kinases, etc.) and biological processes (apoptosis, angiogenesis, metastasis, etc.), the behavior of diseases and/or response to therapies. This information is expected to have a major impact on early diagnosis, individualized treatment and the development of new therapies, as well as on the general understanding of how diseases arise. Imaging techniques that fit this description have been in use for a number of years, and include contrastenhanced magnetic resonance imaging, magnetic resonance spectroscopy, single photon emission computed tomography, positron emission tomography, optical imaging, and various combinations of these techniques using multimodality and multiparametric imaging. The clinical use of more specific molecular imaging probes, along with high-throughput serum screening and biologically targeted biopsies, will make it possible to apply a growing array of imaging techniques, including serum and tissue biomarkers, to detect and characterize disease in humans. These will include predictive biomarkers for identifying the relative sensitivity or resistance of a disease to a specific therapy, or for identifying disease that does not require treatment; biomarkers for assessing treatment response earlier than is possible with conventional means; and prognostic biomarkers that provide information about the likely outcome, regardless of the specific treatment applied. In addition, molecular imaging will allow the increasing use of theranostics, i.e. combinations of targeted diagnostic and therapeutic agents that work sequentially or in tandem. Emerging genomic and proteomic technologies have the potential to transform the way in which these diseases are managed clinically. The direction for radiology, as for almost all of modern medicine, is to begin thinking at the molecular level. Although most molecular imaging techniques are used in preclinical or early clinical phases, pediatric radiology will benefit greatly from these methods. Many diseases, especially those with specific molecular fingerprints, including many pediatric diseases, could reap the future advantages that these new techniques will provide, including better detection, characterization, diagnosis, targeted therapies, and the ability to monitor results at molecular level. Molecular imaging is the key technology for accomplishing these goals. Although the challenges are significant, the potential for molecular imaging is enormous. These techniques represent the future of imaging. Disclaimer Dr. Brader has no financial interests, investigational or off-label uses to diclose.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research.

Dopamine‐induced programmed cell death is associated with cytochrome c release and caspase‐3 activation in snail salivary gland cells

PCD (programmed cell death) is a common mechanism to remove unwanted and excessive cells from organisms. In several exocrine cell types, PCD mode of release of secretory products has been reported. The molecular mechanism of the release, however, is largely unknown. Our aim was to study the molecular mechanism of saliva release from cystic cells, the specific cell type of snail SGs (salivary glands). SG cells in active feeding animals revealed multiple morphological changes characteristic of PCD. Nerve stimulation and DA (dopamine) increased the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)-positive cells both in inactive and feeding animals. The DA-induced PCD was prevented by TEA (tetraethylammonium chloride) and eticlopride, emphasizing the role of K channels and D2 receptors in the PCD of cystic cells. DA enhanced cyto-c (cytochrome c) translocation into the cytosol and methyl-beta-cyclodextrin prevented it, suggesting apoptosome formation and ceramide involvement in the PCD linking of the surface DA receptor to mitochondria. Western blot analysis revealed that the release of cyto-c was under the control of Bcl-2 and Bad. DA also increased the active caspase-3 in gland cells while D2 receptor antagonists and TEA attenuated it. Our results provide evidence for a type of transmitter-mediated pathway that regulates the PCD of secretory cells in a mitochondrial-caspase-dependent manner. The activation of specific molecules, such as K channels, DA receptors, cyto-c, ceramide, Bcl-2 proteins and caspase-3, but not caspase-8, was demonstrated in cells involved in the DA-induced PCD, suggesting that PCD is a physiological method for the release of saliva from SG cells.

MRI of Geometric and Compositional Features of Vulnerable Carotid Plaque

Noninvasive imaging of atherosclerotic disease provides a powerful opportunity to gain insight into the complex chain of events underlying atherogenesis, plaque progression, and ultimately those processes that result in atherothrombosis with accompanying clinical symptoms. MRI is particularly attractive because it is noninvasive and is capable of providing a rich array of information on vascular disease. MR methods have been demonstrated to provide information on important features of vascular disease, including the geometric morphology of the flow lumen and the vessel wall, the composition of atheroma, measurement of flow velocities through vessels independent of overlying structures, and more recently insights into the presence and activity of specific molecules that are considered to be important participants in the inflammatory processes and that might differentiate the stable plaque from the vulnerable plaque.

Molecular Imaging in Cancer

Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumor is located in the body, but also to visualize the expression and activity of specific molecules (e.g., proteases and protein kinases) and biological processes (e.g., apoptosis, angiogenesis, and metastasis) that influence tumor behavior and/or response to therapy. This information is expected to have a major impact on cancer detection, individualized treatment, and drug development, as well as our understanding of how cancer arises.

Improving Cancer Therapeutics by Molecular Profiling

The individualized medicine aims to identify the molecular basis of the individual's response to different therapeutic treatments. Individualized medicine is very relevant for human diseases such as cancer and it has become a major task to accomplish more efficient and specific therapeutics. An individualized response to treatment could underline therapeutic success or failure and, even more, could support the rationale for good or bad prognosis. The use of up to date genomic approaches is changing the way we understand modern medicine in terms of drug efficacy, toxicity and diagnosis. Results from genetic polymorphism studies, gene expression profiling and epigenetics illustrate how pharmacogenomic testing will contribute to the goal of individualized medicine. Antineoplastic drugs are designed to block the anomalous activity of specific molecules (therapeutic targets) that regulate cellular processes such as cell cycle. Understanding the relationship between molecular changes in therapeutic targets and enhanced antitumoral response or chemotherapeutic resistance is crucial to establish the clinical relevance of genomic approaches. The goal of this review is to discuss the basic and the clinical significance of genomic research on drug targets and its impact on the early diagnosis and treatment of cancer. We will also assess how these methodologies could contribute to individualized medicine in oncology. A special focus will be put on oncogenes and tumor suppressor genes. Aspects such as drug efficacy, side effects and the diagnostic value of antineoplastic pharmacogenomic research will be also considered.

Effects of perturbation of cell polarity on molecular markers of sperm-egg binding sites on mouse eggs.

The mouse germinal vesicle (GV)-intact oocyte is a symmetric cell, with the GV centrally localized and with components of the plasma membrane and cortex symmetrically distributed around the periphery of the oocyte. During oocyte maturation, two distinct regions of the egg plasma membrane and cortex develop: the amicrovillar region overlying the meiotic spindle and the microvillar region. The development of this polarity is significant, since sperm bind to and fuse with the microvillar region. We are interested in the development of egg polarity and have characterized the localizations of several markers for egg polarity in normal metaphase II eggs and GV-intact oocytes. The asymmetric distributions of these markers (including actin, cortical granules, binding sites for the sperm proteins fertilin alpha and fertilin beta, and two different beta(1) integrin epitopes) develop during oocyte maturation in vitro, and this polarity can be perturbed by treatments that disrupt the actin microfilaments or microtubules. In addition, immunoelectron microscopy reveals that binding sites for recombinant fertilin beta are specifically localized to the microvillar region, suggesting that the binding sites for this sperm ligand are either specifically localized or activated in this region. These results indicate that structural remodeling of the mouse egg plasma membrane is accompanied by molecular remodeling, resulting in the localization or activation of specific molecules in subdomains of the plasma membrane.

Fluorescently labelled molecules as probes of the structure and function of living cells.

A new approach to cell biology has been created by combining the techniques of micromanipulation of cells, fluorescence spectroscopy and low level light detection. These methods are now being used to study the spatial and temporal distribution, interaction and activity of specific molecules in living cells