In vivo cell biology in zebrafish – providing insights into vertebrate development and disease

PubMed Central

Vacaru, Ana M.; Unlu, Gokhan; Spitzner, Marie; Mione, Marina; Knapik, Ela W.; Sadler, Kirsten C.

2014-01-01

ABSTRACT Over the past decades, studies using zebrafish have significantly advanced our understanding of the cellular basis for development and human diseases. Zebrafish have rapidly developing transparent embryos that allow comprehensive imaging of embryogenesis combined with powerful genetic approaches. However, forward genetic screens in zebrafish have generated unanticipated findings that are mirrored by human genetic studies: disruption of genes implicated in basic cellular processes, such as protein secretion or cytoskeletal dynamics, causes discrete developmental or disease phenotypes. This is surprising because many processes that were assumed to be fundamental to the function and survival of all cell types appear instead to be regulated by cell-specific mechanisms. Such discoveries are facilitated by experiments in whole animals, where zebrafish provides an ideal model for visualization and manipulation of organelles and cellular processes in a live vertebrate. Here, we review well-characterized mutants and newly developed tools that underscore this notion. We focus on the secretory pathway and microtubule-based trafficking as illustrative examples of how studying cell biology in vivo using zebrafish has broadened our understanding of the role fundamental cellular processes play in embryogenesis and disease. PMID:24481493

Microscopy basics and the study of actin-actin-binding protein interactions.

PubMed

Thomasson, Maggie S; Macnaughtan, Megan A

2013-12-15

Actin is a multifunctional eukaryotic protein with a globular monomer form that polymerizes into a thin, linear microfilament in cells. Through interactions with various actin-binding proteins (ABPs), actin plays an active role in many cellular processes, such as cell motility and structure. Microscopy techniques are powerful tools for determining the role and mechanism of actin-ABP interactions in these processes. In this article, we describe the basic concepts of fluorescent speckle microscopy, total internal reflection fluorescence microscopy, atomic force microscopy, and cryoelectron microscopy and review recent studies that utilize these techniques to visualize the binding of actin with ABPs. Copyright © 2013 Elsevier Inc. All rights reserved.

B-Catenin Stability in Breast Cancer

DTIC Science & Technology

1996-07-01

like age or family history. In this grim scenario, a basic understanding of the cellular processes underlying breast cancer is mandated before...the ventral region of Xenopus embryos induces a secondary dorso-anterior body axis, giving rise to two heads, notochords , and neural tubes (24). Wnt...pathway is involved in the processing and rapid degradation of many short-lived regulatory proteins. Mitotic cyclins, cyclin-dependent kinase

B-Catenin Stability in Breast Cancer

DTIC Science & Technology

1997-07-01

basic understanding of the cellular processes underlying breast cancer is mandated before effective therapies can be developed or even attempted. P3...Z dorso-anterior body axis, giving rise to two heads, notochords , and neural tubes (24). Wnt-1, dsh dsh hanqgg the vertebrate homologue of wingless is...stability by the ubiquitin-proteasome pathway. The ubiquitin-proteasome pathway is involved in the processing and rapid degradation of many short-lived

Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory

ERIC Educational Resources Information Center

Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

2010-01-01

A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

Riding the Waves: How Our Cells Send Signals | Center for Cancer Research

Cancer.gov

The ability of cells to perceive and respond to their environment is critical in order to maintain basic cellular functions such as development, tissue repair, and response to stress. This process happens through a complex system of communication, called cell signaling, which governs basic cellular activities and coordinates cell actions. Errors in cell signaling have been linked to numerous diseases, including cancer. NF-κB is a protein complex that plays a critical role in many cell signaling pathways by controlling gene activation. It is widely used by cells to regulate cell growth and survival and helps to protect the cell from conditions that would otherwise cause it to die. Many tumor cells have mutations in genes that cause NF-κB to become overactive. Blocking NF-κB could cause tumor cells to stop growing, die, or become more sensitive to therapeutics.

Disruptive chemicals, senescence and immortality

PubMed Central

Carnero, Amancio; Blanco-Aparicio, Carmen; Kondoh, Hiroshi; Lleonart, Matilde E.; Martinez-Leal, Juan Fernando; Mondello, Chiara; Ivana Scovassi, A.; Bisson, William H.; Amedei, Amedeo; Roy, Rabindra; Woodrick, Jordan; Colacci, Annamaria; Vaccari, Monica; Raju, Jayadev; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Salem, Hosni K.; Memeo, Lorenzo; Forte, Stefano; Singh, Neetu; Hamid, Roslida A.; Ryan, Elizabeth P.; Brown, Dustin G.; Wise, John Pierce; Wise, Sandra S.; Yasaei, Hemad

2015-01-01

Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated ‘selection and succession’ of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of ‘driver mutations’ enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes. PMID:26106138

Acceleration of Apoptosis by Extracellular Basic pH in a 3D Human Skin Equivalent System.

PubMed

Park, Gunhyuk; Oh, Dal-Seok; Kim, Yong-Ung; Park, Moon Ki

2017-01-01

Previously, we have shown that extracellular basic pH plays a significant role in both the direct and indirect regulation of cellular processes in a wound; this in turn affects the wound-healing process. Several studies have demonstrated the importance of apoptosis modulation in the wound-healing process, especially in removing inflammatory cells and in inhibiting scar formation. However, the effects of extracellular basic pH on wound healing-related skin damage are yet to be examined. Therefore, we investigated the induction of accelerated apoptosis by extracellular basic pH in skin. Apoptosis-related protein levels were measured using an array kit, target protein expression levels were detected by immunostaining, lactate dehydrogenase was analyzed spectrophotometrically, and Annexin V levels were measured by fluorescence staining. Basic pH (8.40) strongly upregulated extrinsic apoptosis proteins (Fas, high temperature requirement A, and p21) and slightly upregulated intrinsic apoptosis proteins (cytochrome c, B-cell lymphoma 2 [Bcl-2], Bcl-2-associated death promoter, and Bcl-2-like protein 4) in a 3D human skin equivalent system. Moreover, basic pH (8.40) induced heat shock protein (HSP) 60 and 70. In addition, basic pH-exposed Fas- and HSP60-knockdown cells showed significantly decreased levels of apoptosis. Taken together, these results indicate that extracellular basic pH increases early-stage apoptosis through Fas/FasL via modulation of HSP60 and HSP70. © 2017 S. Karger AG, Basel.

Chromatin in embryonic stem cell neuronal differentiation.

PubMed

Meshorer, E

2007-03-01

Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

From Purines to Basic Biochemical Concepts: Experiments for High School Students

ERIC Educational Resources Information Center

Marini, Isabella; Ipata, Piero Luigi

2007-01-01

Many high school biology courses address mainly the molecular and cellular basis of life. The complexity that underlies the most essential processes is often difficult for the students to understand; possibly, in part, because of the inability to see and explore them. Six simple practical experiments on purine catabolism as a part of a…

An Inquiry-Based Practical for a Large, Foundation-Level Undergraduate Laboratory that Enhances Student Understanding of Basic Cellular Concepts and Scientific Experimental Design

ERIC Educational Resources Information Center

Bugarcic, A.; Zimbardi, K.; Macaranas, J.; Thorn, P.

2012-01-01

Student-centered education involving research experiences or inquiry have been shown to help undergraduate students understand, and become excited about, the process of scientific investigation. These benefits are particularly important for students in the early stages of their degree (Report and Kenny,…

[Longevity control in fungi and other organisms. The conception of scales].

PubMed

Mazheĭka, I S; Kudriavtseva, O A; Kamzolkina, O V

2011-01-01

The review deals mainly with gerontological processes that occur on the cellular-colonial level of organization in fungi and cellular-tissular level in other organisms. Aging and anti-aging mechanisms operating on these levels of organization can be considered as common ones for all living things. Fungi, as an object with tissular-like organization of thallus, afford a broad spectrum of possibilities as to solving the tasks of general gerontological import. Three basic (chronological, replicative, and cell-suicidal) and several auxiliary mechanisms of aging are singled out, the classification is given of stochastic aging factors accumulating in cells. It is shown that in complex multi-cellular organisms, aging and anti-aging mechanisms operate on the level of interactions between tissues, though in the base of their actions lie the aforesaid conservative basic mechanisms. Preliminary generalized conception of aging--the conception of scales--is put forward that is founded on the model of balanced and non-balanced counteractions between stressful impacts and various mechanisms of aging and anti-aging with different extent of genetic preprogramming. The importance is reaffirmed of mycological gerontology contribution to broadening of inferences on aging nature.

Preface: cardiac control pathways: signaling and transport phenomena.

PubMed

Sideman, Samuel

2008-03-01

Signaling is part of a complex system of communication that governs basic cellular functions and coordinates cellular activity. Transfer of ions and signaling molecules and their interactions with appropriate receptors, transmembrane transport, and the consequent intracellular interactions and functional cellular response represent a complex system of interwoven phenomena of transport, signaling, conformational changes, chemical activation, and/or genetic expression. The well-being of the cell thus depends on a harmonic orchestration of all these events and the existence of control mechanisms that assure the normal behavior of the various parameters involved and their orderly expression. The ability of cells to sustain life by perceiving and responding correctly to their microenvironment is the basis for development, tissue repair, and immunity, as well as normal tissue homeostasis. Natural deviations, or human-induced interference in the signaling pathways and/or inter- and intracellular transport and information transfer, are responsible for the generation, modulation, and control of diseases. The present overview aims to highlight some major topics of the highly complex cellular information transfer processes and their control mechanisms. Our goal is to contribute to the understanding of the normal and pathophysiological phenomena associated with cardiac functions so that more efficient therapeutic modalities can be developed. Our objective in this volume is to identify and enhance the study of some basic passive and active physical and chemical transport phenomena, physiological signaling pathways, and their biological consequences.

In vivo dynamical behavior of yeast chromatin modeled as an entangled polymer network with constraint release

NASA Astrophysics Data System (ADS)

Wang, Chenxi; Kilfoil, Maria L.

2013-03-01

The high fidelity segregation of chromatin is the central problem in cell mitosis. The role of mechanics underlying this, however, is undetermined. Work in this area has largely focused on cytoskeletal elements of the process. Preliminary work in our lab suggests the mechanical properties of chromatin are fundamental in this process. Nevertheless, the mechanical properties of chromatin in the cellular context are not well-characterized. For better understanding of the role of mechanics in this cellular process, and of the chromatin mechanics in vivo generally, a systematic dynamical description of chromatin in vivo is required. Accordingly, we label specific sites on chromatin with fluorescent proteins of different wave lengths, enabling us to detect multiple spots separately in 3D and track their displacements in time inside living yeast cells. We analyze the pairwise cross-correlated motion between spots as a function of relative distance along the DNA contour. Comparison between the reptation model and our data serves to test our conjecture that chromatin in the cell is basically an entangled polymer network under constraints to thermal motion, and removal of constraints by non-thermal cellular processes is expected to affect its dynamic behavior.

Emerging role of Twist1 in fibrotic diseases.

PubMed

Ning, Xiaoxuan; Zhang, Kun; Wu, Qingfeng; Liu, Minna; Sun, Shiren

2018-03-01

Epithelial-mesenchymal transition (EMT) is a pathological process that occurs in a variety of diseases, including organ fibrosis. Twist1, a basic helix-loop-helix transcription factor, is involved in EMT and plays significant roles in various fibrotic diseases. Suppression of the EMT process represents a promising approach for the treatment of fibrotic diseases. In this review, we discuss the roles and the underlying molecular mechanisms of Twist1 in fibrotic diseases, including those affecting kidney, lung, skin, oral submucosa and other tissues. We aim at providing new insight into the pathogenesis of various fibrotic diseases and facilitating the development of novel diagnostic and therapeutic methods for their treatment. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

From drug to protein: using yeast genetics for high-throughput target discovery.

PubMed

Armour, Christopher D; Lum, Pek Yee

2005-02-01

The budding yeast Saccharomyces cerevisiae has long been an effective eukaryotic model system for understanding basic cellular processes. The genetic tractability and ease of manipulation in the laboratory make yeast well suited for large-scale chemical and genetic screens. Several recent studies describing the use of yeast genetics for high-throughput drug target identification are discussed in this review.

Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability.

PubMed

Robic, Srebrenka

2010-01-01

To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability.

The basics of epithelial-mesenchymal transition.

PubMed

Kalluri, Raghu; Weinberg, Robert A

2009-06-01

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

Disruptive chemicals, senescence and immortality.

PubMed

Carnero, Amancio; Blanco-Aparicio, Carmen; Kondoh, Hiroshi; Lleonart, Matilde E; Martinez-Leal, Juan Fernando; Mondello, Chiara; Scovassi, A Ivana; Bisson, William H; Amedei, Amedeo; Roy, Rabindra; Woodrick, Jordan; Colacci, Annamaria; Vaccari, Monica; Raju, Jayadev; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Salem, Hosni K; Memeo, Lorenzo; Forte, Stefano; Singh, Neetu; Hamid, Roslida A; Ryan, Elizabeth P; Brown, Dustin G; Wise, John Pierce; Wise, Sandra S; Yasaei, Hemad

2015-06-01

Carcinogenesis is thought to be a multistep process, with clonal evolution playing a central role in the process. Clonal evolution involves the repeated 'selection and succession' of rare variant cells that acquire a growth advantage over the remaining cell population through the acquisition of 'driver mutations' enabling a selective advantage in a particular micro-environment. Clonal selection is the driving force behind tumorigenesis and possesses three basic requirements: (i) effective competitive proliferation of the variant clone when compared with its neighboring cells, (ii) acquisition of an indefinite capacity for self-renewal, and (iii) establishment of sufficiently high levels of genetic and epigenetic variability to permit the emergence of rare variants. However, several questions regarding the process of clonal evolution remain. Which cellular processes initiate carcinogenesis in the first place? To what extent are environmental carcinogens responsible for the initiation of clonal evolution? What are the roles of genotoxic and non-genotoxic carcinogens in carcinogenesis? What are the underlying mechanisms responsible for chemical carcinogen-induced cellular immortality? Here, we explore the possible mechanisms of cellular immortalization, the contribution of immortalization to tumorigenesis and the mechanisms by which chemical carcinogens may contribute to these processes. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Small Molecule Docking from Theoretical Structural Models

NASA Astrophysics Data System (ADS)

Novoa, Eva Maria; de Pouplana, Lluis Ribas; Orozco, Modesto

Structural approaches to rational drug design rely on the basic assumption that pharmacological activity requires, as necessary but not sufficient condition, the binding of a drug to one or several cellular targets, proteins in most cases. The traditional paradigm assumes that drugs that interact only with a single cellular target are specific and accordingly have little secondary effects, while promiscuous molecules are more likely to generate undesirable side effects. However, current examples indicate that often efficient drugs are able to interact with several biological targets [1] and in fact some dirty drugs, such as chlorpromazine, dextromethorphan, and ibogaine exhibit desired pharmacological properties [2]. These considerations highlight the tremendous difficulty of designing small molecules that both have satisfactory ADME properties and the ability of interacting with a limited set of target proteins with a high affinity, avoiding at the same time undesirable interactions with other proteins. In this complex and challenging scenario, computer simulations emerge as the basic tool to guide medicinal chemists during the drug discovery process.

The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases.

PubMed

Yin, Jinghua; Zhang, Jian; Lu, Qianjin

2017-07-01

Basic leucine zipper transcription factor E4BP4 (also known as NFIL3) has been implicated in the molecular and cellular mechanisms of functions and activities in mammals. The interactions between E4BP4 and major regulators of cellular processes have triggered significant interest in the roles of E4BP4 in the pathogenesis of certain chronic diseases. Indeed, novel discoveries have been emerging to illustrate the involvement of E4BP4 in multiple disorders. It is recognized that E4BP4 is extensively involved in some immune-mediated diseases, but the mechanisms of E4BP4 involvement in these complex diseases remain poorly defined. Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies. Copyright © 2017. Published by Elsevier Inc.

A quantitative study of exocytosis of titanium dioxide nanoparticles from neural stem cells

NASA Astrophysics Data System (ADS)

Wang, Yanli; Wu, Qiuxia; Sui, Keke; Chen, Xin-Xin; Fang, Jie; Hu, Xuefeng; Wu, Minghong; Liu, Yuanfang

2013-05-01

Nanoparticles (NPs) have been widely studied and applied in biomedicine and other fields. It is important to know the basic process of interaction between NPs and cells in terms of cellular endocytosis and exocytosis. However, little attention has been paid to the cellular exocytosis of NPs. Herein, using a multi-step cellular subculture method, we ascertain quantitatively the endocytosis and exocytosis of widely used TiO2 NPs using the neural stem cells (NSC) as a cellular model and ICP-AES as an analytic measure. Irrespective of the type and dose of TiO2 NPs, approximately 30% of the total TiO2 NPs entered NSCs after 48 h incubation. In the first 24 h after removing TiO2NPs, from the culture medium, about 35.0%, 34.6% and 41.7% of NP1 (50 nm), NP2 (30 nm) and NTs (nanotubes, 100 nm × 4-6 nm) were released (exocytosed) from cells, respectively. The release decreased over time, and became negligible at 72 h. Exocytosis did not happen during cell division. In addition, our results suggested that both endocytosis and exocytosis of TiO2NPs were energy-dependent processes, and NPs uptake by cells was influenced by serum proteins. Furthermore, we achieved primary dynamic confocal imaging of the exocytosis, allowing tracking of TiO2 NPs from NSCs. These findings may benefit studies on nanotoxicology and nanomedicine of TiO2 NPs.Nanoparticles (NPs) have been widely studied and applied in biomedicine and other fields. It is important to know the basic process of interaction between NPs and cells in terms of cellular endocytosis and exocytosis. However, little attention has been paid to the cellular exocytosis of NPs. Herein, using a multi-step cellular subculture method, we ascertain quantitatively the endocytosis and exocytosis of widely used TiO2 NPs using the neural stem cells (NSC) as a cellular model and ICP-AES as an analytic measure. Irrespective of the type and dose of TiO2 NPs, approximately 30% of the total TiO2 NPs entered NSCs after 48 h incubation. In the first 24 h after removing TiO2NPs, from the culture medium, about 35.0%, 34.6% and 41.7% of NP1 (50 nm), NP2 (30 nm) and NTs (nanotubes, 100 nm × 4-6 nm) were released (exocytosed) from cells, respectively. The release decreased over time, and became negligible at 72 h. Exocytosis did not happen during cell division. In addition, our results suggested that both endocytosis and exocytosis of TiO2NPs were energy-dependent processes, and NPs uptake by cells was influenced by serum proteins. Furthermore, we achieved primary dynamic confocal imaging of the exocytosis, allowing tracking of TiO2 NPs from NSCs. These findings may benefit studies on nanotoxicology and nanomedicine of TiO2 NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00796k

Students Fail to Transfer Knowledge of Chromosome Structure to Topics Pertaining to Cell Division

PubMed Central

Newman, Dina L.; Catavero, Christina M.; Wright, L. Kate

2012-01-01

Cellular processes that rely on knowledge of molecular behavior are difficult for students to comprehend. For example, thorough understanding of meiosis requires students to integrate several complex concepts related to chromosome structure and function. Using a grounded theory approach, we have unified classroom observations, assessment data, and in-depth interviews under the theory of knowledge transfer to explain student difficulties with concepts related to chromosomal behavior. In this paper, we show that students typically understand basic chromosome structure but do not activate cognitive resources that would allow them to explain macromolecular phenomena (e.g., homologous pairing during meiosis). To improve understanding of topics related to genetic information flow, we suggest that instructors use pedagogies and activities that prime students for making connections between chromosome structure and cellular processes. PMID:23222838

Zebrafish: An Important Tool for Liver Disease Research

PubMed Central

Goessling, Wolfram; Sadler, Kirsten C.

2016-01-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

Sordaria macrospora, a model organism to study fungal cellular development.

PubMed

Engh, Ines; Nowrousian, Minou; Kück, Ulrich

2010-12-01

During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

Cellular automata and its applications in protein bioinformatics.

PubMed

Xiao, Xuan; Wang, Pu; Chou, Kuo-Chen

2011-09-01

With the explosion of protein sequences generated in the postgenomic era, it is highly desirable to develop high-throughput tools for rapidly and reliably identifying various attributes of uncharacterized proteins based on their sequence information alone. The knowledge thus obtained can help us timely utilize these newly found protein sequences for both basic research and drug discovery. Many bioinformatics tools have been developed by means of machine learning methods. This review is focused on the applications of a new kind of science (cellular automata) in protein bioinformatics. A cellular automaton (CA) is an open, flexible and discrete dynamic model that holds enormous potentials in modeling complex systems, in spite of the simplicity of the model itself. Researchers, scientists and practitioners from different fields have utilized cellular automata for visualizing protein sequences, investigating their evolution processes, and predicting their various attributes. Owing to its impressive power, intuitiveness and relative simplicity, the CA approach has great potential for use as a tool for bioinformatics.

Geocoded data structures and their applications to Earth science investigations

NASA Technical Reports Server (NTRS)

Goldberg, M.

1984-01-01

A geocoded data structure is a means for digitally representing a geographically referenced map or image. The characteristics of representative cellular, linked, and hybrid geocoded data structures are reviewed. The data processing requirements of Earth science projects at the Goddard Space Flight Center and the basic tools of geographic data processing are described. Specific ways that new geocoded data structures can be used to adapt these tools to scientists' needs are presented. These include: expanding analysis and modeling capabilities; simplifying the merging of data sets from diverse sources; and saving computer storage space.

Examining the process of de novo gene birth: an educational primer on "integration of new genes into cellular networks, and their structural maturation".

PubMed

Frietze, Seth; Leatherman, Judith

2014-03-01

New genes that arise from modification of the noncoding portion of a genome rather than being duplicated from parent genes are called de novo genes. These genes, identified by their brief evolution and lack of parent genes, provide an opportunity to study the timeframe in which emerging genes integrate into cellular networks, and how the characteristics of these genes change as they mature into bona fide genes. An article by G. Abrusán provides an opportunity to introduce students to fundamental concepts in evolutionary and comparative genetics and to provide a technical background by which to discuss systems biology approaches when studying the evolutionary process of gene birth. Basic background needed to understand the Abrusán study and details on comparative genomic concepts tailored for a classroom discussion are provided, including discussion questions and a supplemental exercise on navigating a genome database.

Ultraweak photon emission in the brain.

PubMed

Salari, V; Valian, H; Bassereh, H; Bókkon, I; Barkhordari, A

2015-09-01

Besides the low-frequency electromagnetic body-processes measurable through the electroencephalography (EEG), electrocardiography (ECG), etc. there are processes that do not need external excitation, emitting light within or close to the visible spectra. Such ultraweak photon emission (UPE), also named biophoton emission, reflects the cellular (and body) oxidative status. Recently, a growing body of evidence shows that UPE may play an important role in the basic functioning of living cells. Moreover, interesting evidences are beginning to emerge that UPE may well play an important role in neuronal functions. In fact, biophotons are byproducts in cellular metabolism and produce false signals (e.g., retinal discrete dark noise) but on the other side neurons contain many light sensitive molecules that makes it hard to imagine how they might not be influenced by UPE, and thus UPE may carry informational contents. Here, we investigate UPE in the brain from different points of view such as experimental evidences, theoretical modeling, and physiological significance.

Role of Integrin in Mechanical Loading of Osteoblasts

NASA Technical Reports Server (NTRS)

Globus, Ruth; Demsky, Caroline

2000-01-01

Mechanical forces generated by gravity, weightbearing, and muscle contraction play a key role in the genesis and maintenance of skeletal structure. The molecular mechanisms that mediate changes in osteoblast activity in response to altered patterns of skeletal loading are not known, and a better understanding of these processes may be essential for developing effective treatment strategies to prevent disuse osteoporosis. We have elucidated specific integrin/ECM (extracellular matrix) interactions that are required for osteoblast differentiation and survival and have developed a useful loading system to further explore the molecular basis of mechano-sensitivity of osteoblasts. The long term goal of our collaborative research is to understand how the ECM and cell adhesion proteins and integrins interaction to mediate the response of osteoblasts and their progenitors to mechanical loading. We suggest that integrin/ECM interactions are crucial for basic cellular processes, including differentiation and survival, as well as to participate in detecting and mediating cellular responses to mechanical stimuli.

Neurobiological Mechanisms for the Regulation of Mammalian Sleep-Wake Behavior: Reinterpretation of Historical Evidence and Inclusion of Contemporary Cellular and Molecular Evidence

PubMed Central

Datta, Subimal; MacLean, Robert Ross

2007-01-01

At its most basic level, the function of mammalian sleep can be described as a restorative process of the brain and body; recently, however, progressive research has revealed a host of vital functions to which sleep is essential. Although many excellent reviews on sleep behavior have been published, none have incorporated contemporary studies examining the molecular mechanisms that govern the various stages of sleep. Utilizing a holistic approach, this review is focused on the basic mechanisms involved in the transition from wakefulness, initiation of sleep and the subsequent generation of slow-wave sleep and rapid eye movement (REM) sleep. Additionally, using recent molecular studies and experimental evidence that provides a direct link to sleep as a behavior, we have developed a new model, the Cellular-Molecular-Network model, explaining the mechanisms responsible for regulating REM sleep. By analyzing the fundamental neurobiological mechanisms responsible for the generation and maintenance of sleep-wake behavior in mammals, we intend to provide a broader understanding of our present knowledge in the field of sleep research. PMID:17445891

A scientific role for Space Station Freedom: Research at the cellular level

NASA Technical Reports Server (NTRS)

Johnson, Terry C.; Brady, John N.

1993-01-01

The scientific importance of Space Station Freedom is discussed in light of the valuable information that can be gained in cellular and developmental biology with regard to the microgravity environment on the cellular cytoskeleton, cellular responses to extracellular signal molecules, morphology, events associated with cell division, and cellular physiology. Examples of studies in basic cell biology, as well as their potential importance to concerns for future enabling strategies, are presented.

The emergence of extracellular matrix mechanics and cell traction forces as important regulators of cellular self-organization.

PubMed

Checa, Sara; Rausch, Manuel K; Petersen, Ansgar; Kuhl, Ellen; Duda, Georg N

2015-01-01

Physical cues play a fundamental role in a wide range of biological processes, such as embryogenesis, wound healing, tumour invasion and connective tissue morphogenesis. Although it is well known that during these processes, cells continuously interact with the local extracellular matrix (ECM) through cell traction forces, the role of these mechanical interactions on large scale cellular and matrix organization remains largely unknown. In this study, we use a simple theoretical model to investigate cellular and matrix organization as a result of mechanical feedback signals between cells and the surrounding ECM. The model includes bi-directional coupling through cellular traction forces to deform the ECM and through matrix deformation to trigger cellular migration. In addition, we incorporate the mechanical contribution of matrix fibres and their reorganization by the cells. We show that a group of contractile cells will self-polarize at a large scale, even in homogeneous environments. In addition, our simulations mimic the experimentally observed alignment of cells in the direction of maximum stiffness and the building up of tension as a consequence of cell and fibre reorganization. Moreover, we demonstrate that cellular organization is tightly linked to the mechanical feedback loop between cells and matrix. Cells with a preference for stiff environments have a tendency to form chains, while cells with a tendency for soft environments tend to form clusters. The model presented here illustrates the potential of simple physical cues and their impact on cellular self-organization. It can be used in applications where cell-matrix interactions play a key role, such as in the design of tissue engineering scaffolds and to gain a basic understanding of pattern formation in organogenesis or tissue regeneration.

Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity

PubMed Central

Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest

2009-01-01

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

[Role of green tea in oxidative stress prevention].

PubMed

Metro, D; Muraca, U; Manasseri, L

2006-01-01

Oxidative stress is a condition caused by an increase of Reactive Oxygen Species (ROS) or by a shortage of the mechanisms of cellular protection and antioxidant defence. ROS have a potential oxidative effect towards various cellular macromolecules: proteins, nucleic acids, proteoglycans, lipids, with consequent damages in several cellular districts and promotion of the ageing process of the organism. However, some substances are able to prevent and/or reduce the damages caused by ROS; therefore, they are defined antioxidant. The present research studied, in a group of subjects, the antioxidant effects of the green tea, that was administered with fruit and vegetables in a strictly controlled diet. 50 subjects were selected and requested to daily consume 2-3 fruit portions (especially pineapple), 3-5 portions of vegetables (especially tomato) and 2-3 glasses of green tea for about 2 months to integrate the controlled basic diet. Some indicators of the oxidative stress were measured in the plasma before and after the integration period. The integration of a basic diet with supplements of fruit, vegetables and green tea turned out to be able in increasing both plasmatic total antioxidant capacity and endogenous antioxidant levels and to reduce the lipid peroxidation of the membranes, suggesting a reduction of the oxidative stress. These data suggest that an adequate supplement of antioxidants can prevent oxidative stress and correlated pathologies.

Zebrafish: an important tool for liver disease research.

PubMed

Goessling, Wolfram; Sadler, Kirsten C

2015-11-01

As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Emerging Biomimetic Applications of DNA Nanotechnology.

PubMed

Shen, Haijing; Wang, Yingqian; Wang, Jie; Li, Zhihao; Yuan, Quan

2018-06-25

Re-engineering cellular components and biological processes has received great interest and promised compelling advantages in applications ranging from basic cell biology to biomedicine. With the advent of DNA nanotechnology, the programmable self-assembly ability makes DNA an appealing candidate for rational design of artificial components with different structures and functions. This Forum Article summarizes recent developments of DNA nanotechnology in mimicking the structures and functions of existing cellular components. We highlight key successes in the achievements of DNA-based biomimetic membrane proteins and discuss the assembly behavior of these artificial proteins. Then, we focus on the construction of higher-order structures by DNA nanotechnology to recreate cell-like structures. Finally, we explore the current challenges and speculate on future directions of DNA nanotechnology in biomimetics.

Ultradian metronome: timekeeper for orchestration of cellular coherence.

PubMed

Lloyd, David; Murray, Douglas B

2005-07-01

Dynamic intracellular spatial and temporal organization emerges from spontaneous synchronization of a massive array of weakly coupled oscillators; the majority of subcellular processes are implicated in this integrated expression of cellular physiology. Evidence for this view comes mainly from studies of Saccharomyces cerevisiae growing in self-synchronized continuous cultures, in which a temperature-compensated ultradian clock (period of approximately 40 min) couples fermentation with redox state in addition to the transcriptome and cell-division-cycle progression. Functions for ultradian clocks have also been determined in other yeasts (e.g. Schizosaccharomyces pombe and Candida utilis), seven protists (e.g. Acanthamoeba castellanii and Paramecium tetraurelia), as well as cultured mammalian cells. We suggest that ultradian timekeeping is a basic universal necessity for coordinated intracellular coherence.

Feeding Behaviors in Cellular Slime Molds: A Microbial System To Study Competition.

ERIC Educational Resources Information Center

Bozzone, Donna M.

1997-01-01

Describes a laboratory project for first-year biology students that examines competition among various cellular slime molds. After a brief introduction to the topic of competition and basic life history information about cellular slime molds, students choose a question and design original experiments to seek an answer. (Author/AIM)

Quantum-dot cellular automata: Review and recent experiments (invited)

NASA Astrophysics Data System (ADS)

Snider, G. L.; Orlov, A. O.; Amlani, I.; Zuo, X.; Bernstein, G. H.; Lent, C. S.; Merz, J. L.; Porod, W.

1999-04-01

An introduction to the operation of quantum-dot cellular automata is presented, along with recent experimental results. Quantum-dot cellular automata (QCA) is a transistorless computation paradigm that addresses the issues of device density and interconnection. The basic building blocks of the QCA architecture, such as AND, OR, and NOT are presented. The experimental device is a four-dot QCA cell with two electrometers. The dots are metal islands, which are coupled by capacitors and tunnel junctions. An improved design of the cell is presented in which all four dots of the cell are coupled by tunnel junctions. The operation of this basic cell is confirmed by the externally controlled polarization change of the cell.

Single-Cell RNA Sequencing of Human T Cells.

PubMed

Villani, Alexandra-Chloé; Shekhar, Karthik

2017-01-01

Understanding how populations of human T cells leverage cellular heterogeneity, plasticity, and diversity to achieve a wide range of functional flexibility, particularly during dynamic processes such as development, differentiation, and antigenic response, is a core challenge that is well suited for single-cell analysis. Hypothesis-free evaluation of cellular states and subpopulations by transcriptional profiling of single T cells can identify relationships that may be obscured by targeted approaches such as FACS sorting on cell-surface antigens, or bulk expression analysis. While this approach is relevant to all cell types, it is of particular interest in the study of T cells for which classical phenotypic criteria are now viewed as insufficient for distinguishing different T cell subtypes and transitional states, and defining the changes associated with dysfunctional T cell states in autoimmunity and tumor-related exhaustion. This unit describes a protocol to generate single-cell transcriptomic libraries of human blood CD4 + and CD8 + T cells, and also introduces the basic bioinformatic steps to process the resulting sequence data for further computational analysis. We show how cellular subpopulations can be identified from transcriptional data, and derive characteristic gene expression signatures that distinguish these states. We believe single-cell RNA-seq is a powerful technique to study the cellular heterogeneity in complex tissues, a paradigm that will be of great value for the immune system.

A Range Finding Protocol to Support Design for Transcriptomics Experimentation: Examples of In-Vitro and In-Vivo Murine UV Exposure

PubMed Central

van Oostrom, Conny T.; Jonker, Martijs J.; de Jong, Mark; Dekker, Rob J.; Rauwerda, Han; Ensink, Wim A.; de Vries, Annemieke; Breit, Timo M.

2014-01-01

In transcriptomics research, design for experimentation by carefully considering biological, technological, practical and statistical aspects is very important, because the experimental design space is essentially limitless. Usually, the ranges of variable biological parameters of the design space are based on common practices and in turn on phenotypic endpoints. However, specific sub-cellular processes might only be partially reflected by phenotypic endpoints or outside the associated parameter range. Here, we provide a generic protocol for range finding in design for transcriptomics experimentation based on small-scale gene-expression experiments to help in the search for the right location in the design space by analyzing the activity of already known genes of relevant molecular mechanisms. Two examples illustrate the applicability: in-vitro UV-C exposure of mouse embryonic fibroblasts and in-vivo UV-B exposure of mouse skin. Our pragmatic approach is based on: framing a specific biological question and associated gene-set, performing a wide-ranged experiment without replication, eliminating potentially non-relevant genes, and determining the experimental ‘sweet spot’ by gene-set enrichment plus dose-response correlation analysis. Examination of many cellular processes that are related to UV response, such as DNA repair and cell-cycle arrest, revealed that basically each cellular (sub-) process is active at its own specific spot(s) in the experimental design space. Hence, the use of range finding, based on an affordable protocol like this, enables researchers to conveniently identify the ‘sweet spot’ for their cellular process of interest in an experimental design space and might have far-reaching implications for experimental standardization. PMID:24823911

Homocysteine and disease: Causal associations or epiphenomenons?

PubMed

Hannibal, Luciana; Blom, Henk J

2017-02-01

Nutritional and genetic deficiencies of folate and vitamin B 12 lead to elevation of cellular homocysteine (Hcy), which translates in increased plasma Hcy. The sources and role of elevated plasma Hcy in pathology continues to be a subject of intense scientific debate. Whether a cause, mediator or marker, little is known about the molecular mechanisms and interactions of Hcy with cellular processes that lead to disease. The use of folic acid reduces the incidence of neural tube defects, but the effect of Hcy-lowering interventions with folic acid in cardiovascular disease and cognitive impairment remains controversial. The fact that levels of Hcy in plasma do not always reflect cellular status of this amino acid may account for the substantial gaps that exist between epidemiological, intervention and basic research studies. Understanding whether plasma Hcy is a mechanistic player or an epiphenomenon in pathogenesis requires further investigation, and this research is essential to improve the assessment and potential treatment of hyperhomocysteinemias. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ciona as a Simple Chordate Model for Heart Development and Regeneration

PubMed Central

Evans Anderson, Heather; Christiaen, Lionel

2016-01-01

Cardiac cell specification and the genetic determinants that govern this process are highly conserved among Chordates. Recent studies have established the importance of evolutionarily-conserved mechanisms in the study of congenital heart defects and disease, as well as cardiac regeneration. As a basal Chordate, the Ciona model system presents a simple scaffold that recapitulates the basic blueprint of cardiac development in Chordates. Here we will focus on the development and cellular structure of the heart of the ascidian Ciona as compared to other Chordates, principally vertebrates. Comparison of the Ciona model system to heart development in other Chordates presents great potential for dissecting the genetic mechanisms that underlie congenital heart defects and disease at the cellular level and might provide additional insight into potential pathways for therapeutic cardiac regeneration. PMID:27642586

Cellular and chemical neuroscience of mammalian sleep.

PubMed

Datta, Subimal

2010-05-01

Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. Copyright 2010 Elsevier B.V. All rights reserved.

Olfactory epithelium: Cells, clinical disorders, and insights from an adult stem cell niche

PubMed Central

Choi, Rhea

2018-01-01

Disorders causing a loss of the sense of smell remain a therapeutic challenge. Basic research has, however, greatly expanded our knowledge of the organization and function of the olfactory system. This review describes advances in our understanding of the cellular components of the peripheral olfactory system, specifically the olfactory epithelium in the nose. The article discusses recent findings regarding the mechanisms involved in regeneration and cellular renewal from basal stem cells in the adult olfactory epithelium, considering the strategies involved in embryonic olfactory development and insights from research on other stem cell niches. In the context of clinical conditions causing anosmia, the current view of adult olfactory neurogenesis, tissue homeostasis, and failures in these processes is considered, along with current and future treatment strategies. Level of Evidence NA PMID:29492466

Roles and regulations of the ETS transcription factor ELF4/MEF

PubMed Central

Suico, Mary Ann; Shuto, Tsuyoshi; Kai, Hirofumi

2017-01-01

Abstract Most E26 transformation-specific (ETS) transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-like factor (ELF) subfamily of the ETS transcription factor family—myeloid elf-1-like factor (MEF), designated as ELF4—has been shown to be critically involved in immune response and signalling, osteogenesis, adipogenesis, cancer, and stem cell quiescence. ELF4 carries out these functions as a transcriptional activator or through interactions with its partner proteins. Mutations in ELF4 cause aberrant interactions and induce downstream processes that may lead to diseased cells. Knowing how ELF4 impinges on certain cellular processes and how it is regulated in the cells can lead to a better understanding of the physiological and pathological consequences of modulated ELF4 activity. PMID:27932483

The epithelial-mesenchymal interactions: insights into physiological and pathological aspects of oral tissues.

PubMed

Santosh, Arvind Babu Rajendra; Jones, Thaon Jon

2014-03-17

In the human biological system, the individual cells divide and form tissues and organs. These tissues are hetero-cellular. Basically any tissue consists of an epithelium and the connective tissue. The latter contains mainly mesenchymally-derived tissues with a diversified cell population. The cell continues to grow and differentiate in a pre-programmed manner using a messenger system. The epithelium and the mesenchymal portion of each tissue have two different origins and perform specific functions, but there is a well-defined interaction mechanism, which mediates between them. Epithelial mesenchymal interactions (EMIs) are part of this mechanism, which can be regarded as a biological conversation between epithelial and mesenchymal cell populations involved in the cellular differentiation of one or both cell populations. EMIs represent a process that is essential for cell growth, cell differentiation and cell multiplication. EMIs are associated with normal physiological processes in the oral cavity, such as odontogenesis, dentino-enamel junction formation, salivary gland development, palatogenesis, and also pathological processes, such as oral cancer. This paper focuses the role EMIs in odontogenesis, salivary gland development, palatogenesis and oral cancer.

Mechanistic systems modeling to guide drug discovery and development

PubMed Central

Schmidt, Brian J.; Papin, Jason A.; Musante, Cynthia J.

2013-01-01

A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. PMID:22999913

Mechanistic systems modeling to guide drug discovery and development.

PubMed

Schmidt, Brian J; Papin, Jason A; Musante, Cynthia J

2013-02-01

A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. Copyright © 2012 Elsevier Ltd. All rights reserved.

The German ISS-Experiment Cellular Responses to Radiation in Space (CERASP): The Effects of Single and Combined Space Flight Conditions on Mammalian Cells

NASA Astrophysics Data System (ADS)

Baumstark-Khan, C.; Hellweg, C. E.; Arenz, A.

The combined action of ionizing radiation and microgravity will continue to influence future space missions with special risks for astronauts on the Moon surface or for long duration missions to Mars Previous space flight experiments have reported additive neither sensitization nor protection as well as synergistic increased radiation effect under microgravity interactions of radiation and microgravity in different cell systems Although a direct effect of microgravity on enzymatic mechanisms can be excluded on thermo dynamical reasons modifications of cellular repair can not be excluded as such processes are under the control of cellular signal transduction systems which are controlled by environmental parameters presumably also by gravity DNA repair studies in space on bacteria yeast cells and human fibroblasts which were irradiated before flight gave contradictory results from inhibition of repair by microgravity to enhancement whereas others did not detect any influence of microgravity on repair At the Radiation Biology Department of the German Aerospace Center DLR recombinant bacterial and mammalian cell systems were developed as reporters for cellular signal transduction modulation by genotoxic environmental conditions The space experiment CERASP Cellular Responses to Radiation in Space to be performed at the International Space Station ISS will make use of such reporter cell lines thereby supplying basic information on the cellular response to radiation applied in microgravity One of the biological endpoints will be survival

Translating Research into Clinical Scale Manufacturing of Mesenchymal Stromal Cells

PubMed Central

Bieback, Karen; Kinzebach, Sven; Karagianni, Marianna

2010-01-01

It sounds simple to obtain sufficient numbers of cells derived from fetal or adult human tissues, isolate and/or expand the stem cells, and then transplant an appropriate number of these cells into the patient at the correct location. However, translating basic research into routine therapies is a complex multistep process which necessitates product regulation. The challenge relates to managing the expected therapeutic benefits with the potential risks and to balance the fast move to clinical trials with time-consuming cautious risk assessment. This paper will focus on the definition of mesenchymal stromal cells (MSCs), and challenges and achievements in the manufacturing process enabling their use in clinical studies. It will allude to different cellular sources, special capacities of MSCs, but also to current regulations, with a special focus on accessory material of human or animal origin, like media supplements. As cellular integrity and purity, formulation and lot release testing of the final product, validation of all procedures, and quality assurance are of utmost necessity, these topics will be addressed. PMID:21318154

A nonstandard finite difference scheme for a basic model of cellular immune response to viral infection

NASA Astrophysics Data System (ADS)

Korpusik, Adam

2017-02-01

We present a nonstandard finite difference scheme for a basic model of cellular immune response to viral infection. The main advantage of this approach is that it preserves the essential qualitative features of the original continuous model (non-negativity and boundedness of the solution, equilibria and their stability conditions), while being easy to implement. All of the qualitative features are preserved independently of the chosen step-size. Numerical simulations of our approach and comparison with other conventional simulation methods are presented.

Basic and applied research program. Semiannual report, July-December 1978

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butler, B.L.

1979-12-01

The status of research projects in the Basic and Applied Research Program at SERI is presented for the semiannual period ending December 31, 1978. The five tasks in this program are grouped into Materials Research and Development, Materials Processing and Development, Photoconversion Research, Exploratory Research, and Energy Resource and Assessment and have been carried out by personnel in the Materials, Bio/Chemical Conversion, and Energy Resource and Assessment Branches. Subtask elements in the task areas include coatings and films, polymers, metallurgy and corrosion, optical materials, surfaces and interfaces in materials research and development; photochemistry, photoelectrochemistry, and photobiology in photoconversion; thin glassmore » mirror development, silver degradation of mirrors, hail resistance of thin glass, thin glass manufacturing, cellular glass development, and sorption by desiccants in materials processing and development; and thermoelectric energy conversion, desiccant cooling, photothermal degradation, and amorphous materials in exploratory research. For each task or subtask element, the overview, scope, goals, approach, apparatus and equipment, and supporting subcontracts are presented, as applicable, in addition to the status of the projects in each task or subtask. Listing of publications and reports authored by personnel associated with the Basic and Applied Research Program and prepared or published during 1978 are also included.« less

[Learning and implicit memory: mechanisms and neuroplasticity].

PubMed

Machado, S; Portella, C E; Silva, J G; Velasques, B; Bastos, V H; Cunha, M; Basile, L; Cagy, M; Piedade, R A; Ribeiro, P

Learning and memory are complex processes that researchers have been attempting to unravel for over a century in order to gain a clear view of the underlying mechanisms. To review the basic cellular and molecular mechanisms involved in the process of procedural retention, to offer an overall view of the fundamental mechanisms involved in storing information by means of theories and models of memory, and to discuss the different types of memory and the role played by the cerebellum as a modulator of procedural memory. Experimental results from recent decades have opened up new areas of study regarding the participation of the biochemical and cellular processes related to the consolidation of information in the nervous system. The neuronal circuits involved in acquiring and consolidating memory are still not fully understood and the exact location of memory in the nervous system remains unknown. A number of intrinsic and extrinsic factors interfere in these processes, such as molecular (long-term potentiation and depression) and cellular mechanisms, which respond to communication and transmission between nerve cells. There are also factors that have their origin in the outside environment, which use the association of events to bring about the formation of new memories or may divert the subject from his or her main focus. Memory is not a singular occurrence; it is sub-divided into declarative and non-declarative or, when talking about the time it lasts, into short and long-term memory. Moreover, given its relation with neuronal mechanisms of learning, memory cannot be said to constitute an isolated process.

Neuroimmunology of disordered sleep in depression and alcoholism.

PubMed

Irwin, M

2001-11-01

The specific functions of sleep are not known, although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed and alcoholic subjects correlates with declines in natural and cellular immunity and is associated with alterations in the complex cytokine network. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the physiological significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep.

75 FR 26970 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

...-496-8551, [email protected] . Name of Committee: Molecular, Cellular and Developmental...: Oncology 1--Basic Translational Integrated Review Group, Cancer Genetics Study Section. Date: June 3-4... 20892, (301) 435-1154, [email protected] . Name of Committee: Molecular, Cellular and Developmental...

75 FR 25273 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-07

... Genetics Integrated Review Group, Molecular Genetics C Study Section. Date: June 3-4, 2010. Time: 8 a.m. to... Committee: Oncology 1-Basic Translational Integrated Review Group, Cancer Molecular Pathobiology Study... Committee: Molecular, Cellular and Developmental Neuroscience Integrated Review Group, Cellular and...

A Real Space Cellular Automaton Laboratory

NASA Astrophysics Data System (ADS)

Rozier, O.; Narteau, C.

2013-12-01

Investigations in geomorphology may benefit from computer modelling approaches that rely entirely on self-organization principles. In the vast majority of numerical models, instead, points in space are characterised by a variety of physical variables (e.g. sediment transport rate, velocity, temperature) recalculated over time according to some predetermined set of laws. However, there is not always a satisfactory theoretical framework from which we can quantify the overall dynamics of the system. For these reasons, we prefer to concentrate on interaction patterns using a basic cellular automaton modelling framework, the Real Space Cellular Automaton Laboratory (ReSCAL), a powerful and versatile generator of 3D stochastic models. The objective of this software suite released under a GNU license is to develop interdisciplinary research collaboration to investigate the dynamics of complex systems. The models in ReSCAL are essentially constructed from a small number of discrete states distributed on a cellular grid. An elementary cell is a real-space representation of the physical environment and pairs of nearest neighbour cells are called doublets. Each individual physical process is associated with a set of doublet transitions and characteristic transition rates. Using a modular approach, we can simulate and combine a wide range of physical, chemical and/or anthropological processes. Here, we present different ingredients of ReSCAL leading to applications in geomorphology: dune morphodynamics and landscape evolution. We also discuss how ReSCAL can be applied and developed across many disciplines in natural and human sciences.

Molecular genetic approaches to the study of cellular senescence.

PubMed

Goletz, T J; Smith, J R; Pereira-Smith, O M

1994-01-01

Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular traditional Chinese medicine on photobiomodulation

NASA Astrophysics Data System (ADS)

Liu, Timon Cheng-Yi; Cheng, Lei; Liu, Jiang; Wang, Shuang-Xi; Xu, Xiao-Yang; Deng, Xiao-Yuan; Liu, Song-Hao

2006-09-01

Although yin-yang is one of the basic models of traditional Chinese medicine (TCM) for TCM objects such as whole body, five zangs or six fus, they are widely used to discuss cellular processes in papers of famous journals such as Cell, Nature, or Science. In this paper, the concept of the degree of difficulty (DD) of a process was introduced to redefine yin and yang and extend the TCM yin-yang model to the DD yin-yang model so that we have the DD yin-yang inter-transformation, the DD yin-yang antagonism, the DD yin-yang interdependence and the DD yin ping yang mi, which and photobiomodulation (PBM) on cells are supported by each other. It was shown that healthy cells are in the DD yin ping yang mi so that there is no PBM, and there is PBM on non-healthy cells until the cells become healthy so that PBM can be called a cellular rehabilitation. The DD yin-yang inter-transformation holds for our biological information model of PBM. The DD yin-yang antagonism and the DD yin-yang interdependence also hold for a series of experimental studies such as the stimulation of DNA synthesis in HeLa cells after simultaneous irradiation with narrow-band red light and a wide-band cold light, or consecutive irradiation with blue and red light.

Thin film bioreactors in space

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.; Scheld, H. W.

1989-01-01

Studies from the Skylab, SL-3 and D-1 missions have demonstrated that biological organisms grown in microgravity have changes in basic cellular functions such as DNA, mRNA and protein synthesis, cytoskeleton synthesis, glucose utilization, and cellular differentiation. Since microgravity could affect prokaryotic and eukaryotic cells at a subcellular and molecular level, space offers an opportunity to learn more about basic biological systems with one inmportant variable removed. The thin film bioreactor will facilitate the handling of fluids in microgravity, under constant temperature and will allow multiple samples of cells to be grown with variable conditions. Studies on cell cultures grown in microgravity would make it possible to identify and quantify changes in basic biological function in microgravity which are needed to develop new applications of orbital research and future biotechnology.

Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics

PubMed Central

Lin, Sabrina C.; Bays, Brett C.; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

2016-01-01

There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells. PMID:26848582

Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics.

PubMed

Zahedi, Atena; On, Vincent; Lin, Sabrina C; Bays, Brett C; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

2016-01-01

There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells.

Administrative and research policies required to bring cellular therapies from the research laboratory to the patient's bedside.

PubMed

Yim, Robyn

2005-10-01

The research process is a balance between the inherent risks of new discoveries and the risks of research participant safety. Conflicts of interest, inherent to the research process, as well as those introduced by emerging cellular therapies, have the potential to compromise safety. The relationship of trust between the researcher and the clinical trial participant facilitates objective decision making, in the best interest of both parties. In the setup of each clinical trial, investigators incorporate ethical, political, legal, financial, and regulatory considerations as protocols are established. Responsibility to abide by these decisions ensures a systematic process and safeguards participants in this process. The integrity of the research process is strengthened by identifying potential conflicting issues with the guiding principles established in the protocols, which may threaten the objectivity of involved parties and jeopardize safety of the participants. The rapid pace and changing paradigms of new discoveries in cellular therapies exaggerate existing conflicts and introduce new ones. Ethical issues raised by emerging cellular therapies include the division of opinions regarding the use of embryonic and fetal tissue to develop stem cell lines for research, the individual versus professional conscience of a researcher, overselling of outcomes as a result of the researcher's desire to be the first to discover a cellular therapy, and therapeutic misconception resulting from a participant's desire for a miracle cure. The basic ethical issue of whether stem cells should be utilized as a cellular therapy raises heated debates because some believe that it is not acceptable to use fetal material as a source of research material for future cures and others feel equally as strong that inaction is unethical because it results in needless suffering and death owing to the absence of this research. Political issues include the divergent position statements of presidential administrations on cellular therapy, variations in individual state laws, and states becoming involved in research funding, such as California's Proposition 71. Legal concerns include expanding private litigation with diversity of lawsuits, expanding lists of defendants, and the use of class-action lawsuits in research cases. Ownership issues also arise in terms of intellectual property, patents, and ownership of stem cells collected from minors, as in umbilical cord blood donations. Situations that challenge the regulatory processes established to ensure participant safety include differences in reporting requirements for private- and public-funded research and the lack of adequate funding and resources to implement and support the institutional review board (IRB) process. Financial considerations influence the development of clinical protocols, because funding is often limited. Financial incentives, personal investment in companies funding research activities, and fundraising pressures may present potential conflicts. In addition, the increasing role of emerging biotechnology start-up companies and pharmaceutical companies in clinical research introduces additional financial considerations. Administrative policies are needed to address these possible conflicts and ensure research participant safety as cellular therapies progress from the research laboratories to the patient's bedside. Administrative policies to ensure minimum standards of quality for emerging products before human clinical trials, policies to enforce consistent reporting requirements for private and public cellular research, policies to minimize financial conflicts of interest, policies to strengthen implementation of the existing IRB process and to structure into the process a consistent, systematic review of these identified conflicts, and policies to limit private litigation will help to preserve the objectivity of the review process and ultimately increase participant safety.

Language learning impairments: integrating basic science, technology, and remediation.

PubMed

Tallal, P; Merzenich, M M; Miller, S; Jenkins, W

1998-11-01

One of the fundamental goals of the modern field of neuroscience is to understand how neuronal activity gives rise to higher cortical function. However, to bridge the gap between neurobiology and behavior, we must understand higher cortical functions at the behavioral level at least as well as we have come to understand neurobiological processes at the cellular and molecular levels. This is certainly the case in the study of speech processing, where critical studies of behavioral dysfunction have provided key insights into the basic neurobiological mechanisms relevant to speech perception and production. Much of this progress derives from a detailed analysis of the sensory, perceptual, cognitive, and motor abilities of children who fail to acquire speech, language, and reading skills normally within the context of otherwise normal development. Current research now shows that a dysfunction in normal phonological processing, which is critical to the development of oral and written language, may derive, at least in part, from difficulties in perceiving and producing basic sensory-motor information in rapid succession--within tens of ms (see Tallal et al. 1993a for a review). There is now substantial evidence supporting the hypothesis that basic temporal integration processes play a fundamental role in establishing neural representations for the units of speech (phonemes), which must be segmented from the (continuous) speech stream and combined to form words, in order for the normal development of oral and written language to proceed. Results from magnetic resonance imaging (MRI) and positron emission tomography (PET) studies, as well as studies of behavioral performance in normal and language impaired children and adults, will be reviewed to support the view that the integration of rapidly changing successive acoustic events plays a primary role in phonological development and disorders. Finally, remediation studies based on this research, coupled with neuroplasticity research, will be presented.

Structure and function of yeast glutaredoxin 2 depend on postranslational processing and are related to subcellular distribution.

PubMed

Porras, Pablo; McDonagh, Brian; Pedrajas, Jose Rafael; Bárcena, J Antonio; Padilla, C Alicia

2010-04-01

We have previously shown that glutaredoxin 2 (Grx2) from Saccharomyces cerevisiae localizes at 3 different subcellular compartments, cytosol, mitochondrial matrix and outer membrane, as the result of different postranslational processing of one single gene. Having set the mechanism responsible for this remarkable phenomenon, we have now aimed at defining whether this diversity of subcellular localizations correlates with differences in structure and function of the Grx2 isoforms. We have determined the N-terminal sequence of the soluble mitochondrial matrix Grx2 by mass spectrometry and have determined the exact cleavage site by Mitochondrial Processing Peptidase (MPP). As a consequence of this cleavage, the mitochondrial matrix Grx2 isoform possesses a basic tetrapeptide extension at the N-terminus compared to the cytosolic form. A functional relationship to this structural difference is that mitochondrial Grx2 displays a markedly higher activity in the catalysis of GSSG reduction by the mitochondrial dithiol dihydrolipoamide. We have prepared Grx2 mutants affected on key residues inside the presequence to direct the protein to one single cellular compartment; either the cytosol, the mitochondrial membrane or the matrix and have analyzed their functional phenotypes. Strains expressing Grx2 only in the cytosol are equally sensitive to H(2)O(2) as strains lacking the gene, whereas those expressing Grx2 exclusively in the mitochondrial matrix are more resistant. Mutations on key basic residues drastically affect the cellular fate of the protein, showing that evolutionary diversification of Grx2 structural and functional properties are strictly dependent on the sequence of the targeting signal peptide. Copyright 2009 Elsevier B.V. All rights reserved.

Seth M. Noone | NREL

Science.gov Websites

Education M.S., Biomedical Basic Science, Department of Biochemistry and Molecular Genetics, University of Interaction with Histones H3 and H4," Molecular and Cellular Biology (2013) "The Lysine 48 and Cerevisiae," Molecular and Cellular Biology (2007) View all NREL Publications for Seth M. Noone

Evolutionary tradeoffs in cellular composition across diverse bacteria

PubMed Central

Kempes, Christopher P; Wang, Lawrence; Amend, Jan P; Doyle, John; Hoehler, Tori

2016-01-01

One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species. Here we provide a comprehensive analysis of how cellular composition changes across the diversity of bacteria as connected with physiological function and metabolism, spanning five orders of magnitude in body size. We present an analysis of the trends with cell volume that covers shifts in genomic, protein, cellular envelope, RNA and ribosomal content. We show that trends in protein content are more complex than a simple proportionality with the overall genome size, and that the number of ribosomes is simply explained by cross-species shifts in biosynthesis requirements. Furthermore, we show that the largest and smallest bacteria are limited by physical space requirements. At the lower end of size, cell volume is dominated by DNA and protein content—the requirement for which predicts a lower limit on cell size that is in good agreement with the smallest observed bacteria. At the upper end of bacterial size, we have identified a point at which the number of ribosomes required for biosynthesis exceeds available cell volume. Between these limits we are able to discuss systematic and dramatic shifts in cellular composition. Much of our analysis is connected with the basic energetics of cells where we show that the scaling of metabolic rate is surprisingly superlinear with all cellular components. PMID:27046336

Self-organized Motion During Dictyostelium amoebae aggregation

NASA Astrophysics Data System (ADS)

Levine, Herbert

2004-03-01

After starvation, amoeba of the cellular slime mold Dictyostelium discoideum aggregate to form rudimentary multicellular organisms. The coordination of the individual motions of hundreds of thousands of individual cells is an important ingredient in the success of this process. This coordination is accomplished by chemical signaling during the early stages and by direct cell-cell interactions once the cells reach the nascent mound. This talk will review the basic nonequilibrium physics underlying the spatial patterns formed by these cooperative motions, including high-density incoming streams and spontaneously rotating mounds.

Redox signaling: Potential arbitrator of autophagy and apoptosis in therapeutic response.

PubMed

Zhang, Lu; Wang, Kui; Lei, Yunlong; Li, Qifu; Nice, Edouard Collins; Huang, Canhua

2015-12-01

Redox signaling plays important roles in the regulation of cell death and survival in response to cancer therapy. Autophagy and apoptosis are discrete cellular processes mediated by distinct groups of regulatory and executioner molecules, and both are thought to be cellular responses to various stress conditions including oxidative stress, therefore controlling cell fate. Basic levels of reactive oxygen species (ROS) may function as signals to promote cell proliferation and survival, whereas increase of ROS can induce autophagy and apoptosis by damaging cellular components. Growing evidence in recent years argues for ROS that below detrimental levels acting as intracellular signal transducers that regulate autophagy and apoptosis. ROS-regulated autophagy and apoptosis can cross-talk with each other. However, how redox signaling determines different cell fates by regulating autophagy and apoptosis remains unclear. In this review, we will focus on understanding the delicate molecular mechanism by which autophagy and apoptosis are finely orchestrated by redox signaling and discuss how this understanding can be used to develop strategies for the treatment of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Mechanics and morphogenesis of fission yeast cells.

PubMed

Davì, Valeria; Minc, Nicolas

2015-12-01

The integration of biochemical and biomechanical elements is at the heart of morphogenesis. While animal cells are relatively soft objects which shape and mechanics is mostly regulated by cytoskeletal networks, walled cells including those of plants, fungi and bacteria are encased in a rigid cell wall which resist high internal turgor pressure. How these particular mechanical properties may influence basic cellular processes, such as growth, shape and division remains poorly understood. Recent work using the model fungal cell fission yeast, Schizosaccharomyces pombe, highlights important contribution of cell mechanics to various morphogenesis processes. We envision this genetically tractable system to serve as a novel standard for the mechanobiology of walled cell. Copyright © 2015 Elsevier Ltd. All rights reserved.

Constraints on Fluctuations in Sparsely Characterized Biological Systems.

PubMed

Hilfinger, Andreas; Norman, Thomas M; Vinnicombe, Glenn; Paulsson, Johan

2016-02-05

Biochemical processes are inherently stochastic, creating molecular fluctuations in otherwise identical cells. Such "noise" is widespread but has proven difficult to analyze because most systems are sparsely characterized at the single cell level and because nonlinear stochastic models are analytically intractable. Here, we exactly relate average abundances, lifetimes, step sizes, and covariances for any pair of components in complex stochastic reaction systems even when the dynamics of other components are left unspecified. Using basic mathematical inequalities, we then establish bounds for whole classes of systems. These bounds highlight fundamental trade-offs that show how efficient assembly processes must invariably exhibit large fluctuations in subunit levels and how eliminating fluctuations in one cellular component requires creating heterogeneity in another.

Modelling the morphology of migrating bacterial colonies

NASA Astrophysics Data System (ADS)

Nishiyama, A.; Tokihiro, T.; Badoual, M.; Grammaticos, B.

2010-08-01

We present a model which aims at describing the morphology of colonies of Proteus mirabilis and Bacillus subtilis. Our model is based on a cellular automaton which is obtained by the adequate discretisation of a diffusion-like equation, describing the migration of the bacteria, to which we have added rules simulating the consolidation process. Our basic assumption, following the findings of the group of Chuo University, is that the migration and consolidation processes are controlled by the local density of the bacteria. We show that it is possible within our model to reproduce the morphological diagrams of both bacteria species. Moreover, we model some detailed experiments done by the Chuo University group, obtaining a fine agreement.

Constraints on Fluctuations in Sparsely Characterized Biological Systems

NASA Astrophysics Data System (ADS)

Hilfinger, Andreas; Norman, Thomas M.; Vinnicombe, Glenn; Paulsson, Johan

2016-02-01

Biochemical processes are inherently stochastic, creating molecular fluctuations in otherwise identical cells. Such "noise" is widespread but has proven difficult to analyze because most systems are sparsely characterized at the single cell level and because nonlinear stochastic models are analytically intractable. Here, we exactly relate average abundances, lifetimes, step sizes, and covariances for any pair of components in complex stochastic reaction systems even when the dynamics of other components are left unspecified. Using basic mathematical inequalities, we then establish bounds for whole classes of systems. These bounds highlight fundamental trade-offs that show how efficient assembly processes must invariably exhibit large fluctuations in subunit levels and how eliminating fluctuations in one cellular component requires creating heterogeneity in another.

Skin aging and menopause : implications for treatment.

PubMed

Raine-Fenning, Nicholas J; Brincat, Mark P; Muscat-Baron, Yves

2003-01-01

The skin is one of the largest organs of the body, which is significantly affected by the aging process and menopause. The significant changes sustained by the skin during the menopause are due to the effect sustained on the skin's individual components. The estrogen receptor has been detected on the cellular components of the skin. Accordingly, dermal cellular metabolism is influenced by the hypoestrogenoemic state of menopause leading to changes in the collagen content, alterations in the concentration of glycoaminoglycans and most importantly the water content. Consequently changes in these basic components leads to an alteration in function compatible with skin aging. Changes in the skin collagen leads to diminished elasticity and skin strength. Collagen content may be measured by various methods such as direct skin biopsy, skin blister assessment for collagen markers and skin thickness measurement. All these variables indicate a reduction in collagen content following menopause. This may be reversed with the administration of estrogen given both topically and systemically.A reduction in hydrophilic glycoaminglycans leads to a direct reduction in water content, which influences the skin turgor. These effects on glycoaminoglycans, due to the hypoestrogenia, have been clearly shown in animal studies and appeared to be rapidly reversed with the application of estrogens. The sum total of these basic effects on the skin leads to wrinkles, the skin condition typifying skin aging.Structures resident in the skin are likewise influenced by menopause. Changes to the cutaneous vascular reactivity are noted following menopause. Capillary blood flow velocity decreases significantly in postmenopausal women. Postmenopausal flushing is due to profound vasodilatation in the dermal papillae. Hair growth is also influenced by the hormonal milieu and consequently hair loss has been associated with the beginning of menopause. Treatments administered for menopause, in particular hormone replacement therapy, appear to alter its effects on the basic components of the skin as well as the more complex structures residing in the skin, consequently retarding the skin aging process.

The Vertebrate Brain, Evidence of Its Modular Organization and Operating System: Insights into the Brain's Basic Units of Structure, Function, and Operation and How They Influence Neuronal Signaling and Behavior.

PubMed

Baslow, Morris H

2011-01-01

The human brain is a complex organ made up of neurons and several other cell types, and whose role is processing information for use in eliciting behaviors. However, the composition of its repeating cellular units for both structure and function are unresolved. Based on recent descriptions of the brain's physiological "operating system", a function of the tri-cellular metabolism of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy, and on the nature of "neuronal words and languages" for intercellular communication, insights into the brain's modular structural and functional units have been gained. In this article, it is proposed that the basic structural unit in brain is defined by its physiological operating system, and that it consists of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular system endothelial cells. It is also proposed that the basic functional unit in the brain is defined by how neurons communicate, and consists of two neurons and their interconnecting dendritic-synaptic-dendritic field. Since a functional unit is composed of two neurons, it requires two structural units to form a functional unit. Thus, the brain can be envisioned as being made up of the three-dimensional stacking and intertwining of myriad structural units which results not only in its gross structure, but also in producing a uniform distribution of binary functional units. Since the physiological NAA-NAAG operating system for supply of energy is repeated in every structural unit, it is positioned to control global brain function.

TFEB at a glance.

PubMed

Napolitano, Gennaro; Ballabio, Andrea

2016-07-01

The transcription factor EB (TFEB) plays a pivotal role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation, which occurs at the lysosomal surface. Phosphorylated TFEB is retained in the cytoplasm, whereas dephosphorylated TFEB translocates to the nucleus to induce the transcription of target genes. Thus, a lysosome-to-nucleus signaling pathway regulates cellular energy metabolism through TFEB. Recently, in vivo studies have revealed that TFEB is also involved in physiological processes, such as lipid catabolism. TFEB has attracted a lot of attention owing to its ability to induce the intracellular clearance of pathogenic factors in a variety of murine models of disease, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity. In this Cell Science at a Glance article and accompanying poster, we present an overview of the latest research on TFEB function and its implication in human diseases. © 2016. Published by The Company of Biologists Ltd.

In silico evidence for sequence-dependent nucleosome sliding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lequieu, Joshua; Schwartz, David C.; de Pablo, Juan J.

Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nudeosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces andmore » the corresponding dynamics of nudeosome repositioning. The mechanism of nudeosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.« less

Studying Catabolism of Protein ADP-Ribosylation.

PubMed

Palazzo, Luca; James, Dominic I; Waddell, Ian D; Ahel, Ivan

2017-01-01

Protein ADP-ribosylation is a conserved posttranslational modification that regulates many major cellular functions, such as DNA repair, transcription, translation, signal transduction, stress response, cell division, aging, and cell death. Protein ADP-ribosyl transferases catalyze the transfer of an ADP-ribose (ADPr) group from the β-nicotinamide adenine dinucleotide (β-NAD + ) cofactor onto a specific target protein with the subsequent release of nicotinamide. ADP-ribosylation leads to changes in protein structure, function, stability, and localization, thus defining the appropriate cellular response. Signaling processes that are mediated by modifications need to be finely tuned and eventually silenced and one of the ways to achieve this is through the action of enzymes that remove (reverse) protein ADP-ribosylation in a timely fashion such as PARG, TARG1, MACROD1, and MACROD2. Here, we describe several basic methods used to study the enzymatic activity of de-ADP-ribosylating enzymes.

Multi-classification of cell deformation based on object alignment and run length statistic.

PubMed

Li, Heng; Liu, Zhiwen; An, Xing; Shi, Yonggang

2014-01-01

Cellular morphology is widely applied in digital pathology and is essential for improving our understanding of the basic physiological processes of organisms. One of the main issues of application is to develop efficient methods for cell deformation measurement. We propose an innovative indirect approach to analyze dynamic cell morphology in image sequences. The proposed approach considers both the cellular shape change and cytoplasm variation, and takes each frame in the image sequence into account. The cell deformation is measured by the minimum energy function of object alignment, which is invariant to object pose. Then an indirect analysis strategy is employed to overcome the limitation of gradual deformation by run length statistic. We demonstrate the power of the proposed approach with one application: multi-classification of cell deformation. Experimental results show that the proposed method is sensitive to the morphology variation and performs better than standard shape representation methods.

Developmental consequences of cryopreservation of mammalian oocytes and embryos.

PubMed

Smith, Gary D; Silva E Silva, Cristine Ane

2004-08-01

During the last three decades, significant advances have been made in successful cryopreservation of mammalian preimplantation embryos, and more recently oocytes. The ability to cryopreserve, thaw, and establish pregnancies with supernumerary preimplantation embryos has become an important tool in fertility treatment. Human oocyte cryopreservation has practical application in preserving fertility for individuals at risk of compromised egg quality due to cancer treatments or advanced maternal age. While oocyte/embryo cryopreservation success has increased over time, there is still room for improvement. Oocytes and embryos are susceptible to cryo-damage, which collectively entails cellular damage caused by mechanical, chemical, or thermal forces during the freeze-thaw process. Basic studies focused on understanding cellular structures, their composition, and more importantly their functions, in normal cell developments will continue to be critical in assessing, understanding, and correcting oocyte/embryo cryo-damage. This review will delineate many of the oocyte/embryo intracellular and extracellular structures that are or may be compromised during cryopreservation. A global theme presented throughout this review is that many structural components of the oocyte/embryo also have essential functional roles in development. Compromising these cellular structures, and thus their cellular homeostatic functions, can deleteriously influence initial cryo-survival or compromise subsequent normal development through effects on the oocyte and/or early embryo.

Advances in the cellular and molecular biology of angiogenesis.

PubMed

Egginton, Stuart; Bicknell, Roy

2011-12-01

Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.

GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy.

PubMed

Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

2015-01-01

Stem cells, which can be derived from different sources, demonstrate promising therapeutic evidences for cellular therapies. Among various types of stem cell, mesenchymal stem cells are one of the most common stem cells that are used in cellular therapy. Human subcutaneous adipose tissue provides an easy accessible source of mesenchymal stem cells with some considerable advantages. Accordingly, various preclinical and clinical investigations have shown enormous potential of adipose-derived stromal cells in regenerative medicine. Consequently, increasing clinical applications of these cells has elucidated the importance of safety concerns regarding clinical transplantation. Therefore, clinical-grade preparation of adipose-derived stromal cells in accordance with current good manufacturing practice guidelines is an essential part of their clinical applications to ensure the safety, quality, characteristics, and identity of cell products. Additionally, GMP-compliant cell manufacturing involves several issues to provide a quality assurance system during translation from the basic stem cell sciences into clinical investigations and applications. On the other hand, advanced cellular therapy requires extensive validation, process control, and documentation. It also evidently elucidates the critical importance of production methods and probable risks. Therefore, implementation of a quality management and assurance system in accordance with GMP guidelines can greatly reduce these risks particularly in the higher-risk category or "more than minimally manipulated" products.

From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

PubMed

Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

2018-04-25

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

Integration of Basic Sciences in Health's Courses

ERIC Educational Resources Information Center

Azzalis, L. A.; Giavarotti, L.; Sato, S. N.; Barros, N. M. T.; Junqueira, V. B. C.; Fonseca, F. L. A.

2012-01-01

Concepts from disciplines such as Biochemistry, Genetics, Cellular and Molecular Biology are essential to the understanding and treatment of an elevated number of illnesses, but often they are studied separately, with no integration between them. This article proposes a model for basic sciences integration based on problem-based learning (PBL) and…

Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

PubMed Central

2015-01-01

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity. PMID:25546652

Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq.

PubMed

Marchal, Claire; Sasaki, Takayo; Vera, Daniel; Wilson, Korey; Sima, Jiao; Rivera-Mulia, Juan Carlos; Trevilla-García, Claudia; Nogues, Coralin; Nafie, Ebtesam; Gilbert, David M

2018-05-01

This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.

The Dictyostelium discoideum RACK1 orthologue has roles in growth and development

PubMed Central

2014-01-01

Background The receptor for activated C-kinase 1 (RACK1) is a conserved protein belonging to the WD40 repeat family of proteins. It folds into a beta propeller with seven blades which allow interactions with many proteins. Thus it can serve as a scaffolding protein and have roles in several cellular processes. Results We identified the product of the Dictyostelium discoideum gpbB gene as the Dictyostelium RACK1 homolog. The protein is mainly cytosolic but can also associate with cellular membranes. DdRACK1 binds to phosphoinositides (PIPs) in protein-lipid overlay and liposome-binding assays. The basis of this activity resides in a basic region located in the extended loop between blades 6 and 7 as revealed by mutational analysis. Similar to RACK1 proteins from other organisms DdRACK1 interacts with G protein subunits alpha, beta and gamma as shown by yeast two-hybrid, pulldown, and immunoprecipitation assays. Unlike the Saccharomyces cerevisiae and Cryptococcus neoformans RACK1 proteins it does not appear to take over Gβ function in D. discoideum as developmental and other defects were not rescued in Gβ null mutants overexpressing GFP-DdRACK1. Overexpression of GFP-tagged DdRACK1 and a mutant version (DdRACK1mut) which carried a charge-reversal mutation in the basic region in wild type cells led to changes during growth and development. Conclusion DdRACK1 interacts with heterotrimeric G proteins and can through these interactions impact on processes specifically regulated by these proteins. PMID:24930026

Towards a Quantum Game of Life

NASA Astrophysics Data System (ADS)

Flitney, Adrian P.; Abbott, Derek

Cellular automata provide a means of obtaining complex behaviour from a simple array of cells and a deterministic transition function. They supply a method of computation that dispenses with the need for manipulation of individual cells and they are computationally universal. Classical cellular automata have proved of great interest to computer scientists but the construction of quantum cellular automata pose particular difficulties. We present a version of John Conway's famous two-dimensional classical cellular automata Life that has some quantum-like features, including interference effects. Some basic structures in the new automata are given and comparisons are made with Conway's game.

Tip-enhanced Raman scattering of bacillus subtilis spores

NASA Astrophysics Data System (ADS)

Rusciano, G.; Zito, G.; Pesce, G.; Sasso, A.; Isticato, R.; Ricca, E.

2015-07-01

Understanding of the complex interactions of molecules at biological interfaces is a fundamental issue in biochemistry, biotechnology as well as biomedicine. A plethora of biological processes are ruled by the molecular texture of cellular membrane: cellular communications, drug transportations and cellular recognition are just a few examples of such chemically-mediated processes. Tip-Enhanced Raman Scattering (TERS) is a novel, Raman-based technique which is ideally suited for this purpose. TERS relies on the combination of scanning probe microscopy and Raman spectroscopy. The basic idea is the use of a metalled tip as a sort of optical nano-antenna, which gives place to SERS effect close to the tip end. Herein, we present the application of TERS to analyze the surface of Bacillus subtilis spores. The choice of this biological systems is related to the fact that a number of reasons support the use of spores as a mucosal delivery system. The remarkable and well-documented resistance of spores to various environmental and toxic effects make them clear potentials as a novel, surface-display system. Our experimental outcomes demonstrate that TERS is able to provide a nano-scale chemical imaging of spore surface. Moreover, we demonstrate that TERS allows differentiation between wilde-type spore and genetically modified strains. These results hold promise for the characterization and optimization of spore surface for drug-delivery applications.

A self-organized criticality model for ion temperature gradient mode driven turbulence in confined plasma

NASA Astrophysics Data System (ADS)

Isliker, H.; Pisokas, Th.; Strintzi, D.; Vlahos, L.

2010-08-01

A new self-organized criticality (SOC) model is introduced in the form of a cellular automaton (CA) for ion temperature gradient (ITG) mode driven turbulence in fusion plasmas. Main characteristics of the model are that it is constructed in terms of the actual physical variable, the ion temperature, and that the temporal evolution of the CA, which necessarily is in the form of rules, mimics actual physical processes as they are considered to be active in the system, i.e., a heating process and a local diffusive process that sets on if a threshold in the normalized ITG R /LT is exceeded. The model reaches the SOC state and yields ion temperature profiles of exponential shape, which exhibit very high stiffness, in that they basically are independent of the loading pattern applied. This implies that there is anomalous heat transport present in the system, despite the fact that diffusion at the local level is imposed to be of a normal kind. The distributions of the heat fluxes in the system and of the heat out-fluxes are of power-law shape. The basic properties of the model are in good qualitative agreement with experimental results.

Cellular Therapies Clinical Research Roadmap: lessons learned on how to move a cellular therapy into a clinical trial.

PubMed

Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M

2015-04-01

A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, by means of an Investigational New Drug (IND) application, into early-phase clinical trials. The roadmap describes four key areas: basic and preclinical research, resource development, translational research and Good Manufacturing Practice (GMP) and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value with the use of a model of the relevant disease. During resource development, the appropriate specialists and the required expertise to bring this product into the clinic are identified (eg, researchers, regulatory specialists, GMP manufacturing staff, clinicians and clinical trials staff, etc). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase, the plan to translate the research product into a clinical-grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States, this is done by filing an IND application with the Food and Drug Administration. The National Heart, Lung and Blood Institute-funded Production Assistance for Cellular Therapies program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five Production Assistance for Cellular Therapies facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A cascade reaction network mimicking the basic functional steps of adaptive immune response

NASA Astrophysics Data System (ADS)

Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

2015-10-01

Biological systems use complex ‘information-processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS that we call an adaptive immune response simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system that responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner that is superficially similar to the most basic responses of the vertebrate AIS, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices.

At the Edge of Translation – Materials to Program Cells for Directed Differentiation

PubMed Central

Arany, Praveen R; Mooney, David J

2010-01-01

The rapid advancement in basic biology knowledge, especially in the stem cell field, has created new opportunities to develop biomaterials capable of orchestrating the behavior of transplanted and host cells. Based on our current understanding of cellular differentiation, a conceptual framework for the use of materials to program cells in situ is presented, namely a domino versus a switchboard model, to highlight the use of single versus multiple cues in a controlled manner to modulate biological processes. Further, specific design principles of material systems to present soluble and insoluble cues that are capable of recruiting, programming and deploying host cells for various applications are presented. The evolution of biomaterials from simple inert substances used to fill defects, to the recent development of sophisticated material systems capable of programming cells in situ is providing a platform to translate our understanding of basic biological mechanisms to clinical care. PMID:20860763

The basics of thiols and cysteines in redox biology and chemistry.

PubMed

Poole, Leslie B

2015-03-01

Cysteine is one of the least abundant amino acids, yet it is frequently found as a highly conserved residue within functional (regulatory, catalytic, or binding) sites in proteins. It is the unique chemistry of the thiol or thiolate group of cysteine that imparts to functional sites their specialized properties (e.g., nucleophilicity, high-affinity metal binding, and/or ability to form disulfide bonds). Highlighted in this review are some of the basic biophysical and biochemical properties of cysteine groups and the equations that apply to them, particularly with respect to pKa and redox potential. Also summarized are the types of low-molecular-weight thiols present in high concentrations in most cells, as well as the ways in which modifications of cysteinyl residues can impart or regulate molecular functions important to cellular processes, including signal transduction. Copyright © 2014 Elsevier Inc. All rights reserved.

Opposite cytokine synthesis by fibroblasts in contact co-culture with osteosarcoma cells compared with transwell co-cultures.

PubMed

David, Manu S; Kelly, Elizabeth; Zoellner, Hans

2013-04-01

We recently reported exchange of membrane and cytoplasm during contact co-culture between human Gingival Fibroblasts (h-GF) and SAOS-2 osteosarcoma cells, a process we termed 'cellular sipping' to reflect the manner in which cells become morphologically diverse through uptake of material from the opposing cell type, independent of genetic change. Cellular sipping is increased by Tumor Necrosis Factor-α (TNF-α), and we here show for the first time altered cytokine synthesis in contact co-culture supporting cellular sipping compared with co-culture where h-GF and SAOS-2 were separated in transwells. SAOS-2 had often undetectably low cytokine levels, while Interleukin-6 (IL-6), Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) were secreted primarily by TNF-α stimulated h-GF and basic Fibroblast Growth Factor (FGF) was prominent in h-GF lysates (p < 0.001). Contact co-cultures permitting cellular sipping had lower IL-6, G-CSF and GM-CSF levels, as well as higher lysate FGF levels compared with TNF-α treated h-GF alone (p < 0.05). The opposite was the case for co-cultures in transwells, with increased IL-6, G-CSF and GM-CSF levels (p < 0.03) and no clear difference in FGF. We thus demonstrate significant phenotypic change in cultures where cellular sipping occurs, potentially contributing to tumor inflammatory responses. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Phage M13 for the treatment of Alzheimer and Parkinson disease.

PubMed

Messing, Joachim

2016-06-01

The studies of microbes have been instrumental in combatting infectious diseases, but they have also led to great insights into basic biological mechanism like DNA replication, transcription, and translation of mRNA. In particular, the studies of bacterial viruses, also called bacteriophage, have been quite useful to study specific cellular processes because of the ease to isolate their DNA, mRNA, and proteins. Here, I review the recent discovery of how properties of the filamentous phage M13 emerge as a novel approach to combat neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

The Nucleosome Remodeling and Deacetylase (NuRD) Complex in Development and Disease

PubMed Central

Basta, Jeannine; Rauchman, Michael

2014-01-01

The Nucleosome Remodeling and Deacetylase (NuRD) complex is one of the major chromatin remodeling complexes found in cells. It plays an important role in regulating gene transcription, genome integrity and cell cycle progression. Through its impact on these basic cellular processes, increasing evidence indicates that alterations in the activity of this macromolecular complex can lead to developmental defects, oncogenesis and accelerated ageing. Recent genetic and biochemical studies have elucidated the mechanisms of NuRD action in modifying the chromatin landscape. These advances have the potential to lead to new therapeutic approaches to birth defects and cancer. PMID:24880148

8(th) Symposium on Hemostasis: Translational and Basic Science Discoveries.

PubMed

Margaritis, Paris; Key, Nigel S

2016-05-01

It has been 14 years since the first symposium on hemostasis at UNC Chapel Hill that focused primarily on the tissue factor (TF) and Factor VIIa (FVIIa) biology, biochemistry and translational work for the treatment of bleeding. Concepts, mechanistic data and therapeutic agents have since emerged that permeate not only aspects of the TF and FVIIa functions, but also broader processes in hemostasis and thrombosis. These processes involve circulating proteins, receptors, cells and cellular components that interact within the coagulation system as well as with additional systems that are dysregulated in disorders seemingly unrelated to bleeding/thrombosis. The reviews in this symposium provide the research background to understand such interactions and integrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative analysis of phosphoinositide 3-kinase (PI3K) signaling using live-cell total internal reflection fluorescence (TIRF) microscopy.

PubMed

Johnson, Heath E; Haugh, Jason M

2013-12-02

This unit focuses on the use of total internal reflection fluorescence (TIRF) microscopy and image analysis methods to study the dynamics of signal transduction mediated by class I phosphoinositide 3-kinases (PI3Ks) in mammalian cells. The first four protocols cover live-cell imaging experiments, image acquisition parameters, and basic image processing and segmentation. These methods are generally applicable to live-cell TIRF experiments. The remaining protocols outline more advanced image analysis methods, which were developed in our laboratory for the purpose of characterizing the spatiotemporal dynamics of PI3K signaling. These methods may be extended to analyze other cellular processes monitored using fluorescent biosensors. Copyright © 2013 John Wiley & Sons, Inc.

Sodium signaling and astrocyte energy metabolism.

PubMed

Chatton, Jean-Yves; Magistretti, Pierre J; Barros, L Felipe

2016-10-01

The Na(+) gradient across the plasma membrane is constantly exploited by astrocytes as a secondary energy source to regulate the intracellular and extracellular milieu, and discard waste products. One of the most prominent roles of astrocytes in the brain is the Na(+) -dependent clearance of glutamate released by neurons during synaptic transmission. The intracellular Na(+) load collectively generated by these processes converges at the Na,K-ATPase pump, responsible for Na(+) extrusion from the cell, which is achieved at the expense of cellular ATP. These processes represent pivotal mechanisms enabling astrocytes to increase the local availability of metabolic substrates in response to neuronal activity. This review presents basic principles linking the intracellular handling of Na(+) following activity-related transmembrane fluxes in astrocytes and the energy metabolic pathways involved. We propose a role of Na(+) as an energy currency and as a mediator of metabolic signals in the context of neuron-glia interactions. We further discuss the possible impact of the astrocytic syncytium for the distribution and coordination of the metabolic response, and the compartmentation of these processes in cellular microdomains and subcellular organelles. Finally, we illustrate future avenues of investigation into signaling mechanisms aimed at bridging the gap between Na(+) and the metabolic machinery. GLIA 2016;64:1667-1676. © 2016 Wiley Periodicals, Inc.

Making quantitative morphological variation from basic developmental processes: where are we? The case of the Drosophila wing

PubMed Central

Alexis, Matamoro-Vidal; Isaac, Salazar-Ciudad; David, Houle

2015-01-01

One of the aims of evolutionary developmental biology is to discover the developmental origins of morphological variation. The discipline has mainly focused on qualitative morphological differences (e.g., presence or absence of a structure) between species. Studies addressing subtle, quantitative variation are less common. The Drosophila wing is a model for the study of development and evolution, making it suitable to investigate the developmental mechanisms underlying the subtle quantitative morphological variation observed in nature. Previous reviews have focused on the processes involved in wing differentiation, patterning and growth. Here, we investigate what is known about how the wing achieves its final shape, and what variation in development is capable of generating the variation in wing shape observed in nature. Three major developmental stages need to be considered: larval development, pupariation, and pupal development. The major cellular processes involved in the determination of tissue size and shape are cell proliferation, cell death, oriented cell division and oriented cell intercalation. We review how variation in temporal and spatial distribution of growth and transcription factors affects these cellular mechanisms, which in turn affects wing shape. We then discuss which aspects of the wing morphological variation are predictable on the basis of these mechanisms. PMID:25619644

Magnetogenetics: Remote Control of Cellular Signaling with Magnetic Fields

NASA Astrophysics Data System (ADS)

Sauer, Jeremy P.

Means for temporally regulating gene expression and cellular activity are invaluable for elucidating the underlying physiological processes and have therapeutic implications. Here we report the development of a system for remote regulation of gene expression by low frequency radiowaves (RF) or by a static magnetic field. We accomplished this by first adding iron oxide nanoparticles - either exogenously or as genetically encoded ferritin/ferric oxyhydroxide particle. These particles have been designed with affinity to the plasma membrane ion channel Transient Receptor Potential Vanilloid 1 (TRPV1) by a conjugated antibody. Application of a magnetic field stimulates the particle to gate the ion channel and this, in turn, initiates calcium-dependent transgene expression. We first demonstrated in vitro that TRPV1 can be actuated to cause calcium flux into the cell by directly applying a localized magnetic field. In mice expressing these genetically encoded components, application of external magnetic field caused remote stimulation of insulin transgene expression and significantly lowered blood glucose. In addition, we are investigating mechanisms by which iron oxide nanoparticles can absorb RF, and transduce this energy to cause channel opening. This robust, repeatable method for remote cellular regulation in vivo may ultimately have applications in basic science, as well as in technology and therapeutics.

Functions of the cellular prion protein, the end of Moore's law, and Ockham's razor theory.

PubMed

del Río, José A; Gavín, Rosalina

2016-01-01

Since its discovery the cellular prion protein (encoded by the Prnp gene) has been associated with a large number of functions. The proposed functions rank from basic cellular processes such as cell cycle and survival to neural functions such as behavior and neuroprotection, following a pattern similar to that of Moore's law for electronics. In addition, particular interest is increasing in the participation of Prnp in neurodegeneration. However, in recent years a redefinition of these functions has begun, since examples of previously attributed functions were increasingly re-associated with other proteins. Most of these functions are linked to so-called "Prnp-flanking genes" that are close to the genomic locus of Prnp and which are present in the genome of some Prnp mouse models. In addition, their role in neuroprotection against convulsive insults has been confirmed in recent studies. Lastly, in recent years a large number of models indicating the participation of different domains of the protein in apoptosis have been uncovered. However, after more than 10 years of molecular dissection our view is that the simplest mechanistic model in PrP(C)-mediated cell death should be considered, as Ockham's razor theory suggested.

The Vertebrate Brain, Evidence of Its Modular Organization and Operating System: Insights into the Brain's Basic Units of Structure, Function, and Operation and How They Influence Neuronal Signaling and Behavior

PubMed Central

Baslow, Morris H.

2011-01-01

The human brain is a complex organ made up of neurons and several other cell types, and whose role is processing information for use in eliciting behaviors. However, the composition of its repeating cellular units for both structure and function are unresolved. Based on recent descriptions of the brain's physiological “operating system”, a function of the tri-cellular metabolism of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy, and on the nature of “neuronal words and languages” for intercellular communication, insights into the brain's modular structural and functional units have been gained. In this article, it is proposed that the basic structural unit in brain is defined by its physiological operating system, and that it consists of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular system endothelial cells. It is also proposed that the basic functional unit in the brain is defined by how neurons communicate, and consists of two neurons and their interconnecting dendritic–synaptic–dendritic field. Since a functional unit is composed of two neurons, it requires two structural units to form a functional unit. Thus, the brain can be envisioned as being made up of the three-dimensional stacking and intertwining of myriad structural units which results not only in its gross structure, but also in producing a uniform distribution of binary functional units. Since the physiological NAA–NAAG operating system for supply of energy is repeated in every structural unit, it is positioned to control global brain function. PMID:21720525

An introduction to the molecular basics of aryl hydrocarbon receptor biology.

PubMed

Abel, Josef; Haarmann-Stemmann, Thomas

2010-11-01

Depending on their chemical structure and properties, environmental chemicals and other xenobiotics that enter the cell can affect cellular function by either nonselective binding to cellular macromolecules or by interference with cellular receptors, which would initiate a more defined cell biological response. One of these intracellular chemosensor molecules is the aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family that is known to mediate the biochemical and toxic effects of dioxins, polyaromatic hydrocarbons and related compounds. Numerous investigations have revealed that the AhR is not only a master regulator of drug metabolism activated by anthropogenic chemicals, but is also triggered by natural and endogenous ligands and can influence cell biological endpoints such as growth and differentiation. Cutting-edge research has identified new intriguing functions of the AhR, such as during proteasomal degradation of steroid hormone receptors, the cellular UVB stress response and the differentiation of certain T-cell subsets. In this review we provide both a survey of the fundamental basics of AhR biology and an insight into new functional aspects of AhR signaling to further stimulate research on this intriguing transcription factor at the interface between toxicology, cell biology and immunology.

The challenge of understanding the brain: where we stand in 2015

PubMed Central

Lisman, John

2015-01-01

Starting with the work of Cajal more than 100 years ago, neuroscience has sought to understand how the cells of the brain give rise to cognitive functions. How far has neuroscience progressed in this endeavor? This Perspective assesses progress in elucidating five basic brain processes: visual recognition, long-term memory, short-term memory, action selection, and motor control. Each of these processes entails several levels of analysis: the behavioral properties, the underlying computational algorithm, and the cellular/network mechanisms that implement that algorithm. At this juncture, while many questions remain unanswered, achievements in several areas of research have made it possible to relate specific properties of brain networks to cognitive functions. What has been learned reveals, at least in rough outline, how cognitive processes can be an emergent property of neurons and their connections. PMID:25996132

There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

PubMed Central

2011-01-01

Background Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator. PMID:22206406

Altered cellular localization and hemichannel activities of KID syndrome associated connexin26 I30N and D50Y mutations.

PubMed

Aypek, Hande; Bay, Veysel; Meşe, Gülistan

2016-02-02

Gap junctions facilitate exchange of small molecules between adjacent cells, serving a crucial function for the maintenance of cellular homeostasis. Mutations in connexins, the basic unit of gap junctions, are associated with several human hereditary disorders. For example, mutations in connexin26 (Cx26) cause both non-syndromic deafness and syndromic deafness associated with skin abnormalities such as keratitis-ichthyosis-deafness (KID) syndrome. These mutations can alter the formation and function of gap junction channels through different mechanisms, and in turn interfere with various cellular processes leading to distinct disorders. The KID associated Cx26 mutations were mostly shown to result in elevated hemichannel activities. However, the effects of these aberrant hemichannels on cellular processes are recently being deciphered. Here, we assessed the effect of two Cx26 mutations associated with KID syndrome, Cx26I30N and D50Y, on protein biosynthesis and channel function in N2A and HeLa cells. Immunostaining experiments showed that Cx26I30N and D50Y failed to form gap junction plaques at cell-cell contact sites. Further, these mutations resulted in the retention of Cx26 protein in the Golgi apparatus. Examination of hemichannel function by fluorescent dye uptake assays revealed that cells with Cx26I30N and D50Y mutations had increased dye uptake compared to Cx26WT (wild-type) containing cells, indicating abnormal hemichannel activities. Cells with mutant proteins had elevated intracellular calcium levels compared to Cx26WT transfected cells, which were abolished by a hemichannel blocker, carbenoxolone (CBX), as measured by Fluo-3 AM loading and flow cytometry. Here, we demonstrated that Cx26I30N and D50Y mutations resulted in the formation of aberrant hemichannels that might result in elevated intracellular calcium levels, a process which may contribute to the hyperproliferative epidermal phenotypes of KID syndrome.

Quantum cellular automata

NASA Astrophysics Data System (ADS)

Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

1994-06-01

The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

The Biotechnology Facility for International Space Station

NASA Technical Reports Server (NTRS)

Goodwin, Thomas; Lundquist, Charles; Hurlbert, Katy; Tuxhorn, Jennifer

2004-01-01

The primary mission of the Cellular Biotechnology Program is to advance microgravity as a tool in basic and applied cell biology. The microgravity environment can be used to study fundamental principles of cell biology and to achieve specific applications such as tissue engineering. The Biotechnology Facility (BTF) will provide a state-of-the-art facility to perform cellular biotechnology research onboard the International Space Station (ISS). The BTF will support continuous operation, which will allow performance of long-duration experiments and will significantly increase the on-orbit science throughput. With the BTF, dedicated ground support, and a community of investigators, the goals of the Cellular Biotechnology Program at Johnson Space Center are to: Support approximately 400 typical investigator experiments during the nominal design life of BTF (10 years). Support a steady increase in investigations per year, starting with stationary bioreactor experiments and adding rotating bioreactor experiments at a later date. Support at least 80% of all new cellular biotechnology investigations selected through the NASA Research Announcement (NRA) process. Modular components - to allow sequential and continuous experiment operations without cross-contamination Increased cold storage capability (+4 C, -80 C, -180 C). Storage of frozen cell culture inoculum - to allow sequential investigations. Storage of post-experiment samples - for return of high quality samples. Increased number of cell cultures per investigation, with replicates - to provide sufficient number of samples for data analysis and publication of results in peer-reviewed scientific journals.

c-di-AMP: An Essential Molecule in the Signaling Pathways that Regulate the Viability and Virulence of Gram-Positive Bacteria

PubMed Central

Fahmi, Tazin; Port, Gary C.

2017-01-01

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. PMID:28783096

Cell Motility Dynamics: A Novel Segmentation Algorithm to Quantify Multi-Cellular Bright Field Microscopy Images

PubMed Central

Zaritsky, Assaf; Natan, Sari; Horev, Judith; Hecht, Inbal; Wolf, Lior; Ben-Jacob, Eshel; Tsarfaty, Ilan

2011-01-01

Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs) is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF) on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC) images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional fluorescence single-cell processing to perform objective, accurate quantitative analyses for various biological applications. PMID:22096600

Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images.

PubMed

Zaritsky, Assaf; Natan, Sari; Horev, Judith; Hecht, Inbal; Wolf, Lior; Ben-Jacob, Eshel; Tsarfaty, Ilan

2011-01-01

Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi-cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs) is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF) on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC) images on the multi-cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional fluorescence single-cell processing to perform objective, accurate quantitative analyses for various biological applications.

Gastrointestinal immune system and its disorders.

PubMed

Keren, D F

1990-01-01

Over the past 15 years the basic details of the mucosal immune response have been described. The challenge of the next decade is to expand these details and to relate this basic information to pathologic processes in the gastrointestinal tract. It is now clear that secretory IgA is the main immunoglobulin produced by the mucosa. Further, we know that oral rather than parenteral priming preferentially stimulates a secretory IgA response. IgA protects mainly by binding to an intraluminal microorganism or toxin and thereby interfering with its absorption across the gut epithelium. The cellular basis for the IgA response has also been elucidated to some degree. It is clear that the response is highly T cell dependent and requires both helper T cells and switch T cells. With the use of monoclonal antibodies, we have begun to learn about cell-mediated functions in the gut. Suppressor/cytotoxic lymphocytes are largely sequestered in the epithelium whereas helper/inducer lymphocytes mainly reside in the lamina propria. In diseases such as celiac disease and inflammatory bowel disease, several alterations in the gastrointestinal immune system have been described. Some, such as the finding of antibody to gliaden, may be causally related to the disease. Others, such as antibodies to luminal bacteria, likely are secondary events. The challenge of the next decade is to expand these details and to relate this basic information to pathologic processes along the gastrointestinal tract.

Bacterial Hsp70 (DnaK) and mammalian Hsp70 interact differently with lipid membranes.

PubMed

Lopez, Victor; Cauvi, David M; Arispe, Nelson; De Maio, Antonio

2016-07-01

The cellular response to stress is orchestrated by the expression of a family of proteins termed heat shock proteins (hsp) that are involved in the stabilization of basic cellular processes to preserve cell viability and homeostasis. The bulk of hsp function occurs within the cytosol and subcellular compartments. However, some hsp have also been found outside cells released by an active mechanism independent of cell death. Extracellular hsp act as signaling molecules directed at activating a systemic response to stress. The export of hsp requires the translocation from the cytosol into the extracellular milieu across the plasma membrane. We have proposed that membrane insertion is the initial step in this export process. We investigated the interaction of the major inducible hsp from mammalian (Hsp70) and bacterial (DnaK) species with liposomes. We found that mammalian Hsp70 displayed a high specificity for negatively charged phospholipids, such as phosphatidyl serine, whereas DnaK interacted with all lipids tested regardless of the charge. Both proteins were inserted into the lipid bilayer as demonstrated by resistance to acid or basic washes that was confirmed by partial protection from proteolytic cleavage. Several regions of mammalian Hsp70 were inserted into the membrane with a small portion of the N-terminus end exposed to the outer phase of the liposome. In contrast, the N-terminus end of DnaK was inserted into the membrane, exposing the C-terminus end outside the liposome. Mammalian Hsp70 was found to make high oligomeric complexes upon insertion into the membranes whereas DnaK only formed dimers within the lipid bilayer. These observations suggest that both Hsp70s interact with lipids, but mammalian Hsp70 displays a high degree of specificity and structure as compared with the bacterial form.

Metals and Alzheimer’s Disease: How Far Have We Come in the Clinic?

PubMed Central

Adlard, Paul A.; Bush, Ashley I.

2018-01-01

It is estimated that by the year 2050 there will be more than 1.5 billion people globally over the age of 65 years. Aging is associated with changes to a number of different cellular processes which are driven by a variety of factors that contribute to the characteristic decline in function that is seen across multiple physiological domains/tissues in the elderly (including the brain). Importantly, aging is also the primary risk factor for the development of neurodegenerative disorders such as Alzheimer’s disease. As such, there is an urgent need to provide a greater understanding of both the pathogenesis and treatment of these devastating neurodegenerative disorders. One of the key cellular processes that becomes dysregulated with age and participates both directly and indirectly in age-related dysfunction, is metal homeostasis and the neurochemistry of metalloproteins, the basic science of which has been extensively reviewed in the past. In this review, we will focus on the human clinical intervention trials that have been conducted over approximately the last four decades that have attempted to establish the efficacy of targeting metal ions in the treatment of AD. PMID:29562528

Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker's yeast fuel advances in biomedical research

PubMed Central

Levine, Beth; Klionsky, Daniel J.

2017-01-01

Autophagy is an ancient pathway in which parts of eukaryotic cells are self-digested within the lysosome or vacuole. This process has been studied for the past seven decades; however, we are only beginning to gain a molecular understanding of the key steps required for autophagy. Originally characterized as a hormonal and starvation response, we now know that autophagy has a much broader role in biology, including organellar remodeling, protein and organelle quality control, prevention of genotoxic stress, tumor suppression, pathogen elimination, regulation of immunity and inflammation, maternal DNA inheritance, metabolism, and cellular survival. Although autophagy is usually a degradative pathway, it also participates in biosynthetic and secretory processes. Given that autophagy has a fundamental role in many essential cellular functions, it is not surprising that autophagic dysfunction is associated with a wide range of human diseases. Genetic studies in various fungi, particularly Saccharomyces cerevisiae, provided the key initial breakthrough that led to an explosion of research on the basic mechanisms and the physiological connections of autophagy to health and disease. The Nobel Committee has recognized this breakthrough by the awarding of the 2016 Nobel Prize in Physiology or Medicine for research in autophagy. PMID:28039434

Complex dynamics of selection and cellular memory in adaptation to a changing environment

NASA Astrophysics Data System (ADS)

Kussell, Edo; Lin, Wei-Hsiang

We study a synthetic evolutionary system in bacteria in which an antibiotic resistance gene is controlled by a stochastic on/off switching promoter. At the population level, this system displays all the basic ingredients for evolutionary selection, including diversity, fitness differences, and heritability. At the single cell level, physiological processes can modulate the ability of selection to act. We expose the stochastic switching strains to pulses of antibiotics of different durations in periodically changing environments using microfluidics. Small populations are tracked over a large number of periods at single cell resolution, allowing the visualization and quantification of selective sweeps and counter-sweeps at the population level, as well as detailed single cell analysis. A simple model is introduced to predict long-term population growth rates from single cell measurements, and reveals unexpected aspects of population dynamics, including cellular memory that acts on a fast timescale to modulate growth rates. This work is supported by NIH Grant No. R01-GM097356.

Action potential properties are gravity dependent

NASA Astrophysics Data System (ADS)

Meissner, Klaus; Hanke, Wolfgang

2005-06-01

The functional properties of neuronal tissue critically depend on cellular composition and intercellular comunication. A basic principle of such communication found in various types of neurons is the generation of action potentials (APs). These APs depend on the presence of voltage gated ion channels and propagate along cellular processes (e.g. axons) towards target neurons or other cells. It has already been shown that the properties of ion channels depend on gravity. To discover whether the properties of APs also depend on gravity, we examined the propagation of APs in earthworms (invertebrates) and isolated nerve fibres (i.e. bundles of axons) from earthworms under conditions of micro- and macro-gravity. In a second set of experiments we could verify our results on rat axons (vertebrates). Our experiments carried out during two parabolic flight campaigns revealed that microgravity slows AP propagation velocity and macrogravity accelerates the transmission of action potentials. The relevance for live-science related questions is considerable, taking into account that altered gravity conditions might affect AP velocity in man during space flight missions.

Measurement of replication structures at the nanometer scale using super-resolution light microscopy

PubMed Central

Baddeley, D.; Chagin, V. O.; Schermelleh, L.; Martin, S.; Pombo, A.; Carlton, P. M.; Gahl, A.; Domaing, P.; Birk, U.; Leonhardt, H.; Cremer, C.; Cardoso, M. C.

2010-01-01

DNA replication, similar to other cellular processes, occurs within dynamic macromolecular structures. Any comprehensive understanding ultimately requires quantitative data to establish and test models of genome duplication. We used two different super-resolution light microscopy techniques to directly measure and compare the size and numbers of replication foci in mammalian cells. This analysis showed that replication foci vary in size from 210 nm down to 40 nm. Remarkably, spatially modulated illumination (SMI) and 3D-structured illumination microscopy (3D-SIM) both showed an average size of 125 nm that was conserved throughout S-phase and independent of the labeling method, suggesting a basic unit of genome duplication. Interestingly, the improved optical 3D resolution identified 3- to 5-fold more distinct replication foci than previously reported. These results show that optical nanoscopy techniques enable accurate measurements of cellular structures at a level previously achieved only by electron microscopy and highlight the possibility of high-throughput, multispectral 3D analyses. PMID:19864256

Experimental Studies of Quasi-Adiabatic Quantum-dot Cellular Automata

NASA Astrophysics Data System (ADS)

Orlov, Alexei; Amlani, Islamshah; Kummamuru, Ravi; Toth, Geza; Bernstein, Gary; Lent, Craig; Snider, Gregory

2000-03-01

The computational approach known as Quantum-dot Cellular Automata (QCA) uses interacting quantum dots to encode and process binary information. The first realization of a functioning QCA cell has already been reported. Recently, quasi-adiabatic switching of QCA in a metal dot system near the instantaneous ground state was proposed [1]. The advantage if this approach is that it allows both logic and addressable memory to be implemented within the QCA framework. We report on the fabrication and measurement of such a device in the Al-AlOx tunnel junction system. This basic building block consists of three metal islands connected in series by tunnel junctions, where an electron can be moved between islands by means of electrostatic perturbation on either control electrodes or adjacent cells. The cell can have three operational modes, i.e. active, locked and null, which provide a solution for ground state computing that is not susceptible to metastable states. [1] G. Toth and C. S. Lent, J. appl. Phys. 85 5, 2977-2984, 1999.

Wound repair and regeneration: mechanisms, signaling, and translation.

PubMed

Eming, Sabine A; Martin, Paul; Tomic-Canic, Marjana

2014-12-03

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body's natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. Copyright © 2014, American Association for the Advancement of Science.

Wound repair and regeneration: Mechanisms, signaling, and translation

PubMed Central

Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

2015-01-01

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

Cellular Therapies Clinical Research Roadmap: Lessons learned on how to move a cellular therapy into a clinical trial

PubMed Central

Ouseph, Stacy; Tappitake, Darah; Armant, Myriam; Wesselschmidt, Robin; Derecho, Ivy; Draxler, Rebecca; Wood, Deborah; Centanni, John M.

2014-01-01

A clinical research roadmap has been developed as a resource for researchers to identify critical areas and potential pitfalls when transitioning a cellular therapy product from the research laboratory, via and Investigational New Drug (IND) application, into early phase clinical trials. The roadmap describes four key areas; basic and preclinical research, resource development, translational research and good manufacturing practice (GMP), and IND assembly and submission. Basic and preclinical research identifies a new therapeutic concept and demonstrates its potential value using a model of the relevant disease. During resource development the appropriate specialists and the required expertise to bring this product into the clinic are identified (e.g., researchers, regulatory specialists, GMP manufacturing staff, clinicians, and clinical trials staff, etc.). Additionally, the funds required to achieve this goal (or a plan to procure them) are identified. In the next phase the plan to translate the research product into a clinical grade therapeutic is developed. Finally regulatory approval to start the trial must be obtained. In the United States this is done by filing an IND application with the Food and Drug Administration. The NHLBI-funded Production Assistance for Cellular Therapies (PACT) program has facilitated the transition of a variety of cellular therapy products from the laboratory into Phase1/2 trials. The five PACT facilities have assisted investigators by performing translational studies and GMP manufacturing to ensure that cellular products met release specifications and were manufactured safely, reproducibly, and at the appropriate scale. The roadmap resulting from this experience is the focus of this article. PMID:25484311

Pivotal Impacts of Retrotransposon Based Invasive RNAs on Evolution.

PubMed

Habibi, Laleh; Salmani, Hamzeh

2017-01-01

RNAs have long been described as the mediators of gene expression; they play a vital role in the structure and function of cellular complexes. Although the role of RNAs in the prokaryotes is mainly confined to these basic functions, the effects of these molecules in regulating the gene expression and enzymatic activities have been discovered in eukaryotes. Recently, a high-resolution analysis of the DNA obtained from different organisms has revealed a fundamental impact of the RNAs in shaping the genomes, heterochromatin formation, and gene creation. Deep sequencing of the human genome revealed that about half of our DNA is comprised of repetitive sequences (remnants of transposable element movements) expanded mostly through RNA-mediated processes. ORF2 encoded by L1 retrotransposons is a cellular reverse transcriptase which is mainly responsible for RNA invasion of various transposable elements (L1s, Alus, and SVAs) and cellular mRNAs in to the genomic DNA. In addition to increasing retroelements copy number; genomic expansion in association with centromere, telomere, and heterochromatin formation as well as pseudogene creation are the evolutionary consequences of this RNA-based activity. Threatening DNA integrity by disrupting the genes and forming excessive double strand breaks is another effect of this invasion. Therefore, repressive mechanisms have been evolved to control the activities of these invasive intracellular RNAs. All these mechanisms now have essential roles in the complex cellular functions. Therefore, it can be concluded that without direct action of RNA networks in shaping the genome and in the development of different cellular mechanisms, the evolution of higher eukaryotes would not be possible.

Pivotal Impacts of Retrotransposon Based Invasive RNAs on Evolution

PubMed Central

Habibi, Laleh; Salmani, Hamzeh

2017-01-01

RNAs have long been described as the mediators of gene expression; they play a vital role in the structure and function of cellular complexes. Although the role of RNAs in the prokaryotes is mainly confined to these basic functions, the effects of these molecules in regulating the gene expression and enzymatic activities have been discovered in eukaryotes. Recently, a high-resolution analysis of the DNA obtained from different organisms has revealed a fundamental impact of the RNAs in shaping the genomes, heterochromatin formation, and gene creation. Deep sequencing of the human genome revealed that about half of our DNA is comprised of repetitive sequences (remnants of transposable element movements) expanded mostly through RNA-mediated processes. ORF2 encoded by L1 retrotransposons is a cellular reverse transcriptase which is mainly responsible for RNA invasion of various transposable elements (L1s, Alus, and SVAs) and cellular mRNAs in to the genomic DNA. In addition to increasing retroelements copy number; genomic expansion in association with centromere, telomere, and heterochromatin formation as well as pseudogene creation are the evolutionary consequences of this RNA-based activity. Threatening DNA integrity by disrupting the genes and forming excessive double strand breaks is another effect of this invasion. Therefore, repressive mechanisms have been evolved to control the activities of these invasive intracellular RNAs. All these mechanisms now have essential roles in the complex cellular functions. Therefore, it can be concluded that without direct action of RNA networks in shaping the genome and in the development of different cellular mechanisms, the evolution of higher eukaryotes would not be possible. PMID:29067016

Effects of Simulated Weightlessness on Mammalian Development. Part 2: Meiotic Maturation of Mouse Oocytes During Clinostat Rotation

NASA Technical Reports Server (NTRS)

Wolgemuth, D. J.; Grills, G. S.

1985-01-01

In order to understand the role of gravity in basic cellular processes that are important during development, the effects of a simulated microgravity environment on mammalian gametes and early embryos cultured in vitro are examined. A microgravity environment is simulated by use of a clinostat, which essentially reorients cells relative to the gravity vector. Initial studies have focused on assessing the effects of clinostat rotation on the meiotic progression of mouse oocytes. Modifications centered on providing the unique in vitro culture of the clinostat requirements of mammalian oocytes and embryos: 37 C temperature, constant humidity, and a 5% CO2 in air environment. The oocytes are observed under the dissecting microscope for polar body formation and gross morphological appearance. They are then processed for cytogenetic analysis.

Cellular automata simulation of topological effects on the dynamics of feed-forward motifs

PubMed Central

Apte, Advait A; Cain, John W; Bonchev, Danail G; Fong, Stephen S

2008-01-01

Background Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems. Results Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production. Conclusion It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models. PMID:18304325

The Roles of Glutathione Peroxidases during Embryo Development

PubMed Central

Ufer, Christoph; Wang, Chi Chiu

2011-01-01

Embryo development relies on the complex interplay of the basic cellular processes including proliferation, differentiation, and apoptotic cell death. Precise regulation of these events is the basis for the establishment of embryonic structures and the organ development. Beginning with fertilization of the oocyte until delivery the developing embryo encounters changing environmental conditions such as varying levels of oxygen, which can give rise to reactive oxygen species (ROS). These challenges are met by the embryo with metabolic adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious by modifying biological molecules including lipids, proteins, and nucleic acids and may induce abnormal development or even embryonic lethality. On the other hand ROS are vital players of various signaling cascades that affect the balance between cell growth, differentiation, and death. An imbalance or dysregulation of these biological processes may generate cells with abnormal growth and is therefore potentially teratogenic and tumorigenic. Thus, a precise balance between processes generating ROS and those decomposing ROS is critical for normal embryo development. One tier of the cellular protective system against ROS constitutes the family of selenium-dependent glutathione peroxidases (GPx). These enzymes reduce hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. Of special interest within this protein family is the moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger of lipophilic hydroperoxides on one hand, but on the other hand can be transformed into an enzymatically inactive cellular structural component. GPx4 deficiency – in contrast to all other GPx family members – leads to abnormal embryo development and finally produces a lethal phenotype in mice. This review is aimed at summarizing the current knowledge on GPx isoforms during embryo development and tumor development with an emphasis on GPx4. PMID:21847368

The Roles of Glutathione Peroxidases during Embryo Development.

PubMed

Ufer, Christoph; Wang, Chi Chiu

2011-01-01

Embryo development relies on the complex interplay of the basic cellular processes including proliferation, differentiation, and apoptotic cell death. Precise regulation of these events is the basis for the establishment of embryonic structures and the organ development. Beginning with fertilization of the oocyte until delivery the developing embryo encounters changing environmental conditions such as varying levels of oxygen, which can give rise to reactive oxygen species (ROS). These challenges are met by the embryo with metabolic adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious by modifying biological molecules including lipids, proteins, and nucleic acids and may induce abnormal development or even embryonic lethality. On the other hand ROS are vital players of various signaling cascades that affect the balance between cell growth, differentiation, and death. An imbalance or dysregulation of these biological processes may generate cells with abnormal growth and is therefore potentially teratogenic and tumorigenic. Thus, a precise balance between processes generating ROS and those decomposing ROS is critical for normal embryo development. One tier of the cellular protective system against ROS constitutes the family of selenium-dependent glutathione peroxidases (GPx). These enzymes reduce hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. Of special interest within this protein family is the moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger of lipophilic hydroperoxides on one hand, but on the other hand can be transformed into an enzymatically inactive cellular structural component. GPx4 deficiency - in contrast to all other GPx family members - leads to abnormal embryo development and finally produces a lethal phenotype in mice. This review is aimed at summarizing the current knowledge on GPx isoforms during embryo development and tumor development with an emphasis on GPx4.

The biological effect of prolonged radiation and ways of selecting new anti-radiation drugs effective in this kind of radiation injury

NASA Technical Reports Server (NTRS)

Rogozkin, V. D.; Chertkov, K. S.; Nikolov, I.

1974-01-01

The basic characteristics of prolonged radiation - increased tolerance of radiation injury - are attributed to cellular kinetics; as dose rate is reduced, the population rate is not disturbed, particularly that of stem cells which makes it possible for the organism to tolerate higher radiation loads. It is concluded that this effect makes approved radio protectors, whose effect contains an established cytostatic component, unsuitable for prolonged radiation. It is better to correct the stem pool formation process by either accelerating the proliferation of cells or limiting the effect of stimuli causing cells to lose colony forming properties.

Hereditary spastic paraplegias: membrane traffic and the motor pathway

PubMed Central

Blackstone, Craig; O’Kane, Cahir J.; Reid, Evan

2017-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution — in axonal maintenance and degeneration. PMID:21139634

Hereditary spastic paraplegias: membrane traffic and the motor pathway.

PubMed

Blackstone, Craig; O'Kane, Cahir J; Reid, Evan

2011-01-01

Voluntary movement is a fundamental way in which animals respond to, and interact with, their environment. In mammals, the main CNS pathway controlling voluntary movement is the corticospinal tract, which encompasses connections between the cerebral motor cortex and the spinal cord. Hereditary spastic paraplegias (HSPs) are a group of genetic disorders that lead to a length-dependent, distal axonopathy of fibres of the corticospinal tract, causing lower limb spasticity and weakness. Recent work aimed at elucidating the molecular cell biology underlying the HSPs has revealed the importance of basic cellular processes — especially membrane trafficking and organelle morphogenesis and distribution— in axonal maintenance and degeneration.

Methyl jasmonate as a vital substance in plants.

PubMed

Cheong, Jong-Joo; Choi, Yang Do

2003-07-01

The plant floral scent methyl jasmonate (MeJA) has been identified as a vital cellular regulator that mediates diverse developmental processes and defense responses against biotic and abiotic stresses. The pleiotropic effects of MeJA have raised numerous questions about its regulation for biogenesis and mode of action. Characterization of the gene encoding jasmonic acid carboxyl methyltransferase has provided basic information on the role(s) of this phytohormone in gene-activation control and systemic long-distance signaling. Recent approaches using functional genomics and bioinformatics have identified a whole set of MeJA-responsive genes, and provide insights into how plants use volatile signals to withstand diverse and variable environments.

Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

PubMed

Epel, Elissa S; Lithgow, Gordon J

2014-06-01

The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[AGING AND OSTEOARTHRITIS. CHRONIC NONSPECIFIC INFLAMMATION AS A LINK BETWEEN AGING AND OSTEOARTHRITIS (REVIEW)].

PubMed

Mendel, O I; Luchihina, L V; Mendel, W

2015-01-01

This article presents review on the processes underlying aging and the most common age-associated diseases. Special attention is given to the role of chronic nonspecific inflammation. Based on the literature data it was demonstrated that aging and osteoarthritis have the same basic molecular and cellular mechanisms, among which general are cascades intracellular transcription chronic nonspecific inflammation and metabolic disturbances plays an important role. It is concluded that the process of normal aging is not a disease, but makes the human body, and particularly the musculoskeletal system, susceptible to age-associated changes. Number of changes in the human body that accompany the aging process, and play a role in the development and progression of OA, are potentially reversible, regardless of age (eg, chronic non-specific inflammation), and can be considered as a possible entry points for the effective prevention and complex therapy of OA in elderly people.

Pharmacology of Vagal Afferent Influences on Disordered Breathing During Sleep

PubMed Central

Carley, David W; Radulovacki, Miodrag

2008-01-01

Sleep related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of ∼2% of women and ∼4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. Current primary treatments are surgical or mechanical, with no drug treatments available. Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved. PMID:18694851

Cellular responses to environmental DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.

Opportunities and challenges of current electrophysiology research: a plea to establish 'translational electrophysiology' curricula.

PubMed

Lau, Dennis H; Volders, Paul G A; Kohl, Peter; Prinzen, Frits W; Zaza, Antonio; Kääb, Stefan; Oto, Ali; Schotten, Ulrich

2015-05-01

Cardiac electrophysiology has evolved into an important subspecialty in cardiovascular medicine. This is in part due to the significant advances made in our understanding and treatment of heart rhythm disorders following more than a century of scientific discoveries and research. More recently, the rapid development of technology in cellular electrophysiology, molecular biology, genetics, computer modelling, and imaging have led to the exponential growth of knowledge in basic cardiac electrophysiology. The paradigm of evidence-based medicine has led to a more comprehensive decision-making process and most likely to improved outcomes in many patients. However, implementing relevant basic research knowledge in a system of evidence-based medicine appears to be challenging. Furthermore, the current economic climate and the restricted nature of research funding call for improved efficiency of translation from basic discoveries to healthcare delivery. Here, we aim to (i) appraise the broad challenges of translational research in cardiac electrophysiology, (ii) highlight the need for improved strategies in the training of translational electrophysiologists, and (iii) discuss steps towards building a favourable translational research environment and culture. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

The hierarchical structure and mechanics of plant materials.

PubMed

Gibson, Lorna J

2012-11-07

The cell walls in plants are made up of just four basic building blocks: cellulose (the main structural fibre of the plant kingdom) hemicellulose, lignin and pectin. Although the microstructure of plant cell walls varies in different types of plants, broadly speaking, cellulose fibres reinforce a matrix of hemicellulose and either pectin or lignin. The cellular structure of plants varies too, from the largely honeycomb-like cells of wood to the closed-cell, liquid-filled foam-like parenchyma cells of apples and potatoes and to composites of these two cellular structures, as in arborescent palm stems. The arrangement of the four basic building blocks in plant cell walls and the variations in cellular structure give rise to a remarkably wide range of mechanical properties: Young's modulus varies from 0.3 MPa in parenchyma to 30 GPa in the densest palm, while the compressive strength varies from 0.3 MPa in parenchyma to over 300 MPa in dense palm. The moduli and compressive strength of plant materials span this entire range. This study reviews the composition and microstructure of the cell wall as well as the cellular structure in three plant materials (wood, parenchyma and arborescent palm stems) to explain the wide range in mechanical properties in plants as well as their remarkable mechanical efficiency.

The hierarchical structure and mechanics of plant materials

PubMed Central

Gibson, Lorna J.

2012-01-01

The cell walls in plants are made up of just four basic building blocks: cellulose (the main structural fibre of the plant kingdom) hemicellulose, lignin and pectin. Although the microstructure of plant cell walls varies in different types of plants, broadly speaking, cellulose fibres reinforce a matrix of hemicellulose and either pectin or lignin. The cellular structure of plants varies too, from the largely honeycomb-like cells of wood to the closed-cell, liquid-filled foam-like parenchyma cells of apples and potatoes and to composites of these two cellular structures, as in arborescent palm stems. The arrangement of the four basic building blocks in plant cell walls and the variations in cellular structure give rise to a remarkably wide range of mechanical properties: Young's modulus varies from 0.3 MPa in parenchyma to 30 GPa in the densest palm, while the compressive strength varies from 0.3 MPa in parenchyma to over 300 MPa in dense palm. The moduli and compressive strength of plant materials span this entire range. This study reviews the composition and microstructure of the cell wall as well as the cellular structure in three plant materials (wood, parenchyma and arborescent palm stems) to explain the wide range in mechanical properties in plants as well as their remarkable mechanical efficiency. PMID:22874093

Translational bioinformatics: linking the molecular world to the clinical world.

PubMed

Altman, R B

2012-06-01

Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.

Advanced Image Acquisition and Analytical Techniques for Studies of Living Cells and Tissue Sections.

PubMed

Franek, Michal; Suchánková, Jana; Sehnalová, Petra; Krejčí, Jana; Legartová, Soňa; Kozubek, Stanislav; Večeřa, Josef; Sorokin, Dmitry V; Bártová, Eva

2016-04-01

Studies on fixed samples or genome-wide analyses of nuclear processes are useful for generating snapshots of a cell population at a particular time point. However, these experimental approaches do not provide information at the single-cell level. Genome-wide studies cannot assess variability between individual cells that are cultured in vitro or originate from different pathological stages. Immunohistochemistry and immunofluorescence are fundamental experimental approaches in clinical laboratories and are also widely used in basic research. However, the fixation procedure may generate artifacts and prevents monitoring of the dynamics of nuclear processes. Therefore, live-cell imaging is critical for studying the kinetics of basic nuclear events, such as DNA replication, transcription, splicing, and DNA repair. This review is focused on the advanced microscopy analyses of the cells, with a particular focus on live cells. We note some methodological innovations and new options for microscope systems that can also be used to study tissue sections. Cornerstone methods for the biophysical research of living cells, such as fluorescence recovery after photobleaching and fluorescence resonance energy transfer, are also discussed, as are studies on the effects of radiation at the individual cellular level.

Stair evacuation simulation based on cellular automata considering evacuees’ walk preferences

NASA Astrophysics Data System (ADS)

Ding, Ning; Zhang, Hui; Chen, Tao; Peter, B. Luh

2015-06-01

As a physical model, the cellular automata (CA) model is widely used in many areas, such as stair evacuation. However, existing CA models do not consider evacuees’ walk preferences nor psychological status, and the structure of the basic model is unapplicable for the stair structure. This paper is to improve the stair evacuation simulation by addressing these issues, and a new cellular automata model is established. Several evacuees’ walk preference and how evacuee’s psychology influences their behaviors are introduced into this model. Evacuees’ speeds will be influenced by these features. To validate this simulation, two fire drills held in two high-rise buildings are video-recorded. It is found that the simulation results are similar to the fire drill results. The structure of this model is simple, and it is easy to further develop and utilize in different buildings with various kinds of occupants. Project supported by the National Basic Research Program of China (Grant No. 2012CB719705) and the National Natural Science Foundation of China (Grant Nos. 91224008, 91024032, and 71373139).

Cellular and molecular mechanisms regulating vascular tone. Part 1: basic mechanisms controlling cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.

PubMed

Akata, Takashi

2007-01-01

General anesthetics cause hemodynamic instability and alter blood flow to various organs. There is mounting evidence that most general anesthetics, at clinical concentrations, influence a wide variety of cellular and molecular mechanisms regulating the contractile state of vascular smooth muscle cells (i.e., vascular tone). In addition, in current anesthetic practice, various types of vasoactive agents are often used to control vascular reactivity and to sustain tissue blood flow in high-risk surgical patients with impaired vital organ function and/or hemodynamic instability. Understanding the physiological mechanisms involved in the regulation of vascular tone thus would be beneficial for anesthesiologists. This review, in two parts, provides an overview of current knowledge about the cellular and molecular mechanisms regulating vascular tone-i.e., targets for general anesthetics, as well as for vasoactive drugs that are used in intraoperative circulatory management. This first part of the two-part review focuses on basic mechanisms regulating cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone.

HIV-1 tat protein recruits CIS to the cytoplasmic tail of CD127 to induce receptor ubiquitination and proteasomal degradation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugden, Scott, E-mail: scott.sugden@ircm.qc.ca

HIV-1 Tat protein down regulates expression of the IL-7 receptor alpha-chain (CD127) from the surface of CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. We have previously shown that soluble Tat protein is taken up by CD8 T cells and interacts with the cytoplasmic tail of CD127 to induce receptor degradation. The N-terminal domain of Tat interacts with CD127 while the basic domain directs CD127 to the proteasome. We have also shown that upon IL-7 binding to its receptor, CD127 is phosphorylated resulting in CIS-mediated proteasomal degradation. Here, we show that Tat mimics this process bymore » recruiting CIS to CD127 in the absence of IL-7 and receptor phosphorylation, leading to CD127 ubiquitination and degradation. Tat therefore acts as an adapter to induce cellular responses under conditions where they may not otherwise occur. Thusly, Tat reduces IL-7 signaling and impairs CD8 T cell survival and function. -- Highlights: •Soluble HIV-1 Tat decreases CD127 expression on CD8 T cells, causing dysfunction. •Tat induces CD127 ubiquitination without activating IL-7 signaling. •Tat binds CD127 and recruits the E3 ubiquitin ligase CIS via its basic domain. •Tat hijacks a normal cellular mechanism to degrade CD127 without IL-7 signaling.« less

Virtual immunology: software for teaching basic immunology.

PubMed

Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

2013-01-01

As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available free of charge in Portuguese and English, which can be used by teachers and students in physiology, immunology, and cellular biology classes. We discuss the development of the initial two modules: "Organs and Lymphoid Tissues" and "Inflammation" and the use of interactive activities to provide microscopic and macroscopic understanding in immunology. Students, both graduate and undergraduate, were questioned along with university level professors about the quality of the software and intuitiveness of use, facility of navigation, and aesthetic organization using a Likert scale. An overwhelmingly satisfactory result was obtained with both students and immunology teachers. Programs such as "Virtual Immunology" are offering more interactive, multimedia approaches to complex scientific principles that increase student motivation, interest, and comprehension. © 2013 by The International Union of Biochemistry and Molecular Biology.

Migration of cells in a social context

PubMed Central

Vedel, Søren; Tay, Savaş; Johnston, Darius M.; Bruus, Henrik; Quake, Stephen R.

2013-01-01

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified “cellular traffic rules” and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells. PMID:23251032

Migration of cells in a social context.

PubMed

Vedel, Søren; Tay, Savaş; Johnston, Darius M; Bruus, Henrik; Quake, Stephen R

2013-01-02

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified "cellular traffic rules" and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

An intrinsic poperty of memory of the Cellular automaton infrastructure of Nature leading to the organization of the physical world as an Internet o things; TOE = IOT

NASA Astrophysics Data System (ADS)

Berkovich, Simon

2015-04-01

The undamental advantage of a Cellular automaton construction foris that it can be viewed as an undetectable absolute frame o reference, in accordance with Lorentz-Poincare's interpretation.. The cellular automaton model for physical poblems comes upon two basic hurdles: (1) How to find the Elemental Rule that, and how to get non-locality from local transformations. Both problems are resolved considering the transfomation rule of mutual distributed synchronization Actually any information proessing device starts with a clocking system. and it turns out that ``All physical phenomena are different aspects of the high-level description of distributed mutual synchronization in a network of digital clocks''. Non-locality comes from two hugely different time-scales of signaling.. The universe is acombinines information and matter processes, These fast spreading diffusion wave solutions create the mechanism of the Holographic Universe. And thirdly Disengaged from synchronization, circular counters can perform memory functions by retaining phases of their oscillations, an idea of Von Neumann'. Thus, the suggested model generates the necessary constructs for the physical world as an Internet of Things. Life emerges due to the specifics of macromolecules that serve as communication means, with the holographic memory...

Theoretical aspects of cellular decision-making and information-processing.

PubMed

Kobayashi, Tetsuya J; Kamimura, Atsushi

2012-01-01

Microscopic biological processes have extraordinary complexity and variety at the sub-cellular, intra-cellular, and multi-cellular levels. In dealing with such complex phenomena, conceptual and theoretical frameworks are crucial, which enable us to understand seemingly different intra- and inter-cellular phenomena from unified viewpoints. Decision-making is one such concept that has attracted much attention recently. Since a number of cellular behavior can be regarded as processes to make specific actions in response to external stimuli, decision-making can cover and has been used to explain a broad range of different cellular phenomena [Balázsi et al. (Cell 144(6):910, 2011), Zeng et al. (Cell 141(4):682, 2010)]. Decision-making is also closely related to cellular information-processing because appropriate decisions cannot be made without exploiting the information that the external stimuli contain. Efficiency of information transduction and processing by intra-cellular networks determines the amount of information obtained, which in turn limits the efficiency of subsequent decision-making. Furthermore, information-processing itself can serve as another concept that is crucial for understanding of other biological processes than decision-making. In this work, we review recent theoretical developments on cellular decision-making and information-processing by focusing on the relation between these two concepts.

Architectures and protocols for an integrated satellite-terrestrial mobile system

NASA Technical Reports Server (NTRS)

Delre, E.; Dellipriscoli, F.; Iannucci, P.; Menolascino, R.; Settimo, F.

1993-01-01

This paper aims to depict some basic concepts related to the definition of an integrated system for mobile communications, consisting of a satellite network and a terrestrial cellular network. In particular three aspects are discussed: (1) architecture definition for the satellite network; (2) assignment strategy of the satellite channels; and (3) definition of 'internetworking procedures' between cellular and satellite network, according to the selected architecture and the satellite channel assignment strategy.

A simple model of fluid flow and electrolyte balance in the body

NASA Technical Reports Server (NTRS)

White, R. J.; Neal, L.

1973-01-01

The model is basically a three-compartment model, the three compartments being the plasma, interstitial fluid and cellular fluid. Sodium, potassium, chloride and urea are the only major solutes considered explicitly. The control of body water and electrolyte distribution is affected via drinking and hormone levels. Basically, the model follows the effect of various oral input water loads on solute and water distribution throughout the body.

Functional Assays for Neurotoxicity Testing

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

Functional Assays for Neurotoxicity Testing*

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

PACS—Realization of an adaptive concept using pressure actuated cellular structures

NASA Astrophysics Data System (ADS)

Gramüller, B.; Boblenz, J.; Hühne, C.

2014-10-01

A biologically inspired concept is investigated which can be utilized to develop energy efficient, lightweight and applicational flexible adaptive structures. Building a real life morphing unit is an ambitious task as the numerous works in the particular field show. Summarizing fundamental demands and barriers regarding shape changing structures, the basic challenges of designing morphing structures are listed. The concept of Pressure Actuated Cellular Structures (PACS) is arranged within the recent morphing activities and it is shown that it complies with the underlying demands. Systematically divided into energy-related and structural subcomponents the working principle is illuminated and relationships between basic design parameters are expressed. The analytical background describing the physical mechanisms of PACS is presented in concentrated manner. This work focuses on the procedure of dimensioning, realizing and experimental testing of a single cell and a single row cantilever made of PACS. The experimental outcomes as well as the results from the FEM computations are used for evaluating the analytical methods. The functionality of the basic principle is thus validated and open issues are determined pointing the way ahead.

Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

PubMed Central

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

2013-01-01

Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

Teaching the basics of cancer metabolism: Developing antitumor strategies by exploiting the differences between normal and cancer cell metabolism.

PubMed

Kalyanaraman, Balaraman

2017-08-01

This review of the basics of cancer metabolism focuses on exploiting the metabolic differences between normal and cancer cells. The first part of the review covers the different metabolic pathways utilized in normal cells to generate cellular energy, or ATP, and the glycolytic intermediates required to build the cellular machinery. The second part of the review discusses aerobic glycolysis, or the Warburg effect, and the metabolic reprogramming involving glycolysis, tricarboxylic acid cycle, and glutaminolysis in the context of developing targeted inhibitors in cancer cells. Finally, the selective targeting of cancer mitochondrial metabolism using positively charged lipophilic compounds as potential therapeutics and their ability to mitigate the toxic side effects of conventional chemotherapeutics in normal cells are discussed. I hope this graphical review will be useful in helping undergraduate, graduate, and medical students understand how investigating the basics of cancer cell metabolism could provide new insight in developing potentially new anticancer treatment strategies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Role of the ubiquitin-proteasome system in brain ischemia: friend or foe?

PubMed

Caldeira, Margarida V; Salazar, Ivan L; Curcio, Michele; Canzoniero, Lorella M T; Duarte, Carlos B

2014-01-01

The ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitin-containing proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

A cool tool for hot and sour Archaea: proteomics of Sulfolobus solfataricus.

PubMed

Kort, Julia Christin; Esser, Dominik; Pham, Trong Khoa; Noirel, Josselin; Wright, Phillip C; Siebers, Bettina

2013-10-01

In recent years, much progress has been made in proteomic studies to unravel metabolic pathways and basic cellular processes. This is especially interesting for members of the Archaea, the third domain of life. Archaea exhibit extraordinary features and many of their cultivable representatives are adaptable to extreme environments. Archaea harbor many unique traits besides bacterial attributes, such as size, shape, and DNA structure and eukaryal characteristics like information processing. Sulfolobus solfataricus P2, a thermoacidophilic archaeal representative, is a well-established model organism adapted to low-pH environments (pH 2-3) and high temperatures (80°C). The genome has a size of 3 Mbp and its sequence has been deciphered. Approximately 3033 predicted open reading frames have been identified and the genome is characterized by a great number of diverse insertion sequence elements. In unraveling the organisms' metabolism and lifestyle, proteomic analyses have played a major role. Much effort has been directed at this organism and is reviewed here. With the help of proteomics, unique metabolic pathways were resolved in S. solfataricus, targets for regulatory protein phosphorylation identified, and cellular responses upon virus infection as well as oxidative stress analyzed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combined transcriptome and metabolome analyses of metformin effects reveal novel links between metabolic networks in steroidogenic systems.

PubMed

Udhane, Sameer S; Legeza, Balazs; Marti, Nesa; Hertig, Damian; Diserens, Gaëlle; Nuoffer, Jean-Marc; Vermathen, Peter; Flück, Christa E

2017-08-17

Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells. Microarray analysis revealed changes in 693 genes after metformin treatment. Using high resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS-NMR), we determined 38 intracellular metabolites. With bioinformatic tools we created an integrated pathway analysis to understand different intracellular processes targeted by metformin. Combined metabolomics and transcriptomics data analysis showed that metformin affects a broad range of cellular processes centered on the mitochondrium. Data confirmed several known effects of metformin on glucose and androgen metabolism, which had been identified in clinical and basic studies previously. But more importantly, novel links between the energy metabolism, sex steroid biosynthesis, the cell cycle and the immune system were identified. These omics studies shed light on a complex interplay between metabolic pathways in steroidogenic systems.

System analysis identifies distinct and common functional networks governed by transcription factor ASCL1, in glioma and small cell lung cancer.

PubMed

Donakonda, Sainitin; Sinha, Swati; Dighe, Shrinivas Nivrutti; Rao, Manchanahalli R Satyanarayana

2017-07-25

ASCL1 is a basic Helix-Loop-Helix transcription factor (TF), which is involved in various cellular processes like neuronal development and signaling pathways. Transcriptome profiling has shown that ASCL1 overexpression plays an important role in the development of glioma and Small Cell Lung Carcinoma (SCLC), but distinct and common molecular mechanisms regulated by ASCL1 in these cancers are unknown. In order to understand how it drives the cellular functional network in these two tumors, we generated a gene expression profile in a glioma cell line (U87MG) to identify ASCL1 gene targets by an si RNA silencing approach and then compared this with a publicly available dataset of similarly silenced SCLC (NCI-H1618 cells). We constructed TF-TF and gene-gene interactions, as well as protein interaction networks of ASCL1 regulated genes in glioma and SCLC cells. Detailed network analysis uncovered various biological processes governed by ASCL1 target genes in these two tumor cell lines. We find that novel ASCL1 functions related to mitosis and signaling pathways influencing development and tumor growth are affected in both glioma and SCLC cells. In addition, we also observed ASCL1 governed functional networks that are distinct to glioma and SCLC.

Influences of thermal environment on fish growth.

PubMed

Boltaña, Sebastián; Sanhueza, Nataly; Aguilar, Andrea; Gallardo-Escarate, Cristian; Arriagada, Gabriel; Valdes, Juan Antonio; Soto, Doris; Quiñones, Renato A

2017-09-01

Thermoregulation in ectothermic animals is influenced by the ability to effectively respond to thermal variations. While it is known that ectotherms are affected by thermal changes, it remains unknown whether physiological and/or metabolic traits are impacted by modifications to the thermal environment. Our research provides key evidence that fish ectotherms are highly influenced by thermal variability during development, which leads to important modifications at several metabolic levels (e.g., growth trajectories, microstructural alterations, muscle injuries, and molecular mechanisms). In Atlantic salmon ( Salmo salar ), a wide thermal range (Δ T 6.4°C) during development (posthatch larvae to juveniles) was associated with increases in key thermal performance measures for survival and growth trajectory. Other metabolic traits were also significantly influenced, such as size, muscle cellularity, and molecular growth regulators possibly affected by adaptive processes. In contrast, a restricted thermal range (Δ T 1.4°C) was detrimental to growth, survival, and cellular microstructure as muscle growth could not keep pace with increased metabolic demands. These findings provide a possible basic explanation for the effects of thermal environment during growth. In conclusion, our results highlight the key role of thermal range amplitude on survival and on interactions with major metabolism-regulating processes that have positive adaptive effects for organisms.

[Fatty acids composition of cellular lipids of the collected and newly isolated Pseudomonas lupini strains].

PubMed

Hvozdiak, R I; Dankevych, L A; Votselko, S K; Holubets', O V

2005-01-01

Fatty acid composition of cellular lipids of 23 Pseudomonas lupini strains (Beltjukova et Koroljova 1968) has been investigated. Cellular fatty acids which contained from C10 to C19 carbon atoms have been identified. Basic fatty acid of those Pseudomonas cells are hexadecanoic, hexadecenoic and octadecanoic acids. The 3-hydroxydecanoic (C10:0 3OH), 3-hydroxydodecanoic (C12:0 3OH), 2-hydroxydodecanoic (C12:0 2OH) and cyclopropane fatty acids which contain 17 and 19 carbon atoms have been detected in cellular lipids. The cellular fatty acids spectra of 22 P. lupini strains are similar to cellular fatty acids spectrum of the type strain Pseudomonas syringae pv. syringae 8511. Pathogenic isolate 2, which fatty acid content of cell lipids significantly differ from lipids of cell fatty acids from P. lupini strains and cell lipids of fatty acids of typical strains Pseudomonas syringae pv. syringae 8511 and Pseudomonas savastanoi pv. phaseolicola 9066 is the exception.

Mitochondria targeting by environmental stressors: Implications for redox cellular signaling.

PubMed

Blajszczak, Chuck; Bonini, Marcelo G

2017-11-01

Mitochondria are cellular powerhouses as well as metabolic and signaling hubs regulating diverse cellular functions, from basic physiology to phenotypic fate determination. It is widely accepted that reactive oxygen species (ROS) generated in mitochondria participate in the regulation of cellular signaling, and that some mitochondria chronically operate at a high ROS baseline. However, it is not completely understood how mitochondria adapt to persistently high ROS states and to environmental stressors that disturb the redox balance. Here we will review some of the current concepts regarding how mitochondria resist oxidative damage, how they are replaced when excessive oxidative damage compromises function, and the effect of environmental toxicants (i.e. heavy metals) on the regulation of mitochondrial ROS (mtROS) production and subsequent impact. Copyright © 2017 Elsevier B.V. All rights reserved.

Methods of synthesizing hydroxyapatite powders and bulk materials

DOEpatents

Luo, Ping

1999-01-12

Methods are provided for producing non-porous controlled morphology hydroxyapatite granules of less than 8 .mu.m by a spray-drying process. Solid or hollow spheres or doughnuts can be formed by controlling the volume fraction and viscosity of the slurry as well as the spray-drying conditions. Methods of providing for homogenous cellular structure hydroxyapatite granules are also provided. Pores or channels or varying size and number can be formed by varying the temperature at which a hydroxyapatite slurry formed in basic, saturated ammonium hydroxide is spray-dried. Methods of providing non-porous controlled morphology hydroxyapatite granules in ammonium hydroxide are also provided. The hydroxyapatite granules and bulk materials formed by these methods are also provided.

Methods of synthesizing hydroxyapatite powders and bulk materials

DOEpatents

Luo, P.

1999-01-12

Methods are provided for producing non-porous controlled morphology hydroxyapatite granules of less than 8 {micro}m by a spray-drying process. Solid or hollow spheres or doughnuts can be formed by controlling the volume fraction and viscosity of the slurry as well as the spray-drying conditions. Methods of providing for homogeneous cellular structure hydroxyapatite granules are also provided. Pores or channels or varying size and number can be formed by varying the temperature at which a hydroxyapatite slurry formed in basic, saturated ammonium hydroxide is spray-dried. Methods of providing non-porous controlled morphology hydroxyapatite granules in ammonium hydroxide are also provided. The hydroxyapatite granules and bulk materials formed by these methods are also provided. 26 figs.

Mechanics and Activation of Unconventional Myosins.

PubMed

Batters, Christopher; Veigel, Claudia

2016-08-01

Many types of cellular motility are based on the myosin family of motor proteins ranging from muscle contraction to exo- and endocytosis, cytokinesis, cell locomotion or signal transduction in hearing. At the center of this wide range of motile processes lies the adaptation of the myosins for each specific mechanical task and the ability to coordinate the timing of motor protein mobilization and targeting. In recent years, great progress has been made in developing single molecule technology to characterize the diverse mechanical properties of the unconventional myosins. Here, we discuss the basic mechanisms and mechanical adaptations of unconventional myosins, and emerging principles regulating motor mobilization and targeting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prospects for discovery by epigenome comparison

PubMed Central

Milosavljevic, Aleksandar

2010-01-01

Epigenomic analysis efforts have so far focused on the multiple layers of epigenomic information within individual cell types. With the rapidly increasing diversity of epigenomically mapped cell types, unprecedented opportunities for comparative analysis of epigenomes are opening up. One such opportunity is to map the bifurcating tree of cellular differentiation. Another is to understand the epigenomically mediated effects of mutations, environmental influences, and disease processes. Comparative analysis of epigenomes therefore has the potential to provide wide-ranging fresh insights into basic biology and human disease. The realization of this potential will critically depend on availability of a cyberinfrastructure that will scale with the volume of data and diversity of applications and a number of other computational challenges. PMID:20944597

CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells

PubMed Central

Kim, Eun Ji; Kang, Ki Ho; Ju, Ji Hyeon

2017-01-01

Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology—and particularly clustered regularly interspaced short palindromic repeats (CRISPR)—will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed. PMID:28049282

Cellular and Synaptic Properties of Local Inhibitory Circuits.

PubMed

Hull, Court

2017-05-01

Inhibitory interneurons play a key role in sculpting the information processed by neural circuits. Despite the wide range of physiologically and morphologically distinct types of interneurons that have been identified, common principles have emerged that have shed light on how synaptic inhibition operates, both mechanistically and functionally, across cell types and circuits. This introduction summarizes how electrophysiological approaches have been used to illuminate these key principles, including basic interneuron circuit motifs, the functional properties of inhibitory synapses, and the main roles for synaptic inhibition in regulating neural circuit function. It also highlights how some key electrophysiological methods and experiments have advanced our understanding of inhibitory synapse function. © 2017 Cold Spring Harbor Laboratory Press.

CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells.

PubMed

Kim, Eun Ji; Kang, Ki Ho; Ju, Ji Hyeon

2017-01-01

Recent advances in genome editing with programmable nucleases have opened up new avenues for multiple applications, from basic research to clinical therapy. The ease of use of the technology-and particularly clustered regularly interspaced short palindromic repeats (CRISPR)-will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. Here, we highlight the progress made in correcting gene mutations in monogenic hereditary disorders and discuss various CRISPR-associated applications, such as cancer research, synthetic biology, and gene therapy using induced pluripotent stem cells. The challenges, ethical issues, and future prospects of CRISPR-based systems for human research are also discussed.

New insights on glucosylated lipids: metabolism and functions.

PubMed

Ishibashi, Yohei; Kohyama-Koganeya, Ayako; Hirabayashi, Yoshio

2013-09-01

Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs

PubMed Central

Shen, Xiulong; Corey, David R

2018-01-01

Abstract RNA plays a central role in the expression of all genes. Because any sequence within RNA can be recognized by complementary base pairing, synthetic oligonucleotides and oligonucleotide mimics offer a general strategy for controlling processes that affect disease. The two primary antisense approaches for regulating expression through recognition of cellular RNAs are single-stranded antisense oligonucleotides and duplex RNAs. This review will discuss the chemical modifications and molecular mechanisms that make synthetic nucleic acid drugs possible. Lessons learned from recent clinical trials will be summarized. Ongoing clinical trials are likely to decisively test the adequacy of our current generation of antisense nucleic acid technologies and highlight areas where more basic research is needed. PMID:29240946

Mathematical Modeling of Cellular Metabolism.

PubMed

Berndt, Nikolaus; Holzhütter, Hermann-Georg

Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

Iron-sulfur cluster biogenesis in mammalian cells: new insights into the molecular mechanisms of cluster delivery

PubMed Central

Maio, Nunziata; Rouault, Tracey. A.

2014-01-01

Iron-sulfur (Fe-S) clusters are ancient, ubiquitous cofactors composed of iron and inorganic sulfur. The combination of the chemical reactivity of iron and sulfur, together with many variations of cluster composition, oxidation states and protein environments, enables Fe-S clusters to participate in numerous biological processes. Fe-S clusters are essential to redox catalysis in nitrogen fixation, mitochondrial respiration and photosynthesis, to regulatory sensing in key metabolic pathways (i. e. cellular iron homeostasis and oxidative stress response), and to the replication and maintenance of the nuclear genome. Fe-S cluster biogenesis is a multistep process that involves a complex sequence of catalyzed protein- protein interactions and coupled conformational changes between the components of several dedicated multimeric complexes. Intensive studies of the assembly process have clarified key points in the biogenesis of Fe-S proteins. However several critical questions still remain, such as: what is the role of frataxin? Why do some defects of Fe-S cluster biogenesis cause mitochondrial iron overload? How are specific Fe-S recipient proteins recognized in the process of Fe-S transfer? This review focuses on the basic steps of Fe-S cluster biogenesis, drawing attention to recent advances achieved on the identification of molecular features that guide selection of specific subsets of nascent Fe-S recipients by the cochaperone HSC20. Additionally, it outlines the distinctive phenotypes of human diseases due to mutations in the components of the basic pathway. PMID:25245479

Memory-Augmented Cellular Automata for Image Analysis.

DTIC Science & Technology

1978-11-01

case in which each cell has memory size proportional to the logarithm of the input size, showing the increased capabilities of these machines for executing a variety of basic image analysis and recognition tasks. (Author)

Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage

PubMed Central

Gebauer, Mathias; Saas, Joachim; Haag, Jochen; Dietz, Uwe; Takigawa, Masaharu; Bartnik, Eckart; Aigner, Thomas

2005-01-01

Osteoarthritis is the most common degenerative disorder of the modern world. However, many basic cellular features and molecular processes of the disease are poorly understood. In the present study we used oligonucleotide-based microarray analysis of genes of known or assumed relevance to the cellular phenotype to screen for relevant differences in gene expression between normal and osteoarthritic chondrocytes. Custom made oligonucleotide DNA arrays were used to screen for differentially expressed genes in normal (n = 9) and osteoarthritic (n = 10) cartilage samples. Real-time polymerase chain reaction (PCR) with gene-specific primers was used for quantification. Primary human adult articular chondrocytes and chondrosarcoma cell line HCS-2/8 were used to study changes in gene expression levels after stimulation with interleukin-1β and bone morphogenetic protein, as well as the dependence on cell differentiation. In situ hybridization with a gene-specific probe was applied to detect mRNA expression levels in fetal growth plate cartilage. Overall, more than 200 significantly regulated genes were detected between normal and osteoarthritic cartilage (P < 0.01). One of the significantly repressed genes, Tob1, encodes a protein belonging to a family involved in silencing cells in terms of proliferation and functional activity. The repression of Tob1 was confirmed by quantitative PCR and correlated to markers of chondrocyte activity and proliferation in vivo. Tob1 expression was also detected at a decreased level in isolated chondrocytes and in the chondrosarcoma cell line HCS-2/8. Again, in these cells it was negatively correlated with proliferative activity and positively with cellular differentiation. Altogether, the downregulation of the expression of Tob1 in osteoarthritic chondrocytes might be an important aspect of the cellular processes taking place during osteoarthritic cartilage degeneration. Activation, the reinitiation of proliferative activity and the loss of a stable phenotype are three major changes in osteoarthritic chondrocytes that are highly significantly correlated with the repression of Tob1 expression. PMID:15743474

Light sheet-based fluorescence microscopy (LSFM) reduces phototoxic effects and provides new means for the modern life sciences

NASA Astrophysics Data System (ADS)

Pampaloni, Francesco; Ansari, Nari; Girard, Philippe; Stelzer, Ernst H. K.

2011-07-01

Most optical technologies are applied to flat, basically two-dimensional cellular systems. However, physiological meaningful information relies on the morphology, the mechanical properties and the biochemistry of a cell's context. A cell requires the complex three-dimensional relationship to other cells. However, the observation of multi-cellular biological specimens remains a challenge. Specimens scatter and absorb light, thus, the delivery of the probing light and the collection of the signal light become inefficient; many endogenous biochemical compounds also absorb light and suffer degradation of some sort (photo-toxicity), which induces malfunction of a specimen. In conventional and confocal fluorescence microscopy, whenever a single plane, the entire specimen is illuminated. Recording stacks of images along the optical Z-axis thus illuminates the entire specimen once for each plane. Hence, cells are illuminated 10-20 and fish 100-300 times more often than they are observed. This can be avoided by changing the optical arrangement. The basic idea is to use light sheets, which are fed into the specimen from the side and overlap with the focal plane of a wide-field fluorescence microscope. In contrast to an epi-fluorescence arrangement, such an azimuthal fluorescence arrangement uses two independently operated lenses for illumination and detection. Optical sectioning and no photo-toxic damage or photo-bleaching outside a small volume close to the focal plane are intrinsic properties. Light sheet-based fluorescence microscopy (LSFM) takes advantage of modern camera technologies. LSFM can be operated with laser cutters and for fluorescence correlation spectroscopy. During the last few years, LSFM was used to record zebrafish development from the early 32-cell stage until late neurulation with sub-cellular resolution and short sampling periods (60-90 sec/stack). The recording speed was five 4-Megapixel large frames/sec with a dynamic range of 12-14 bit. We followed cell movements during gastrulation, revealed the development during cell migration processes and showed that an LSFM exposes an embryo to 200 times less energy than a conventional and 5,000 times less energy than a confocal fluorescence microscope. Most recently, we implemented incoherent structured illumination in our DSLM. The intensity modulated light sheets can be generated with dynamic frequencies and allow us to estimate the effect of the specimen on the image formation process at various depths in objects of different age.

Actin kinetics shapes cortical network structure and mechanics

PubMed Central

Fritzsche, Marco; Erlenkämper, Christoph; Moeendarbary, Emad; Charras, Guillaume; Kruse, Karsten

2016-01-01

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs. PMID:27152338

Actin kinetics shapes cortical network structure and mechanics.

PubMed

Fritzsche, Marco; Erlenkämper, Christoph; Moeendarbary, Emad; Charras, Guillaume; Kruse, Karsten

2016-04-01

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs.

Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds

PubMed Central

Martinelli, Roberta; Kamei, Masataka; Sage, Peter T.; Massol, Ramiro; Varghese, Laya; Sciuto, Tracey; Toporsian, Mourad; Dvorak, Ann M.; Kirchhausen, Tomas; Springer, Timothy A.

2013-01-01

Basic mechanisms by which cellular barriers sense and respond to integrity disruptions remain poorly understood. Despite its tenuous structure and constitutive exposure to disruptive strains, the vascular endothelium exhibits robust barrier function. We show that in response to micrometer-scale disruptions induced by transmigrating leukocytes, endothelial cells generate unique ventral lamellipodia that propagate via integrins toward and across these “micro-wounds” to close them. This novel actin remodeling activity progressively healed multiple micro-wounds in succession and changed direction during this process. Mechanical probe-induced micro-wounding of both endothelia and epithelia suggests that ventral lamellipodia formed as a response to force imbalance and specifically loss of isometric tension. Ventral lamellipodia were enriched in the Rac1 effectors cortactin, IQGAP, and p47Phox and exhibited localized production of hydrogen peroxide. Together with Apr2/3, these were functionally required for effective micro-wound healing. We propose that barrier disruptions are detected as local release of isometric tension/force unloading, which is directly coupled to reactive oxygen species–dependent self-restorative actin remodeling dynamics. PMID:23629967

The effects of distributed life cycles on the dynamics of viral infections.

PubMed

Campos, Daniel; Méndez, Vicenç; Fedotov, Sergei

2008-09-21

We explore the role of cellular life cycles for viruses and host cells in an infection process. For this purpose, we derive a generalized version of the basic model of virus dynamics (Nowak, M.A., Bangham, C.R.M., 1996. Population dynamics of immune responses to persistent viruses. Science 272, 74-79) from a mesoscopic description. In its final form the model can be written as a set of Volterra integrodifferential equations. We consider the role of distributed lifespans and a intracellular (eclipse) phase. These processes are implemented by means of probability distribution functions. The basic reproductive ratio R(0) of the infection is properly defined in terms of such distributions by using an analysis of the equilibrium states and their stability. It is concluded that the introduction of distributed delays can strongly modify both the value of R(0) and the predictions for the virus loads, so the effects on the infection dynamics are of major importance. We also show how the model presented here can be applied to some simple situations where direct comparison with experiments is possible. Specifically, phage-bacteria interactions are analyzed. The dynamics of the eclipse phase for phages is characterized analytically, which allows us to compare the performance of three different fittings proposed before for the one-step growth curve.

Keeping It All Going-Complement Meets Metabolism.

PubMed

Kolev, Martin; Kemper, Claudia

2017-01-01

The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity-indicating that complement's function is likely broader than initially anticipated-the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond "classic" immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature-mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement's emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also discuss how taking a closer look into the evolution of key complement components not only made the functional connection between complement and metabolism rather "predictable" but how it may also give clues for the discovery of additional roles for complement in basic cellular processes.

Theoretical aspects and modelling of cellular decision making, cell killing and information-processing in photodynamic therapy of cancer.

PubMed

Gkigkitzis, Ioannis

2013-01-01

The aim of this report is to provide a mathematical model of the mechanism for making binary fate decisions about cell death or survival, during and after Photodynamic Therapy (PDT) treatment, and to supply the logical design for this decision mechanism as an application of rate distortion theory to the biochemical processing of information by the physical system of a cell. Based on system biology models of the molecular interactions involved in the PDT processes previously established, and regarding a cellular decision-making system as a noisy communication channel, we use rate distortion theory to design a time dependent Blahut-Arimoto algorithm where the input is a stimulus vector composed of the time dependent concentrations of three PDT related cell death signaling molecules and the output is a cell fate decision. The molecular concentrations are determined by a group of rate equations. The basic steps are: initialize the probability of the cell fate decision, compute the conditional probability distribution that minimizes the mutual information between input and output, compute the cell probability of cell fate decision that minimizes the mutual information and repeat the last two steps until the probabilities converge. Advance to the next discrete time point and repeat the process. Based on the model from communication theory described in this work, and assuming that the activation of the death signal processing occurs when any of the molecular stimulants increases higher than a predefined threshold (50% of the maximum concentrations), for 1800s of treatment, the cell undergoes necrosis within the first 30 minutes with probability range 90.0%-99.99% and in the case of repair/survival, it goes through apoptosis within 3-4 hours with probability range 90.00%-99.00%. Although, there is no experimental validation of the model at this moment, it reproduces some patterns of survival ratios of predicted experimental data. Analytical modeling based on cell death signaling molecules has been shown to be an independent and useful tool for prediction of cell surviving response to PDT. The model can be adjusted to provide important insights for cellular response to other treatments such as hyperthermia, and diseases such as neurodegeneration.

Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

PubMed Central

Iyer, Janani; Wang, Qingyu; Le, Thanh; Pizzo, Lucilla; Grönke, Sebastian; Ambegaokar, Surendra S.; Imai, Yuzuru; Srivastava, Ashutosh; Troisí, Beatriz Llamusí; Mardon, Graeme; Artero, Ruben; Jackson, George R.; Isaacs, Adrian M.; Partridge, Linda; Lu, Bingwei; Kumar, Justin P.; Girirajan, Santhosh

2016-01-01

About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions. PMID:26994292

Female gametophyte development and double fertilization in Balsas teosinte, Zea mays subsp. parviglumis (Poaceae).

PubMed

Wu, Chi-Chih; Diggle, Pamela K; Friedman, William E

2011-09-01

Over the course of maize evolution, domestication played a major role in the structural transition of the vegetative and reproductive characteristics that distinguish it from its closest wild relative, Zea mays subsp. parviglumis (Balsas teosinte). Little is known, however, about impacts of the domestication process on the cellular features of the female gametophyte and the subsequent reproductive events after fertilization, even though they are essential components of plant sexual reproduction. In this study, we investigated the developmental and cellular features of the Balsas teosinte female gametophyte and early developing seed in order to unravel the key structural and evolutionary transitions of the reproductive process associated with the domestication of the ancestor of maize. Our results show that the female gametophyte of Balsas teosinte is a variation of the Polygonum type with proliferative antipodal cells and is similar to that of maize. The fertilization process of Balsas teosinte also is basically similar to domesticated maize. In contrast to maize, many events associated with the development of the embryo and endosperm appear to be initiated earlier in Balsas teosinte. Our study suggests that the pattern of female gametophyte development with antipodal proliferation is common among species and subspecies of Zea and evolved before maize domestication. In addition, we propose that the relatively longer duration of the free nuclear endosperm phase in maize is correlated with the development of a larger fruit (kernel or caryopsis) and with a bigger endosperm compared with Balsas teosinte.

Modification of mutagenesis initiated by ultraviolet light through posttreatment of bacteria with basic dyes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witkin, E M

1961-12-01

Post treatment with basic dyes, in concentrations that retard cell division, was found to influence the tnduction of mutations to prototrophy by UV light in a tyrosine-requirtng strain of E.Coli. Pyronin, which is unique among the dyes in tts selective affinity for RNA, was found to duplicate the effects of chloramphenicol or amino acfd deprtvatfon in causfng the rapid and irreversible loss of potential prototrophs (mutation frequency decline, or MFD). Acriflavtne, methyl green. crystal violet, methylene blue, and toluidine blue, all of which are known to combine with DNA, delay or retard the occurrence of MFD under conditions of aminomore » acid deprivation. When acriflavine is removed from its combination with cellular components by the addition of an excess of sodium deoxyrtbonucleate, MFD begins promptly. The same basic dyes that delay MFD were also found to interfere with the fixation of mutations (MF) in an amino acid- enriched medium, and to cause marked enhancement of the mutagenic potency of low doses of UV light. While showing no independent mutagenic activity for unirradiated bacteria, all the dyes except pyronin increased the yield of induced mutations signtficantly when added to the enriched medium upon which trradiated bacteria were incubated.These results were interpreted as evidence that UV light initiates mutagenesis by producing unstable changas directly in genic DNA. MFD is interpreted as a repair process, blocked by the machinery of RNA and protein synthesis and by the presence of certain basic dyes.« less

Role of basic biological sciences in clinical orthodontics: a case series.

PubMed

Davidovitch, Ze'ev; Krishnan, Vinod

2009-02-01

Orthodontic therapy is based on interaction between mechanics and biology. Basic biologic research aims at developing a better understanding of the mechanism of transformation of mechanical energy into biologic reactions, and exposing the reasons for iatrogenic tissue damage in orthodontics. Previous research has shown that inflammation is a major part of the biologic response to orthodontic forces. In inflammation, signal molecules that originate in remote diseased organs can reach strained paradental tissues and exacerbate the inflammatory process, leading to tissue damage. Our case series includes 3 patients, each having had systemic diseases and malocclusion. One had diabetes mellitus, Hashimoto's thyroiditis, and depression. Concern about the possible effect of these conditions on the well-being of the teeth and their surrounding tissues compelled the orthodontist to choose not to treat this patient. The other 2 patients had allergies, and 1 also had bronchial asthma and bruises. Although these conditions are thought to be risk factors for root resorption, these patients received orthodontic treatment for 2 and 3.5 years, respectively. At the end of treatment, both had excessive root resorption of many teeth. In 1 patient, this damage led to the loss of most maxillary teeth. Basic research should continue to address questions related to the biologic mechanisms of tooth movement on tissue, cellular, and molecular levels. Moreover, this research should continue to identify risk factors that might jeopardize the longevity of treated teeth. Such basic research should promote the development of new tissue-friendly and patient-friendly therapeutic methods.

Applying ecological and evolutionary theory to cancer: a long and winding road.

PubMed

Thomas, Frédéric; Fisher, Daniel; Fort, Philippe; Marie, Jean-Pierre; Daoust, Simon; Roche, Benjamin; Grunau, Christoph; Cosseau, Céline; Mitta, Guillaume; Baghdiguian, Stephen; Rousset, François; Lassus, Patrice; Assenat, Eric; Grégoire, Damien; Missé, Dorothée; Lorz, Alexander; Billy, Frédérique; Vainchenker, William; Delhommeau, François; Koscielny, Serge; Itzykson, Raphael; Tang, Ruoping; Fava, Fanny; Ballesta, Annabelle; Lepoutre, Thomas; Krasinska, Liliana; Dulic, Vjekoslav; Raynaud, Peggy; Blache, Philippe; Quittau-Prevostel, Corinne; Vignal, Emmanuel; Trauchessec, Hélène; Perthame, Benoit; Clairambault, Jean; Volpert, Vitali; Solary, Eric; Hibner, Urszula; Hochberg, Michael E

2013-01-01

Since the mid 1970s, cancer has been described as a process of Darwinian evolution, with somatic cellular selection and evolution being the fundamental processes leading to malignancy and its many manifestations (neoangiogenesis, evasion of the immune system, metastasis, and resistance to therapies). Historically, little attention has been placed on applications of evolutionary biology to understanding and controlling neoplastic progression and to prevent therapeutic failures. This is now beginning to change, and there is a growing international interest in the interface between cancer and evolutionary biology. The objective of this introduction is first to describe the basic ideas and concepts linking evolutionary biology to cancer. We then present four major fronts where the evolutionary perspective is most developed, namely laboratory and clinical models, mathematical models, databases, and techniques and assays. Finally, we discuss several of the most promising challenges and future prospects in this interdisciplinary research direction in the war against cancer.

Analysis and numerical simulation research of the heating process in the oven

NASA Astrophysics Data System (ADS)

Chen, Yawei; Lei, Dingyou

2016-10-01

How to use the oven to bake delicious food is the most concerned problem of the designers and users of the oven. For this intent, this paper analyzed the heat distribution in the oven based on the basic operation principles and proceeded the data simulation of the temperature distribution on the rack section. Constructing the differential equation model of the temperature distribution changes in the pan when the oven works based on the heat radiation and heat transmission, based on the idea of utilizing cellular automation to simulate heat transfer process, used ANSYS software to proceed the numerical simulation analysis to the rectangular, round-cornered rectangular, elliptical and circular pans and giving out the instantaneous temperature distribution of the corresponding shapes of the pans. The temperature distribution of the rectangular and circular pans proves that the product gets overcooked easily at the corners and edges of rectangular pans but not of a round pan.

Review article: mitogen-activated protein kinases in chronic intestinal inflammation - targeting ancient pathways to treat modern diseases.

PubMed

Waetzig, G H; Schreiber, S

2003-07-01

Conventional treatment of chronic inflammatory disorders, including inflammatory bowel diseases, employs broad-range anti-inflammatory drugs. In order to reduce the side-effects and increase the efficacy of treatment, several strategies have been developed in the last decade to interfere with intercellular and intracellular inflammatory signalling processes. The highly conserved mitogen-activated protein kinase pathways regulate most cellular processes, particularly defence mechanisms such as stress reactions and inflammation. In this review, we provide an overview of the current knowledge of the specificity and interconnection of mitogen-activated protein kinase pathways, their functions in the gut immune system and published and ongoing studies on the role of mitogen-activated protein kinases in inflammatory bowel disease. The development of mitogen-activated protein kinase inhibitors and their use for the therapy of inflammatory disorders is a paradigm of the successful bridging of the gap between basic research and clinical practice.

Enhanced cryopreservation of MSCs in microfluidic bioreactor by regulated shear flow

PubMed Central

Bissoyi, Akalabya; Bit, Arindam; Singh, Bikesh Kumar; Singh, Abhishek Kumar; Patra, Pradeep Kumar

2016-01-01

Cell-matrix systems can be stored for longer period of time by means of cryopreservation. Cell-matrix and cell-cell interaction has been found to be critical in a number of basic biological processes. Tissue structure maintenance, cell secretary activity, cellular migration, and cell-cell communication all exist because of the presence of cell interactions. This complex and co-ordinated interaction between cellular constituents, extracellular matrix and adjacent cells has been identified as a significant contributor in the overall co-ordination of tissue. The prime objective of this investigation is to evaluate the effects of shear-stress and cell-substrate interaction in successful recovery of adherent human mesenchymal-stem-cells (hMSCs). A customized microfluidic bioreactor has been used for the purpose. We have measured the changes in focal-point-adhesion (FPAs) by changing induced shear stress inside the bioreactor. The findings indicate that with increase in shear stress, FPAs increases between substrate and MSCs. Further, experimental results show that increased FPAs (4e-3 μbar) enhances the cellular survivability of adherent MSCs. Probably, for the first time involvement of focal point interaction in the outcome of cryopreservation of MSCs has been clarified, and it proved a potentially new approach for modification of cryopreservation protocol by up-regulating focal point of cells to improve its clinical application. PMID:27748463

Activation of AMP-activated protein kinase in response to temperature elevation shows seasonal variation in the zebra mussel, Dreissena polymorpha.

PubMed

Jost, Jennifer A; Keshwani, Sarah S; Abou-Hanna, Jacob J

2015-04-01

Global climate change is affecting ectothermic species, and a variety of studies are needed on thermal tolerances, especially from cellular and physiological perspectives. This study utilized AMP-activated protein kinase (AMPK), a key regulator of cellular energy levels, to examine the effects of high water temperatures on zebra mussel (Dreissena polymorpha) physiology. During heating, AMPK activity increased as water temperature increased to a point, and maximum AMPK activity was detected at high, but sublethal, water temperatures. This pattern varied with season, suggesting that cellular mechanisms of seasonal thermal acclimatization affect basic metabolic processes during sublethal heat stress. There was a greater seasonal variation in the water temperature at which maximum AMPK activity was measured than in lethal water temperature. Furthermore, baseline AMPK activity varied significantly across seasons, most likely reflecting altered metabolic states during times of growth and reproduction. In addition, when summer-collected mussels were lab-acclimated to winter and spring water temperatures, patterns of heat stress mirrored those of field-collected animals. These data suggest that water temperature is the main driver of the seasonal variation in physiology. This study concluded that AMPK activity, which reflects changes in energy supply and demand during heat stress, can serve as a sensitive and early indicator of temperature stress in mussels. Copyright © 2014 Elsevier Inc. All rights reserved.

How synthetic membrane systems contribute to the understanding of lipid-driven endocytosis.

PubMed

Schubert, Thomas; Römer, Winfried

2015-11-01

Synthetic membrane systems, such as giant unilamellar vesicles and solid supported lipid bilayers, have widened our understanding of biological processes occurring at or through membranes. Artificial systems are particularly suited to study the inherent properties of membranes with regard to their components and characteristics. This review critically reflects the emerging molecular mechanism of lipid-driven endocytosis and the impact of model membrane systems in elucidating the complex interplay of biomolecules within this process. Lipid receptor clustering induced by binding of several toxins, viruses and bacteria to the plasma membrane leads to local membrane bending and formation of tubular membrane invaginations. Here, lipid shape, and protein structure and valency are the essential parameters in membrane deformation. Combining observations of complex cellular processes and their reconstitution on minimal systems seems to be a promising future approach to resolve basic underlying mechanisms. This article is part of a Special Issue entitled: Mechanobiology. Copyright © 2015 Elsevier B.V. All rights reserved.

Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR.

PubMed

Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

2015-08-01

Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue.

Increased efficacy of VX-809 in different cellular systems results from an early stabilization effect of F508del-CFTR

PubMed Central

Farinha, Carlos M; Sousa, Marisa; Canato, Sara; Schmidt, André; Uliyakina, Inna; Amaral, Margarida D

2015-01-01

Cystic fibrosis (CF), the most common recessive autosomal disease among Caucasians, is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. The most common mutation, F508del, leads to CFTR impaired plasma membrane trafficking. Therapies modulating CFTR basic defect are emerging, such as VX-809, a corrector of F508del-CFTR traffic which just succeeded in a Phase III clinical trial. We recently showed that VX-809 is additive to two other correctors (VRT-325 and compound 4a). Here, we aimed to determine whether the differential rescuing by these compounds results from cell-specific factors or rather from distinct effects at the early biogenesis and/or processing. The rescuing efficiencies of the above three correctors were first compared in different cellular models (primary respiratory cells, cystic fibrosis bronchial epithelial and baby hamster kidney [BHK] cell lines) by functional approaches: micro-Ussing chamber and iodide efflux. Next, biochemical methods (metabolic labeling, pulse-chase and immunoprecipitation) were used to determine their impact on CFTR biogenesis / processing. Functional analyses revealed that VX-809 has the greatest rescuing efficacy and that the relative efficiencies of the three compounds are essentially maintained in all three cellular models tested. Nevertheless, biochemical data show that VX-809 significantly stabilizes F508del-CFTR immature form, an effect that is not observed for C3 nor C4. VX-809 and C3 also significantly increase accumulation of immature CFTR. Our data suggest that VX-809 increases the stability of F508del-CFTR immature form at an early phase of its biogenesis, thus explaining its increased efficacy when inducing its rescue. PMID:26171232

H2S, a novel therapeutic target in renal-associated diseases?

PubMed

Pan, Wen-Jun; Fan, Wen-Jing; Zhang, Chi; Han, Dan; Qu, Shun-Lin; Jiang, Zhi-Sheng

2015-01-01

For more than a century, hydrogen sulfide (H2S) has been regarded as a toxic gas. Recently, the understanding of the biological effects of H2S has been changed. This review surveys the growing recognition of H2S as an endogenous signaling molecule in mammals, with emphasis on its physiological and pathological pathways in the urinary system. This article reviews recent progress of basic and pharmacological researches related to endogenous H2S in urinary system, including the regulatory effects of H2S in the process of antioxidant, inflammation, cellular matrix remodeling and ion channels, and the role of endogenous H2S pathway in the pathogenesis of renal and urogenital disorders. Copyright © 2014. Published by Elsevier B.V.

Regulation of autophagy by amino acid availability in S. cerevisiae and mammalian cells.

PubMed

Abeliovich, Hagai

2015-10-01

Autophagy is a catabolic membrane-trafficking process that occurs in all eukaryotic organisms analyzed to date. The study of autophagy has exploded over the last decade or so, branching into numerous aspects of cellular and organismal physiology. From basic functions in starvation and quality control, autophagy has expanded into innate immunity, aging, neurological diseases, redox regulation, and ciliogenesis, to name a few roles. In the present review, I would like to narrow the discussion to the more classical roles of autophagy in supporting viability under nutrient limitation. My aim is to provide a semblance of a historical overview, together with a concise, and perhaps subjective, mechanistic and functional analysis of the central questions in the autophagy field.

Infant discrimination of rapid auditory cues predicts later language impairment.

PubMed

Benasich, April A; Tallal, Paula

2002-10-17

The etiology and mechanisms of specific language impairment (SLI) in children are unknown. Differences in basic auditory processing abilities have been suggested to underlie their language deficits. Studies suggest that the neuropathology, such as atypical patterns of cerebral lateralization and cortical cellular anomalies, implicated in such impairments likely occur early in life. Such anomalies may play a part in the rapid processing deficits seen in this disorder. However, prospective, longitudinal studies in infant populations that are critical to examining these hypotheses have not been done. In the study described, performance on brief, rapidly-presented, successive auditory processing and perceptual-cognitive tasks were assessed in two groups of infants: normal control infants with no family history of language disorders and infants from families with a positive family history for language impairment. Initial assessments were obtained when infants were 6-9 months of age (M=7.5 months) and the sample was then followed through age 36 months. At the first visit, infants' processing of rapid auditory cues as well as global processing speed and memory were assessed. Significant differences in mean thresholds were seen in infants born into families with a history of SLI as compared with controls. Examination of relations between infant processing abilities and emerging language through 24 months-of-age revealed that threshold for rapid auditory processing at 7.5 months was the single best predictor of language outcome. At age 3, rapid auditory processing threshold and being male, together predicted 39-41% of the variance in language outcome. Thus, early deficits in rapid auditory processing abilities both precede and predict subsequent language delays. These findings support an essential role for basic nonlinguistic, central auditory processes, particularly rapid spectrotemporal processing, in early language development. Further, these findings provide a temporal diagnostic window during which future language impairments may be addressed.

Microfluidic tools for cell biological research

PubMed Central

Velve-Casquillas, Guilhem; Le Berre, Maël; Piel, Matthieu; Tran, Phong T.

2010-01-01

Summary Microfluidic technology is creating powerful tools for cell biologists to control the complete cellular microenvironment, leading to new questions and new discoveries. We review here the basic concepts and methodologies in designing microfluidic devices, and their diverse cell biological applications. PMID:21152269

Basophil (close-up) (image)

MedlinePlus

... a specific type of white blood cell. These cells are readily stained with basic dyes (this is where the name comes from). Note the dark grains inside the cellular fluid (cytoplasm) of this ... white blood cells but are important parts of the body's immune ...

Ribosome Synthesis and MAPK Activity Modulate Ionizing Radiation-Induced Germ Cell Apoptosis in Caenorhabditis elegans

PubMed Central

Eberhard, Ralf; Stergiou, Lilli; Hofmann, E. Randal; Hofmann, Jen; Haenni, Simon; Teo, Youjin; Furger, André; Hengartner, Michael O.

2013-01-01

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. PMID:24278030

Exopolysaccharides produced by marine bacteria and their applications as glycosaminoglycan-like molecules.

NASA Astrophysics Data System (ADS)

Delbarre-Ladrat, Christine; Sinquin, Corinne; Lebellenger, Lou; Zykwinska, Agata; Colliec-Jouault, Sylvia

2014-10-01

Although polysaccharides are ubiquitous and the most abundant renewable bio-components, their studies, covered by the glycochemistry and glycobiology fields, remain a challenge due to their high molecular diversity and complexity. Polysaccharides are industrially used in food products; human therapeutics fall into a more recent research field and pharmaceutical industry is looking for more and more molecules with enhanced activities. Glycosaminoglycans (GAGs) found in animal tissues play a critical role in cellular physiological and pathological processes as they bind many cellular components. Therefore, they present a great potential for the design and preparation of therapeutic drugs. On the other hand, microorganisms producing exopolysaccharides (EPS) are renewable resources meeting well the actual industrial demand. In particular, the diversity of marine microorganisms is still largely unexplored offering great opportunities to discover high value products such as new molecules and biocatalysts. EPS-producing bacteria from the marine environment will be reviewed with a focus on marine-derived EPS from bacteria isolated from deep-sea hydrothermal vents. Information on chemical and structural features, putative pathways of biosynthesis, novel strategies for chemical and enzymatic modifications and potentialities in the biomedical field will be provided. An integrated approach should be used to increase the basic knowledge on these compounds and their applications; new clean environmentally friendly processes for the production of carbohydrate bio-active compounds should also be proposed for a sustainable industry.

Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores.

PubMed

Lass, Achim; Zimmermann, Robert; Oberer, Monika; Zechner, Rudolf

2011-01-01

Lipolysis is the biochemical pathway responsible for the catabolism of triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage of TAG generates non-esterified fatty acids, which are subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, it is most abundant, however, in white and brown adipose tissue. Over the last 5years, important enzymes and regulatory protein factors involved in lipolysis have been identified. These include an essential TAG hydrolase named adipose triglyceride lipase (ATGL) [annotated as patatin-like phospholipase domain-containing protein A2], the ATGL activator comparative gene identification-58 [annotated as α/β hydrolase containing protein 5], and the ATGL inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive lipase [annotated as lipase E] and monoglyceride lipase, these proteins constitute the basic "lipolytic machinery". Additionally, a large number of hormonal signaling pathways and lipid droplet-associated protein factors regulate substrate access and the activity of the "lipolysome". This review summarizes the current knowledge concerning the enzymes and regulatory processes governing lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will be given to ATGL, its regulation, and physiological function. Copyright © 2010 Elsevier Ltd. All rights reserved.

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

PubMed Central

2013-01-01

Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease. PMID:23899561

Exopolysaccharides produced by marine bacteria and their applications as glycosaminoglycan-like molecules.

PubMed

Delbarre-Ladrat, Christine; Sinquin, Corinne; Lebellenger, Lou; Zykwinska, Agata; Colliec-Jouault, Sylvia

2014-01-01

Although polysaccharides are ubiquitous and the most abundant renewable bio-components, their studies, covered by the glycochemistry and glycobiology fields, remain a challenge due to their high molecular diversity and complexity. Polysaccharides are industrially used in food products; human therapeutics fall into a more recent research field and pharmaceutical industry is looking for more and more molecules with enhanced activities. Glycosaminoglycans (GAGs) found in animal tissues play a critical role in cellular physiological and pathological processes as they bind many cellular components. Therefore, they present a great potential for the design and preparation of therapeutic drugs. On the other hand, microorganisms producing exopolysaccharides (EPS) are renewable resources meeting well the actual industrial demand. In particular, the diversity of marine microorganisms is still largely unexplored offering great opportunities to discover high value products such as new molecules and biocatalysts. EPS-producing bacteria from the marine environment will be reviewed with a focus on marine-derived EPS from bacteria isolated from deep-sea hydrothermal vents. Information on chemical and structural features, putative pathways of biosynthesis, novel strategies for chemical and enzymatic modifications and potentialities in the biomedical field will be provided. An integrated approach should be used to increase the basic knowledge on these compounds and their applications; new clean environmentally friendly processes for the production of carbohydrate bioactive compounds should also be proposed for a sustainable industry.

Processing Characteristics and Properties of the Cellular Products Made by Using Special Foaming Agents

NASA Astrophysics Data System (ADS)

Garbacz, Tomasz; Dulebova, Ludmila

2012-12-01

The paper describes the manufacturing process of extruded products by the cellular extrusion method, and presents specifications of the blowing agents used in the extrusion process as well as process conditions. The process of cellular extrusion of thermoplastic materials is aimed at obtaining cellular shapes and coats with reduced density, presenting no hollows on the surface of extruder product and displaying minimal contraction under concurrent maintenance of properties similar to properties of products extruded by means of the conventional method. In order to obtain cellular structure, the properties of extruded product are modified by applying suitable plastic or inserting auxiliary agents.

[The Biology of Learning].

PubMed

Campo-Cabal, Gerardo

2012-01-01

The effort to relate mental and biological functioning has fluctuated between two doctrines: 1) an attempt to explain mental functioning as a collective property of the brain and 2) as one relatied to other mental processes associated with specific regions of the brain. The article reviews the main theories developed over the last 200 years: phrenology, the psuedo study of the brain, mass action, cellular connectionism and distributed processing among others. In addition, approaches have emerged in recent years that allows for an understanding of the biological determinants and individual differences in complex mental processes through what is called cognitive neuroscience. Knowing the definition of neuroscience, the learning of memory, the ways in which learning occurs, the principles of the neural basis of memory and learning and its effects on brain function, among other things, allows us the basic understanding of the processes of memory and learning and is an important requirement to address the best manner to commit to the of training future specialists in Psychiatry. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The Biotechnology Facility for International Space Station.

PubMed

Goodwin, Thomas; Lundquist, Charles; Tuxhorn, Jennifer; Hurlbert, Katy

2004-03-01

The primary mission of the Cellular Biotechnology Program is to advance microgravity as a tool in basic and applied cell biology. The microgravity environment can be used to study fundamental principles of cell biology and to achieve specific applications such as tissue engineering. The Biotechnology Facility (BTF) will provide a state-of-the-art facility to perform cellular biotechnology research onboard the International Space Station (ISS). The BTF will support continuous operation, which will allow performance of long-duration experiments and will significantly increase the on-orbit science throughput.

The Biotechnology Facility for International Space Station

NASA Technical Reports Server (NTRS)

Goodwin, Thomas; Lundquist, Charles; Tuxhorn, Jennifer; Hurlbert, Katy

2004-01-01

The primary mission of the Cellular Biotechnology Program is to advance microgravity as a tool in basic and applied cell biology. The microgravity environment can be used to study fundamental principles of cell biology and to achieve specific applications such as tissue engineering. The Biotechnology Facility (BTF) will provide a state-of-the-art facility to perform cellular biotechnology research onboard the International Space Station (ISS). The BTF will support continuous operation, which will allow performance of long-duration experiments and will significantly increase the on-orbit science throughput.

Mathematical modeling of the dynamic storage of iron in ferritin

PubMed Central

2010-01-01

Background Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Results Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. Conclusions The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption. PMID:21047430

Mathematical modeling of the dynamic storage of iron in ferritin.

PubMed

Salgado, J Cristian; Olivera-Nappa, Alvaro; Gerdtzen, Ziomara P; Tapia, Victoria; Theil, Elizabeth C; Conca, Carlos; Nuñez, Marco T

2010-11-03

Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content. Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded. The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.

Diazo compounds for the bioreversible esterification of proteins† †Electronic supplementary information (ESI) available: Experimental procedures, analytical data, and spectral data for novel compounds. See DOI: 10.1039/c4sc01768d Click here for additional data file.

PubMed Central

McGrath, Nicholas A.; Andersen, Kristen A.; Davis, Amy K. F.; Lomax, Jo E.

2015-01-01

A diazo compound is shown to convert carboxylic acids to esters efficiently in an aqueous environment. The basicity of the diazo compound is critical: low basicity does not lead to a reaction but high basicity leads to hydrolysis. This reactivity extends to carboxylic acid groups in a protein. The ensuing esters are hydrolyzed by human cellular esterases to regenerate protein carboxyl groups. This new mode of chemical modification could enable the key advantages of prodrugs to be translated from small-molecules to proteins. PMID:25544883

Potential usage of proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of metastatic melanoma: basic and clinical aspects

PubMed Central

Shahshahan, Mohammad A; Beckley, Maureen N; Jazirehi, Ali R

2011-01-01

Protein degradation by proteasome is essential to the regulation of important cellular functions including cell cycle progression, proliferation, differentiation and apoptosis. Abnormal proteasomal degradation of key regulatory proteins perturbs the normal dynamics of these cellular processes culminating in uncontrolled cell cycle progression and decreased apoptosis leading to the characteristic cancer cell phenotype. Proteasome inhibitors are a novel group of therapeutic agents designed to oppose the increased proteasomal degradation observed in various cancers while restoring key cellular functions such as apoptosis, cell cycle progression, and the inhibition of angiogenesis. Several proteasome inhibitors have been evaluated in pre- and clinical studies for their potential usage in clinical oncology. Bortezomib (Velcade, PS-341) is the first Food and Drug Administration-approved proteasome inhibitor for the treatment of multiple myeloma and mantle cell lymphoma. Bortezomib's ability to preferentially induce toxicity and cell death in tumor cells while rendering healthy cells unaffected makes it a powerful therapeutic agent and has extended its use in other types of malignancies. The ability of bortezomib and other proteasome inhibitors to synergize with conventional therapies in killing tumors in various in vitro and in vivo models makes this class of drugs a powerful tool in overcoming acquired and inherent resistance observed in many cancers. This is achieved through modulation of aberrant cellular survival signal transduction pathways and their downstream anti-apoptotic gene products. This review will discuss the anti-neoplastic effects of various proteasome inhibitors in a variety of cancers with a special emphasis on bortezomib, its mechanism of action and role in cancer therapy. We further discuss the potential use of bortezomib in the treatment of metastatic melanoma. PMID:22016836

Off the shelf cellular therapeutics: Factors to consider during cryopreservation and storage of human cells for clinical use.

PubMed

Woods, Erik J; Thirumala, Sreedhar; Badhe-Buchanan, Sandhya S; Clarke, Dominic; Mathew, Aby J

2016-06-01

The field of cellular therapeutics has immense potential, affording an exciting array of applications in unmet medical needs. One of several key issues is an emphasis on getting these therapies from bench to bedside without compromising safety and efficacy. The successful commercialization of cellular therapeutics will require many to extend the shelf-life of these therapies beyond shipping "fresh" at ambient or chilled temperatures for "just in time" infusion. Cryopreservation is an attractive option and offers potential advantages, such as storing and retaining patient samples in case of a relapse, banking large quantities of allogeneic cells for broader distribution and use and retaining testing samples for leukocyte antigen typing and matching. However, cryopreservation is only useful if cells can be reanimated to physiological life with negligible loss of viability and functionality. Also critical is the logistics of storing, processing and transporting cells in clinically appropriate packaging systems and storage devices consistent with quality and regulatory standards. Rationalized approaches to develop commercial-scale cell therapies require an efficient cryopreservation system that provides the ability to inventory standardized products with maximized shelf life for later on-demand distribution and use, as well as a method that is scientifically sound and optimized for the cell of interest. The objective of this review is to bridge this gap between the basic science of cryobiology and its application in this context by identifying several key aspects of cryopreservation science in a format that may be easily integrated into mainstream cell therapy manufacture. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Classic Nuclear Localization Signals and a Novel Nuclear Localization Motif Are Required for Nuclear Transport of Porcine Parvovirus Capsid Proteins

PubMed Central

Boisvert, Maude; Bouchard-Lévesque, Véronique; Fernandes, Sandra

2014-01-01

ABSTRACT Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses. IMPORTANCE Most DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid protein (VP1) of porcine parvovirus. The major protein (VP2) nuclear localization was shown to depend on a complex structural motif. This motif can be used as a strategy by the virus to avoid transport of incorrectly folded proteins and to selectively import assembled trimers into the nucleus. Structural nuclear localization motifs can also be important for nuclear proteins without a classic basic amino acid stretch, including multimeric cellular proteins. PMID:25078698

[The mechanism of phenoptosis: I. Age-dependent decrease of the overall rate of protein synthesis is caused by the programmed attenuation of bio-energetics].

PubMed

Trubitsyn, A G

2009-01-01

The age-dependent degradation of all vital processes of an organism can be result of influences of destructive factors (the stochastic mechanism of aging), or effect of realizations of the genetic program (phenoptosis). The stochastic free-radical theory of aging dominating now contradicts the set of empirical data, and the semicentenial attempts to create the means to slow down aging did not give any practical results. It makes obvious that the stochastic mechanism of aging is incorrect. At the same time, the alternative mechanism of the programmed aging is not developed yet but preconditions for it development have already been created. It is shown that the genes controlling process of aging exist (contrary to the customary opinion) and the increase in the level of damaged macromolecules (basic postulate of the free-radical theory) can be explained by programmed attenuation of bio-energetics. As the bio-energetics is a driving force of all vital processes, decrease of its level is capable to cause degradation of all functions of an organism. However to transform this postulate into a basis of the theory of phenoptosis it is necessary to show, that attenuation of bio-energetics predetermines such fundamental processes accompanying aging as decrease of the overall rate of protein biosynthesis, restriction of cellular proliferations (Hayflick limit), loss of telomeres etc. This article is the first step in this direction: the natural mechanism of interaction of overall rate of protein synthesis with a level of cellular bio-energetics is shown. This is built-in into the translation machine and based on dependence of recirculation rate of eukaryotic initiation factor 2 (elF2) from ATP/ADP value that is created by mitochondrial bio-energetic machine.

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction.

PubMed

Podlasek, Carol A; Mulhall, John; Davies, Kelvin; Wingard, Christopher J; Hannan, Johanna L; Bivalacqua, Trinity J; Musicki, Biljana; Khera, Mohit; González-Cadavid, Nestor F; Burnett, Arthur L

2016-08-01

The biological importance of testosterone is generally accepted by the medical community; however, controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. To provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Testosterone plays an important role in sexual function through multiple processes: physiologic (stimulates activity of nitric oxide synthase), developmental (establishes and maintains the structural and functional integrity of the penis), neural (development, maintenance, function, and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes, and prostatectomy), and phosphodiesterase type 5 inhibition (testosterone supplement to counteract phosphodiesterase type 5 inhibitor resistance). Despite controversies concerning testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction. Published by Elsevier Inc.

Endocytosis of glycosylphosphatidylinositol-anchored proteins

PubMed Central

2009-01-01

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) represent an interesting amalgamation of the three basic kinds of cellular macromolecules viz. proteins, carbohydrates and lipids. An unusually hybrid moiety, the GPI-anchor is expressed in a diverse range of organisms from parasites to mammalian cells and serves to anchor a large number of functionally diverse proteins and has been the center of attention in scientific debate for some time now. Membrane organization of GPI-APs into laterally-organized cholesterol-sphingolipid ordered membrane domains or "rafts" and endocytosis of GPI-APs has been intensely debated. Inclusion into or exclusion from these membrane domains seems to be the critical factor in determining the endocytic mechanisms and intracellular destinations of GPI-APs. The intracellular signaling as well as endocytic trafficking of GPI-APs is critically dependent upon the cell surface organization of GPI-APs, and the associations with these lipid rafts play a vital role during these processes. The mechanism of endocytosis for GPI-APs may differ from other cellular endocytic pathways, such as those mediated by clathrin-coated pits (caveolae), and is necessary for unique biological functions. Numerous intracellular factors are involved in and regulate the endocytosis of GPI-APs, and these may be variably dependent on cell-type. The central focus of this article is to describe the significance of the endocytosis of GPI-APs on a multitude of biological processes, ranging from nutrient-uptake to more complex immune responses. Ultimately, a thorough elucidation of GPI-AP mediated signaling pathways and their regulatory elements will enhance our understanding of essential biological processes and benefit as components of disease intervention strategies. PMID:19832981

San Diego field operational test of smart call boxes : technical aspects

DOT National Transportation Integrated Search

1997-01-01

Smart call boxes are devices similar to those used as emergency call boxes in California. The basic call box consists of a microprocessor, a cellular transceiver, and a solar power source. The smart call box system also includes data-collection devic...

Mobile Computing and Ubiquitous Networking: Concepts, Technologies and Challenges.

ERIC Educational Resources Information Center

Pierre, Samuel

2001-01-01

Analyzes concepts, technologies and challenges related to mobile computing and networking. Defines basic concepts of cellular systems. Describes the evolution of wireless technologies that constitute the foundations of mobile computing and ubiquitous networking. Presents characterization and issues of mobile computing. Analyzes economical and…

Effects of environmental pollutants on cellular iron homeostasis and ultimate links to human disease

EPA Science Inventory

Chronic disease has increased in the last several decades, and environmental pollutants have been implicated. The magnitude and variety of diseases indicate the malfunctioning of some basic mechanism underlying human health. Environmental pollutants demonstrate a capability to co...

Implementation of Basic and Universal Gates In a single Circuit Based On Quantum-dot Cellular Automata Using Multi-Layer Crossbar Wire

NASA Astrophysics Data System (ADS)

Bhowmik, Dhrubajyoti; Saha, Apu Kr; Dutta, Paramartha; Nandi, Supratim

2017-08-01

Quantum-dot Cellular Automata (QCA) is one of the most substitutes developing nanotechnologies for electronic circuits, as a result of lower force utilization, higher speed and smaller size in correlation with CMOS innovation. The essential devices, a Quantum-dot cell can be utilized to logic gates and wires. As it is the key building block on nanotechnology circuits. By applying simple gates, the hardware requirements for a QCA circuit can be decreased and circuits can be less complex as far as level, delay and cell check. This article exhibits an unobtrusive methodology for actualizing novel upgraded simple and universal gates, which can be connected to outline numerous variations of complex QCA circuits. Proposed gates are straightforward in structure and capable as far as implementing any digital circuits. The main aim is to build all basic and universal gates in a simple circuit with and without crossbar-wire. Simulation results and physical relations affirm its handiness in actualizing each advanced circuit.

On the phase space structure of IP3 induced Ca2+ signalling and concepts for predictive modeling

NASA Astrophysics Data System (ADS)

Falcke, Martin; Moein, Mahsa; TilÅ«naitÄ--, Agne; Thul, Rüdiger; Skupin, Alexander

2018-04-01

The correspondence between mathematical structures and experimental systems is the basis of the generalizability of results found with specific systems and is the basis of the predictive power of theoretical physics. While physicists have confidence in this correspondence, it is less recognized in cellular biophysics. On the one hand, the complex organization of cellular dynamics involving a plethora of interacting molecules and the basic observation of cell variability seem to question its possibility. The practical difficulties of deriving the equations describing cellular behaviour from first principles support these doubts. On the other hand, ignoring such a correspondence would severely limit the possibility of predictive quantitative theory in biophysics. Additionally, the existence of functional modules (like pathways) across cell types suggests also the existence of mathematical structures with comparable universality. Only a few cellular systems have been sufficiently investigated in a variety of cell types to follow up these basic questions. IP3 induced Ca2+signalling is one of them, and the mathematical structure corresponding to it is subject of ongoing discussion. We review the system's general properties observed in a variety of cell types. They are captured by a reaction diffusion system. We discuss the phase space structure of its local dynamics. The spiking regime corresponds to noisy excitability. Models focussing on different aspects can be derived starting from this phase space structure. We discuss how the initial assumptions on the set of stochastic variables and phase space structure shape the predictions of parameter dependencies of the mathematical models resulting from the derivation.

Engineering self-contained DNA circuit for proximity recognition and localized signal amplification of target biomolecules

PubMed Central

Ang, Yan Shan; Yung, Lin-Yue Lanry

2014-01-01

Biomolecular interactions have important cellular implications, however, a simple method for the sensing of such proximal events is lacking in the current molecular toolbox. We designed a dynamic DNA circuit capable of recognizing targets in close proximity to initiate a pre-programmed signal transduction process resulting in localized signal amplification. The entire circuit was engineered to be self-contained, i.e. it can self-assemble onto individual target molecules autonomously and form localized signal with minimal cross-talk. α-thrombin was used as a model protein to evaluate the performance of the individual modules and the overall circuit for proximity interaction under physiologically relevant buffer condition. The circuit achieved good selectivity in presence of non-specific protein and interfering serum matrix and successfully detected for physiologically relevant α-thrombin concentration (50 nM–5 μM) in a single mixing step without any further washing. The formation of localized signal at the interaction site can be enhanced kinetically through the control of temperature and probe concentration. This work provides a basic general framework from which other circuit modules can be adapted for the sensing of other biomolecular or cellular interaction of interest. PMID:25056307

Strolling Toward New Concepts.

PubMed

Ito, Koreaki

2016-09-08

For more than four decades now, I have been studying how genetic information is transformed into protein-based cellular functions. This has included investigations into the mechanisms supporting cellular localization of proteins, disulfide bond formation, quality control of membranes, and translation. I tried to extract new principles and concepts that are universal among living organisms from our observations of Escherichia coli. While I wanted to distill complex phenomena into basic principles, I also tried not to overlook any serendipitous observations. In the first part of this article, I describe personal experiences during my studies of the Sec pathway, which have centered on the SecY translocon. In the second part, I summarize my views of the recent revival of translation studies, which has given rise to the concept that nonuniform polypeptide chain elongation is relevant for the subsequent fates of newly synthesized proteins. Our studies of a class of regulatory nascent polypeptides advance this concept by showing that the dynamic behaviors of the extraribosomal part of the nascent chain affect the ongoing translation process. Vibrant and regulated molecular interactions involving the ribosome, mRNA, and nascent polypeptidyl-tRNA are based, at least partly, on their autonomously interacting properties.

Mitral valve disease—morphology and mechanisms

PubMed Central

Levine, Robert A.; Hagége, Albert A.; Judge, Daniel P.; Padala, Muralidhar; Dal-Bianco, Jacob P.; Aikawa, Elena; Beaudoin, Jonathan; Bischoff, Joyce; Bouatia-Naji, Nabila; Bruneval, Patrick; Butcher, Jonathan T.; Carpentier, Alain; Chaput, Miguel; Chester, Adrian H.; Clusel, Catherine; Delling, Francesca N.; Dietz, Harry C.; Dina, Christian; Durst, Ronen; Fernandez-Friera, Leticia; Handschumacher, Mark D.; Jensen, Morten O.; Jeunemaitre, Xavier P.; Le Marec, Hervé; Le Tourneau, Thierry; Markwald, Roger R.; Mérot, Jean; Messas, Emmanuel; Milan, David P.; Neri, Tui; Norris, Russell A.; Peal, David; Perrocheau, Maelle; Probst, Vincent; Pucéat, Michael; Rosenthal, Nadia; Solis, Jorge; Schott, Jean-Jacques; Schwammenthal, Ehud; Slaugenhaupt, Susan A.; Song, Jae-Kwan; Yacoub, Magdi H.

2016-01-01

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but—even in adult life—remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular–ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease. PMID:26483167

Studying Mechanosensitivity of Two-Pore Domain K+ Channels in Cellular and Reconstituted Proteoliposome Membranes.

PubMed

Del Mármol, Josefina; Rietmeijer, Robert A; Brohawn, Stephen G

2018-01-01

Mechanical force sensation is fundamental to a wide breadth of biology from the classic senses of touch, pain, hearing, and balance to less conspicuous sensations of proprioception, blood pressure, and osmolarity and basic aspects of cell growth, differentiation, and development. These diverse and essential systems use force-gated (or mechanosensitive) ion channels that convert mechanical stimuli into cellular electrical signals. TRAAK, TREK1, and TREK2 are K + -selective ion channels of the two-pore domain K + (K2P) family that are mechanosensitive: they are gated open by increasing membrane tension. TRAAK and TREK channels are thought to play roles in somatosensory and other mechanosensory processes in neuronal and non-neuronal tissues. Here, we present protocols for three assays to study mechanical activation of these channels in cell membranes: (1) cell swelling, (2) cell poking, and (3) patched membrane stretching. Patched membrane stretching is also applicable to the study of mechanosensitive K2P channel activity in a cell-free system and a procedure for proteoliposome reconstitution and patching is also presented. These approaches are also readily applicable to the study of other mechanosensitive ion channels.

Next-generation mammalian genetics toward organism-level systems biology.

PubMed

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

Genomic Pangea: coordinate gene regulation and cell-specific chromosomal topologies.

PubMed

Laster, Kyle; Kosak, Steven T

2010-06-01

The eukaryotic nucleus is functionally organized. Gene loci, for example, often reveal altered localization patterns according to their developmental regulation. Whole chromosomes also demonstrate non-random nuclear positions, correlated with inherent characteristics such as gene density or size. Given that hundreds to thousands of genes are coordinately regulated in any given cell type, interest has grown in whether chromosomes may be specifically localized according to gene regulation. A synthesis of the evidence for preferential chromosomal organization suggests that, beyond basic characteristics, chromosomes can assume positions functionally related to gene expression. Moreover, analysis of total chromosome organization during cellular differentiation indicates that unique chromosome topologies, albeit probabilistic, in effect define a cell lineage. Future work with new techniques, including the advanced forms of the chromosome conformation capture (3C), and the development of next-generation whole-genome imaging approaches, will help to refine our view of chromosomal organization. We suggest that genomic organization during cellular differentiation should be viewed as a dynamic process, with gene expression patterns leading to chromosome associations that feed back on themselves, leading to the self-organization of the genome according to coordinate gene regulation. Copyright 2010 Elsevier Ltd. All rights reserved.

Competent for commitment: you've got to have heart!

PubMed

Jain, Rajan; Epstein, Jonathan A

2018-01-01

The mature heart is composed primarily of four different cell types: cardiac myocytes, endothelium, smooth muscle, and fibroblasts. These cell types derive from pluripotent progenitors that become progressively restricted with regard to lineage potential, giving rise to multipotent cardiac progenitor cells and, ultimately, the differentiated cell types of the heart. Recent studies have begun to shed light on the defining characteristics of the intermediary cell types that exist transiently during this developmental process and the extrinsic and cell-autonomous factors that influence cardiac lineage decisions and cellular competence. This information will shape our understanding of congenital and adult cardiac disease and guide regenerative therapeutic approaches. In addition, cardiac progenitor specification can serve as a model for understanding basic mechanisms regulating the acquisition of cellular identity. In this review, we present the concept of "chromatin competence" that describes the potential for three-dimensional chromatin organization to function as the molecular underpinning of the ability of a progenitor cell to respond to inductive lineage cues and summarize recent studies advancing our understanding of cardiac cell specification, gene regulation, and chromatin organization and how they impact cardiac development. © 2018 Jain and Epstein; Published by Cold Spring Harbor Laboratory Press.

The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses.

PubMed

Haigh, Cathryn L; Tumpach, Carolin; Drew, Simon C; Collins, Steven J

2015-01-01

Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments have been shown to bind to anionic phospholipids at low pH. We sought to investigate binding with other lipid moieties and queried how such interactions could be relevant to the cellular functions of these fragments. Both N1 and N2 bound phosphatidylserine (PS), as previously reported, and a further interaction with phosphatidic acid (PA) was also identified. The specificity of this interaction required the N-terminus, especially the proline motif within the basic amino acids at the N-terminus, together with the copper-binding region (unrelated to copper saturation). Previously, the fragments have been shown to be protective against cellular stresses. In the current study, serum deprivation was used to induce changes in the cellular lipid environment, including externalisation of plasma membrane PS and increased cellular levels of PA. When copper-saturated, N2 could reverse these changes, but N1 could not, suggesting that direct binding of N2 to cellular lipids may be part of the mechanism by which this peptide signals its protective response.

The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses

PubMed Central

Haigh, Cathryn L.; Tumpach, Carolin; Drew, Simon C.; Collins, Steven J.

2015-01-01

Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments have been shown to bind to anionic phospholipids at low pH. We sought to investigate binding with other lipid moieties and queried how such interactions could be relevant to the cellular functions of these fragments. Both N1 and N2 bound phosphatidylserine (PS), as previously reported, and a further interaction with phosphatidic acid (PA) was also identified. The specificity of this interaction required the N-terminus, especially the proline motif within the basic amino acids at the N-terminus, together with the copper-binding region (unrelated to copper saturation). Previously, the fragments have been shown to be protective against cellular stresses. In the current study, serum deprivation was used to induce changes in the cellular lipid environment, including externalisation of plasma membrane PS and increased cellular levels of PA. When copper-saturated, N2 could reverse these changes, but N1 could not, suggesting that direct binding of N2 to cellular lipids may be part of the mechanism by which this peptide signals its protective response. PMID:26252007

The Neurolab mission and biomedical engineering: a partnership for the future.

PubMed

Liskowsky, D R; Frey, M A; Sulzman, F M; White, R J; Likowsky, D R

1996-01-01

Over the last five years, with the advent of flights of U.S. Shuttle/Spacelab missions dedicated entirely to life sciences research, the opportunities for conducting serious studies that use a fully outfitted space laboratory to better understand basic biological processes have increased. The last of this series of Shuttle/Spacelab missions, currently scheduled for 1998, is dedicated entirely to neuroscience and behavioral research. The mission, named Neurolab, includes a broad range of experiments that build on previous research efforts, as well as studies related to less mature areas of space neuroscience. The Neurolab mission provides the global scientific community with the opportunity to use the space environment for investigations that exploit microgravity to increase our understanding of basic processes in neuroscience. The results from this premier mission should lead to a significant advancement in the field as a whole and to the opening of new lines of investigation for future research. Experiments under development for this mission will utilize human subjects as well as a variety of other species. The capacity to carry out detailed experiments on both human and animal subjects in space allows a diverse complement of studies that investigate functional changes and their underlying molecular, cellular, and physiological mechanisms. In order to conduct these experiments, a wide array of biomedical instrumentation will be used, including some instruments and devices being developed especially for the mission.

The Neurolab mission and biomedical engineering: a partnership for the future

NASA Technical Reports Server (NTRS)

Liskowsky, D. R.; Frey, M. A.; Sulzman, F. M.; White, R. J.; Likowsky, D. R.

1996-01-01

Over the last five years, with the advent of flights of U.S. Shuttle/Spacelab missions dedicated entirely to life sciences research, the opportunities for conducting serious studies that use a fully outfitted space laboratory to better understand basic biological processes have increased. The last of this series of Shuttle/Spacelab missions, currently scheduled for 1998, is dedicated entirely to neuroscience and behavioral research. The mission, named Neurolab, includes a broad range of experiments that build on previous research efforts, as well as studies related to less mature areas of space neuroscience. The Neurolab mission provides the global scientific community with the opportunity to use the space environment for investigations that exploit microgravity to increase our understanding of basic processes in neuroscience. The results from this premier mission should lead to a significant advancement in the field as a whole and to the opening of new lines of investigation for future research. Experiments under development for this mission will utilize human subjects as well as a variety of other species. The capacity to carry out detailed experiments on both human and animal subjects in space allows a diverse complement of studies that investigate functional changes and their underlying molecular, cellular, and physiological mechanisms. In order to conduct these experiments, a wide array of biomedical instrumentation will be used, including some instruments and devices being developed especially for the mission.

Localization and phosphorylation of Plasmodium falciparum nicotinamide/nicotinate mononucleotide adenylyltransferase (PfNMNAT) in intraerythrocytic stages.

PubMed

Nieto, Carlos A; Sánchez, Lina M; Sánchez, Diana M; Díaz, Gonzalo J; Ramírez, María H

2018-04-11

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in the energy metabolism of living beings, and it has various cellular functions. The main enzyme in the biosynthesis of this nucleotide is nicotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1/18) because it is the convergence point for all known biosynthetic pathways. NMNATs have divergences in both the number of isoforms detected and their distribution, depending on the organism. In the laboratory of basic research in biochemistry (LIBBIQ: acronym in Spanish) the NMNATs of protozoan parasites (Leishmania braziliensis, Plasmodium falciparum, Trypanosoma cruzi, and Giardia duodenalis) have been studied, analysing their catalytic properties through the use of proteins. Recombinants and their cellular distribution essentially. In 2014, O'Hara et al. determined the cytoplasmic localization of NMNAT of P. falciparum, using a transgene coupled to GFP, however, the addition of labels to the study protein can modify several of its characteristics, including its sub-cellular localization. This study confirms the cytoplasmic localization of this protein in the parasite through recognition of the endogenous protein in the different stages of the asexual life cycle. Additionally, the study found that PfNMNAT could be a phosphorylation target at serine, tyrosine and threonine residues, and it shows variations during the asexual life cycle. These experiments confirmed that the parasite is situated in the cytoplasm, fulfilling the required functions of NAD+ in this compartment, the PfNMNAT is regulated in post-transcription processes, and can be regulated by phosphorylation in its residues.

Mapping Cellular Polarity Networks Using Mass Spectrometry-based Strategies.

PubMed

Daulat, Avais M; Puvirajesinghe, Tania M; Camoin, Luc; Borg, Jean-Paul

2018-05-18

Cell polarity is a vital biological process involved in the building, maintenance and normal functioning of tissues in invertebrates and vertebrates. Unsurprisingly, molecular defects affecting polarity organization and functions have a strong impact on tissue homeostasis, embryonic development and adult life, and may directly or indirectly lead to diseases. Genetic studies have demonstrated the causative effect of several polarity genes in diseases; however, much remains to be clarified before a comprehensive view of the molecular organization and regulation of the protein networks associated with polarity proteins is obtained. This challenge can be approached head-on using proteomics to identify protein complexes involved in cell polarity and their modifications in a spatio-temporal manner. We review the fundamental basics of mass spectrometry techniques and provide an in-depth analysis of how mass spectrometry has been instrumental in understanding the complex and dynamic nature of some cell polarity networks at the tissue (apico-basal and planar cell polarities) and cellular (cell migration, ciliogenesis) levels, with the fine dissection of the interconnections between prototypic cell polarity proteins and signal transduction cascades in normal and pathological situations. This review primarily focuses on epithelial structures which are the fundamental building blocks for most metazoan tissues, used as the archetypal model to study cellular polarity. This field offers broad perspectives thanks to the ever-increasing sensitivity of mass spectrometry and its use in combination with recently developed molecular strategies able to probe in situ proteomic networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Altered cell function in microgravity

NASA Technical Reports Server (NTRS)

Hughes-Fulford, Millie

1991-01-01

The paper overviews published results from investigations of changes in basic biological parameters taking place as a result of spaceflight exposure. These include changes in the rates of the DNA, mRNA, and protein biosyntheses; changes in the growth rate of an organism; and alterations in the cytoskeleton structure, differentiation, hormone accumulation, and collagen matrix secretion. These results, obtained both in complex biological organisms and on cultured cells, suggest that a basic cellular function is influenced and changed by microgravity. Many of the above mentioned changes are also found to take place in aging cells.

Failover in Cellular Automata

NASA Astrophysics Data System (ADS)

Kumar, Shailesh; Rao, Shrisha

This paper studies a phenomenon called failover, and shows that this phenomenon (in particular, stateless failover) can be modeled by Game of Life cellular automata. This is the first time that this sophisticated real-life system behavior has been modeled in abstract terms. A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using the primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009.

PubMed

Harman, Denham

2009-12-01

Aging is the progressive accumulation in an organism of diverse, deleterious changes with time that increase the chance of disease and death. The basic chemical process underlying aging was first advanced by the free radical theory of aging (FRTA) in 1954: the reaction of active free radicals, normally produced in the organisms, with cellular constituents initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life. The initial low acceptance of the FRTA by the scientific community, its slow growth, manifested by meetings and occasional papers based on the theory, prompted this account of the intermittent growth of acceptance of the theory over the past nearly 55 years.

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Optical and force nanoscopy in microbiology.

PubMed

Xiao, Jie; Dufrêne, Yves F

2016-10-26

Microbial cells have developed sophisticated multicomponent structures and machineries to govern basic cellular processes, such as chromosome segregation, gene expression, cell division, mechanosensing, cell adhesion and biofilm formation. Because of the small cell sizes, subcellular structures have long been difficult to visualize using diffraction-limited light microscopy. During the last three decades, optical and force nanoscopy techniques have been developed to probe intracellular and extracellular structures with unprecedented resolutions, enabling researchers to study their organization, dynamics and interactions in individual cells, at the single-molecule level, from the inside out, and all the way up to cell-cell interactions in microbial communities. In this Review, we discuss the principles, advantages and limitations of the main optical and force nanoscopy techniques available in microbiology, and we highlight some outstanding questions that these new tools may help to answer.

Fournier's gangrene of the penis in a 12-year-old patient secondary to phimosis.

PubMed

Ward, Luther; Eisenson, Daniel; Fils, Jean-Louis

2016-12-01

We report a case of Fournier's gangrene in a 12-year-old boy from St. Boniface Hospital in Fond-des-Blancs, Haiti. Fournier's gangrene, a fulminant necrotizing fasciitis of the penis and scrotum, is a rare and life-threatening infection that requires hospitalization, broad-spectrum antibiotics, and surgical debridement.1-3 It is usually associated with impaired cellular immunity due to systemic disorders such as diabetes and liver disease.4,5 This patient had none of those risk factors, but had severe, longstanding phimosis, for which circumcision had been recommended many years before. This case illustrates how lack of access to basic surgical care for an easily treatable condition leads to advanced presentation of a severe disease process. [Full article available at http://rimed.org/rimedicaljournal-2016-12.asp].

Precision medicine for psychopharmacology: a general introduction.

PubMed

Shin, Cheolmin; Han, Changsu; Pae, Chi-Un; Patkar, Ashwin A

2016-07-01

Precision medicine is an emerging medical model that can provide accurate diagnoses and tailored therapeutic strategies for patients based on data pertaining to genes, microbiomes, environment, family history and lifestyle. Here, we provide basic information about precision medicine and newly introduced concepts, such as the precision medicine ecosystem and big data processing, and omics technologies including pharmacogenomics, pharamacometabolomics, pharmacoproteomics, pharmacoepigenomics, connectomics and exposomics. The authors review the current state of omics in psychiatry and the future direction of psychopharmacology as it moves towards precision medicine. Expert commentary: Advances in precision medicine have been facilitated by achievements in multiple fields, including large-scale biological databases, powerful methods for characterizing patients (such as genomics, proteomics, metabolomics, diverse cellular assays, and even social networks and mobile health technologies), and computer-based tools for analyzing large amounts of data.

Topical oxygenation therapy in wound care: are patients getting enough?

PubMed

Hunt, Sharon

2017-08-10

Wound management is a major burden on today's healthcare provider, both clinically with regard to available resources and financially. Most importantly, it has a significant impact on the patient's quality of life and experience. Within the field of wound care these pressures, alongside an ageing population, multiple comorbidities, disease processes and negative lifestyle choices, increase incidences of reduced skin integrity and challenging wounds. In an attempt to meet these challenges alternative, innovative therapies are being explored to support the wound healing process. Wound care experts are now exploring the scientific, biological aspects of wound healing at a cellular level. They are taking wound care back to basics with the identification of elements that, if introduced as an 'adjunct' or as a stand-alone device alongside gold-standard regimens, can positively impact the static or problematic wounds that pose the most challenges to clinicians on a daily basis. This article explores the phenomenon of oxygen, its place in tissue formation and the effect of depletion on the wound healing process and highlights ways in which patients may receive benefit from non-invasive intervention to improve wound care outcomes.

The bioelectric code: An ancient computational medium for dynamic control of growth and form.

PubMed

Levin, Michael; Martyniuk, Christopher J

2018-02-01

What determines large-scale anatomy? DNA does not directly specify geometrical arrangements of tissues and organs, and a process of encoding and decoding for morphogenesis is required. Moreover, many species can regenerate and remodel their structure despite drastic injury. The ability to obtain the correct target morphology from a diversity of initial conditions reveals that the morphogenetic code implements a rich system of pattern-homeostatic processes. Here, we describe an important mechanism by which cellular networks implement pattern regulation and plasticity: bioelectricity. All cells, not only nerves and muscles, produce and sense electrical signals; in vivo, these processes form bioelectric circuits that harness individual cell behaviors toward specific anatomical endpoints. We review emerging progress in reading and re-writing anatomical information encoded in bioelectrical states, and discuss the approaches to this problem from the perspectives of information theory, dynamical systems, and computational neuroscience. Cracking the bioelectric code will enable much-improved control over biological patterning, advancing basic evolutionary developmental biology as well as enabling numerous applications in regenerative medicine and synthetic bioengineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic pathway modeling of signal transduction networks: a domain-oriented approach.

PubMed

Conzelmann, Holger; Gilles, Ernst-Dieter

2008-01-01

Mathematical models of biological processes become more and more important in biology. The aim is a holistic understanding of how processes such as cellular communication, cell division, regulation, homeostasis, or adaptation work, how they are regulated, and how they react to perturbations. The great complexity of most of these processes necessitates the generation of mathematical models in order to address these questions. In this chapter we provide an introduction to basic principles of dynamic modeling and highlight both problems and chances of dynamic modeling in biology. The main focus will be on modeling of s transduction pathways, which requires the application of a special modeling approach. A common pattern, especially in eukaryotic signaling systems, is the formation of multi protein signaling complexes. Even for a small number of interacting proteins the number of distinguishable molecular species can be extremely high. This combinatorial complexity is due to the great number of distinct binding domains of many receptors and scaffold proteins involved in signal transduction. However, these problems can be overcome using a new domain-oriented modeling approach, which makes it possible to handle complex and branched signaling pathways.

Imaging Cell Shape Change in Living Drosophila Embryos

PubMed Central

Figard, Lauren; Sokac, Anna Marie

2011-01-01

The developing Drosophila melanogaster embryo undergoes a number of cell shape changes that are highly amenable to live confocal imaging. Cell shape changes in the fly are analogous to those in higher organisms, and they drive tissue morphogenesis. So, in many cases, their study has direct implications for understanding human disease (Table 1)1-5. On the sub-cellular scale, these cell shape changes are the product of activities ranging from gene expression to signal transduction, cell polarity, cytoskeletal remodeling and membrane trafficking. Thus, the Drosophila embryo provides not only the context to evaluate cell shape changes as they relate to tissue morphogenesis, but also offers a completely physiological environment to study the sub-cellular activities that shape cells. The protocol described here is designed to image a specific cell shape change called cellularization. Cellularization is a process of dramatic plasma membrane growth, and it ultimately converts the syncytial embryo into the cellular blastoderm. That is, at interphase of mitotic cycle 14, the plasma membrane simultaneously invaginates around each of ~6000 cortically anchored nuclei to generate a sheet of primary epithelial cells. Counter to previous suggestions, cellularization is not driven by Myosin-2 contractility6, but is instead fueled largely by exocytosis of membrane from internal stores7. Thus, cellularization is an excellent system for studying membrane trafficking during cell shape changes that require plasma membrane invagination or expansion, such as cytokinesis or transverse-tubule (T-tubule) morphogenesis in muscle. Note that this protocol is easily applied to the imaging of other cell shape changes in the fly embryo, and only requires slight adaptations such as changing the stage of embryo collection, or using "embryo glue" to mount the embryo in a specific orientation (Table 1)8-19. In all cases, the workflow is basically the same (Figure 1). Standard methods for cloning and Drosophila transgenesis are used to prepare stable fly stocks that express a protein of interest, fused to Green Fluorescent Protein (GFP) or its variants, and these flies provide a renewable source of embryos. Alternatively, fluorescent proteins/probes are directly introduced into fly embryos via straightforward micro-injection techniques9-10. Then, depending on the developmental event and cell shape change to be imaged, embryos are collected and staged by morphology on a dissecting microscope, and finally positioned and mounted for time-lapse imaging on a confocal microscope. PMID:21490577

C-Terminal Clipping of Chemokine CCL1/I-309 Enhances CCR8-Mediated Intracellular Calcium Release and Anti-Apoptotic Activity

PubMed Central

Denis, Catherine; Deiteren, Kathleen; Mortier, Anneleen; Tounsi, Amel; Fransen, Erik; Proost, Paul; Renauld, Jean-Christophe; Lambeir, Anne-Marie

2012-01-01

Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease in inflammatory environments. Since the function of CPM in and beyond inflammation remains mainly undefined, the identification of natural substrates can aid in discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C-terminal basic amino acids, forms a potential natural substrate for CPM. CCL1 plays a role not only in inflammation but also in apoptosis, angiogenesis and tumor biology. Enzymatic processing differently impacts the biological activity of chemokines thereby contributing to the complex regulation of the chemokine system. The aim of the present study was to investigate whether (i) CCL1/I-309 is prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered after C-terminal proteolytic processing. CCL1 was identified as a novel substrate for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to CCR8. In line with the higher intracellular calcium release, a pronounced increase of the anti-apoptotic activity of CCL1 was observed in the BW5147 cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study suggest that CPM is a likely candidate for the regulation of biological processes relying on the CCL1-CCR8 system. PMID:22479563

Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

PubMed Central

2009-01-01

Background The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes. Results We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality. Conclusion We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing essentiality. PMID:19758426

Oxygen regulates molecular mechanisms of cancer progression and metastasis.

PubMed

Gupta, Kartik; Madan, Esha; Sayyid, Muzzammil; Arias-Pulido, Hugo; Moreno, Eduardo; Kuppusamy, Periannan; Gogna, Rajan

2014-03-01

Oxygen is the basic molecule which supports life and it truly is "god's gift to life." Despite its immense importance, research on "oxygen biology" has never received the light of the day and has been limited to physiological and biochemical studies. It seems that in modern day biology, oxygen research is summarized in one word "hypoxia." Scientists have focused on hypoxia-induced transcriptomics and molecular-cellular alterations exclusively in disease models. Interestingly, the potential of oxygen to control the basic principles of biology like homeostatic maintenance, transcription, replication, and protein folding among many others, at the molecular level, has been completely ignored. Here, we present a perspective on the crucial role played by oxygen in regulation of basic biological phenomena. Our conclusion highlights the importance of establishing novel research areas like oxygen biology, as there is great potential in this field for basic science discoveries and clinical benefits to the society.

Teaching Cell Anatomy with a Fabric Model

ERIC Educational Resources Information Center

Kluka, Michelle

2005-01-01

Middle schoolers are often first introduced to detailed cellular anatomy through one-dimensional drawings in basic life science books, fill-in-the blank handouts accompanied by notes from the teacher, or desktop hard-plastic commercial models that resemble giant lollipops. One of the most important, yet difficult, life science concepts for…

PHARMAVIRTUA: Educational Software for Teaching and Learning Basic Pharmacology

ERIC Educational Resources Information Center

Fidalgo-Neto, Antonio Augusto; Alberto, Anael Viana Pinto; Bonavita, André Gustavo Calvano; Bezerra, Rômulo José Soares; Berçot, Felipe Faria; Lopes, Renato Matos; Alves, Luiz Anastacio

2014-01-01

Information and communication technologies have become important tools for teaching scientific subjects such as anatomy and histology as well as other, nondescriptive subjects like physiology and pharmacology. Software has been used to facilitate the learning of specific concepts at the cellular and molecular levels in the biological and health…

Biologically Predisposed Learning and Selective Associations in Amygdalar Neurons

ERIC Educational Resources Information Center

Chung, Ain; Barot, Sabiha K.; Kim, Jeansok J.; Bernstein, Ilene L.

2011-01-01

Modern views on learning and memory accept the notion of biological constraints--that the formation of association is not uniform across all stimuli. Yet cellular evidence of the encoding of selective associations is lacking. Here, conditioned stimuli (CSs) and unconditioned stimuli (USs) commonly employed in two basic associative learning…

Tomato Male sterile 1035 is essential for pollen development and meiosis in anthers

PubMed Central

Jeong, Hee-Jin; Kang, Jin-Ho; Zhao, Meiai; Kwon, Jin-Kyung; Choi, Hak-Soon; Bae, Jung Hwan; Lee, Hyun-ah; Joung, Young-Hee; Choi, Doil; Kang, Byoung-Cheorl

2014-01-01

Male fertility in flowering plants depends on proper cellular differentiation in anthers. Meiosis and tapetum development are particularly important processes in pollen production. In this study, we showed that the tomato male sterile (ms10 35) mutant of cultivated tomato (Solanum lycopersicum) exhibited dysfunctional meiosis and an abnormal tapetum during anther development, resulting in no pollen production. We demonstrated that Ms10 35 encodes a basic helix–loop–helix transcription factor that is specifically expressed in meiocyte and tapetal tissue from pre-meiotic to tetrad stages. Transgenic expression of the Ms10 35 gene from its native promoter complemented the male sterility of the ms10 35 mutant. In addition, RNA-sequencing-based transcriptome analysis revealed that Ms10 35 regulates 246 genes involved in anther development processes such as meiosis, tapetum development, cell-wall degradation, pollen wall formation, transport, and lipid metabolism. Our results indicate that Ms10 35 plays key roles in regulating both meiosis and programmed cell death of the tapetum during microsporogenesis. PMID:25262227

Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes

PubMed Central

Liepe, Juliane; Holzhütter, Hermann-Georg; Bellavista, Elena; Kloetzel, Peter M; Stumpf, Michael PH; Mishto, Michele

2015-01-01

Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predicted by the model, and experimentally supported. The analysis suggests that the rate-limiting step of hydrolysis is the transport of the substrates into the proteasome. The transport efficiency varies between human standard- and immuno-proteasomes thereby impinging upon total degradation rate and substrate cleavage-site usage. DOI: http://dx.doi.org/10.7554/eLife.07545.001 PMID:26393687

High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments.

PubMed

Soleilhac, Emmanuelle; Nadon, Robert; Lafanechere, Laurence

2010-02-01

Screening compounds with cell-based assays and microscopy image-based analysis is an approach currently favored for drug discovery. Because of its high information yield, the strategy is called high-content screening (HCS). This review covers the application of HCS in drug discovery and also in basic research of potential new pathways that can be targeted for treatment of pathophysiological diseases. HCS faces several challenges, however, including the extraction of pertinent information from the massive amount of data generated from images. Several proposed approaches to HCS data acquisition and analysis are reviewed. Different solutions from the fields of mathematics, bioinformatics and biotechnology are presented. Potential applications and limits of these recent technical developments are also discussed. HCS is a multidisciplinary and multistep approach for understanding the effects of compounds on biological processes at the cellular level. Reliable results depend on the quality of the overall process and require strong interdisciplinary collaborations.

Estrogen and the female heart.

PubMed

Knowlton, A A; Korzick, D H

2014-05-25

Estrogen has a plethora of effects in the cardiovascular system. Studies of estrogen and the heart span human clinical trials and basic cell and molecular investigations. Greater understanding of cell and molecular responses to estrogens can provide further insights into the findings of clinical studies. Differences in expression and cellular/intracellular distribution of the two main receptors, estrogen receptor (ER) α and β, are thought to account for the specificity and differences in responses to estrogen. Much remains to be learned in this area, but cellular distribution within the cardiovascular system is becoming clearer. Identification of GPER as a third ER has introduced further complexity to the system. 17β-estradiol (E2), the most potent human estrogen, clearly has protective properties activating a signaling cascade leading to cellular protection and also influencing expression of the protective heat shock proteins (HSP). E2 protects the heart from ischemic injury in basic studies, but the picture is more involved in the whole organism and clinical studies. Here the complexity of E2's widespread effects comes into play and makes interpretation of findings more challenging. Estrogen loss occurs primarily with aging, but few studies have used aged models despite clear evidence of differences between the response to estrogen deficiency in adult and aged animals. Thus more work is needed focusing on the effects of aging vs. estrogen loss on the cardiovascular system. Published by Elsevier Ireland Ltd.

Molecular Thermodynamics for Cell Biology as Taught with Boxes

PubMed Central

Mayorga, Luis S.; López, María José; Becker, Wayne M.

2012-01-01

Thermodynamic principles are basic to an understanding of the complex fluxes of energy and information required to keep cells alive. These microscopic machines are nonequilibrium systems at the micron scale that are maintained in pseudo-steady-state conditions by very sophisticated processes. Therefore, several nonstandard concepts need to be taught to rationalize why these very ordered systems proliferate actively all over our planet in seeming contradiction to the second law of thermodynamics. We propose a model consisting of boxes with different shapes that contain small balls that are in constant motion due to a stream of air blowing from below. This is a simple macroscopic system that can be easily visualized by students and that can be understood as mimicking the behavior of a set of molecules exchanging energy. With such boxes, the basic concepts of entropy, enthalpy, and free energy can be taught while reinforcing a molecular understanding of the concepts and stressing the stochastic nature of the thermodynamic laws. In addition, time-related concepts, such as reaction rates and activation energy, can be readily visualized. Moreover, the boxes provide an intuitive way to introduce the role in cellular organization of “information” and Maxwell's demons operating under nonequilibrium conditions. PMID:22383615

Molecular thermodynamics for cell biology as taught with boxes.

PubMed

Mayorga, Luis S; López, María José; Becker, Wayne M

2012-01-01

Thermodynamic principles are basic to an understanding of the complex fluxes of energy and information required to keep cells alive. These microscopic machines are nonequilibrium systems at the micron scale that are maintained in pseudo-steady-state conditions by very sophisticated processes. Therefore, several nonstandard concepts need to be taught to rationalize why these very ordered systems proliferate actively all over our planet in seeming contradiction to the second law of thermodynamics. We propose a model consisting of boxes with different shapes that contain small balls that are in constant motion due to a stream of air blowing from below. This is a simple macroscopic system that can be easily visualized by students and that can be understood as mimicking the behavior of a set of molecules exchanging energy. With such boxes, the basic concepts of entropy, enthalpy, and free energy can be taught while reinforcing a molecular understanding of the concepts and stressing the stochastic nature of the thermodynamic laws. In addition, time-related concepts, such as reaction rates and activation energy, can be readily visualized. Moreover, the boxes provide an intuitive way to introduce the role in cellular organization of "information" and Maxwell's demons operating under nonequilibrium conditions.

Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions.

PubMed

Marshall, Clement D; Hu, Michael S; Leavitt, Tripp; Barnes, Leandra A; Lorenz, H Peter; Longaker, Michael T

2018-02-01

Significance: Scarring of the skin from burns, surgery, and injury constitutes a major burden on the healthcare system. Patients affected by major scars, particularly children, suffer from long-term functional and psychological problems. Recent Advances: Scarring in humans is the end result of the wound healing process, which has evolved to rapidly repair injuries. Wound healing and scar formation are well described on the cellular and molecular levels, but truly effective molecular or cell-based antiscarring treatments still do not exist. Recent discoveries have clarified the role of skin stem cells and fibroblasts in the regeneration of injuries and formation of scar. Critical Issues: It will be important to show that new advances in the stem cell and fibroblast biology of scarring can be translated into therapies that prevent and reduce scarring in humans without major side effects. Future Directions: Novel therapies involving the use of purified human cells as well as agents that target specific cells and modulate the immune response to injury are currently undergoing testing. In the basic science realm, researchers continue to refine our understanding of the role that particular cell types play in the development of scar.

Cellular Responses to Mechanical Stress Selected Contribution: A Three-Dimensional Model for Assessment of in Vitro Toxicity in Balaena Mysticetus Renal Tissue

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Coate-Li, L.; Linnehan, R. M.; Hammond, T. G.

2000-01-01

This study established two- and three-dimensional renal proximal tubular cell cultures of the endangered species bowhead whale (Balaena mysticetus), developed SV40-transfected cultures, and cloned the 61-amino acid open reading frame for the metallothionein protein, the primary binding site for heavy metal contamination in mammals. Microgravity research, modulations in mechanical culture conditions (modeled microgravity), and shear stress have spawned innovative approaches to understanding the dynamics of cellular interactions, gene expression, and differentiation in several cellular systems. These investigations have led to the creation of ex vivo tissue models capable of serving as physiological research analogs for three-dimensional cellular interactions. These models are enabling studies in immune function, tissue modeling for basic research, and neoplasia. Three-dimensional cellular models emulate aspects of in vivo cellular architecture and physiology and may facilitate environmental toxicological studies aimed at elucidating biological functions and responses at the cellular level. Marine mammals occupy a significant ecological niche (72% of the Earth's surface is water) in terms of the potential for information on bioaccumulation and transport of terrestrial and marine environmental toxins in high-order vertebrates. Few ex vivo models of marine mammal physiology exist in vitro to accomplish the aforementioned studies. Techniques developed in this investigation, based on previous tissue modeling successes, may serve to facilitate similar research in other marine mammals.

Close Encounters - Probing Proximal Proteins in Live or Fixed Cells.

PubMed

Lönn, Peter; Landegren, Ulf

2017-07-01

The well-oiled machinery of the cellular proteome operates via variable expression, modifications, and interactions of proteins, relaying genomic and transcriptomic information to coordinate cellular functions. In recent years, a number of techniques have emerged that serve to identify sets of proteins acting in close proximity in the course of orchestrating cellular activities. These proximity-dependent assays, including BiFC, BioID, APEX, FRET, and isPLA, have opened up new avenues to examine protein interactions in live or fixed cells. We review herein the current status of proximity-dependent in situ techniques. We compare the advantages and limitations of the methods, underlining recent progress and the growing importance of these techniques in basic research, and we discuss their potential as tools for drug development and diagnostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design of Improved Arithmetic Logic Unit in Quantum-Dot Cellular Automata

NASA Astrophysics Data System (ADS)

Heikalabad, Saeed Rasouli; Gadim, Mahya Rahimpour

2018-06-01

The quantum-dot cellular automata (QCA) can be replaced to overcome the limitation of CMOS technology. An arithmetic logic unit (ALU) is a basic structure of any computer devices. In this paper, design of improved single-bit arithmetic logic unit in quantum dot cellular automata is presented. The proposed structure for ALU has AND, OR, XOR and ADD operations. A unique 2:1 multiplexer, an ultra-efficient two-input XOR and a low complexity full adder are used in the proposed structure. Also, an extended design of this structure is provided for two-bit ALU in this paper. The proposed structure of ALU is simulated by QCADesigner and simulation result is evaluated. Evaluation results show that the proposed design has best performance in terms of area, complexity and delay compared to the previous designs.

Design of Improved Arithmetic Logic Unit in Quantum-Dot Cellular Automata

NASA Astrophysics Data System (ADS)

Heikalabad, Saeed Rasouli; Gadim, Mahya Rahimpour

2018-03-01

The quantum-dot cellular automata (QCA) can be replaced to overcome the limitation of CMOS technology. An arithmetic logic unit (ALU) is a basic structure of any computer devices. In this paper, design of improved single-bit arithmetic logic unit in quantum dot cellular automata is presented. The proposed structure for ALU has AND, OR, XOR and ADD operations. A unique 2:1 multiplexer, an ultra-efficient two-input XOR and a low complexity full adder are used in the proposed structure. Also, an extended design of this structure is provided for two-bit ALU in this paper. The proposed structure of ALU is simulated by QCADesigner and simulation result is evaluated. Evaluation results show that the proposed design has best performance in terms of area, complexity and delay compared to the previous designs.

The physical characteristics of human proteins in different biological functions.

PubMed

Wang, Tengjiao; Tang, Hailin

2017-01-01

The physical properties of gene products are the foundation of their biological functions. In this study, we systematically explored relationships between physical properties and biological functions. The physical properties including origin time, evolution pressure, mRNA and protein stability, molecular weight, hydrophobicity, acidity/alkaline, amino acid compositions, and chromosome location. The biological functions are defined from 4 aspects: biological process, molecular function, cellular component and cell/tissue/organ expression. We found that the proteins associated with basic material and energy metabolism process originated earlier, while the proteins associated with immune, neurological system process etc. originated later. Tissues may have a strong influence on evolution pressure. The proteins associated with energy metabolism are double-stable. Immune and peripheral cell proteins tend to be mRNA stable/protein unstable. There are very few function items with double-unstable of mRNA and protein. The proteins involved in the cell adhesion tend to consist of large proteins with high proportion of small amino acids. The proteins of organic acid transport, neurological system process and amine transport have significantly high hydrophobicity. Interestingly, the proteins involved in olfactory receptor activity tend to have high frequency of aromatic, sulfuric and hydroxyl amino acids.

The physical characteristics of human proteins in different biological functions

PubMed Central

Tang, Hailin

2017-01-01

The physical properties of gene products are the foundation of their biological functions. In this study, we systematically explored relationships between physical properties and biological functions. The physical properties including origin time, evolution pressure, mRNA and protein stability, molecular weight, hydrophobicity, acidity/alkaline, amino acid compositions, and chromosome location. The biological functions are defined from 4 aspects: biological process, molecular function, cellular component and cell/tissue/organ expression. We found that the proteins associated with basic material and energy metabolism process originated earlier, while the proteins associated with immune, neurological system process etc. originated later. Tissues may have a strong influence on evolution pressure. The proteins associated with energy metabolism are double-stable. Immune and peripheral cell proteins tend to be mRNA stable/protein unstable. There are very few function items with double-unstable of mRNA and protein. The proteins involved in the cell adhesion tend to consist of large proteins with high proportion of small amino acids. The proteins of organic acid transport, neurological system process and amine transport have significantly high hydrophobicity. Interestingly, the proteins involved in olfactory receptor activity tend to have high frequency of aromatic, sulfuric and hydroxyl amino acids. PMID:28459865

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

PubMed Central

Oppenheimer, Jack H.; Schwartz, Harold L.; Shapiro, Harvey C.; Bernstein, Gerald; Surks, Martin I.

1970-01-01

Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-125I and T3-131I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine. PMID:5441537

Concise Review: Process Development Considerations for Cell Therapy

PubMed Central

Brieva, Thomas; Raviv, Lior; Rowley, Jon; Niss, Knut; Brandwein, Harvey; Oh, Steve; Karnieli, Ohad

2015-01-01

The development of robust and well-characterized methods of production of cell therapies has become increasingly important as therapies advance through clinical trials toward approval. A successful cell therapy will be a consistent, safe, and effective cell product, regardless of the cell type or application. Process development strategies can be developed to gain efficiency while maintaining or improving safety and quality profiles. This review presents an introduction to the process development challenges of cell therapies and describes some of the tools available to address production issues. This article will provide a summary of what should be considered to efficiently advance a cellular therapy from the research stage through clinical trials and finally toward commercialization. The identification of the basic questions that affect process development is summarized in the target product profile, and considerations for process optimization are discussed. The goal is to identify potential manufacturing concerns early in the process so they may be addressed effectively and thus increase the probability that a therapy will be successful. Significance The present study contributes to the field of cell therapy by providing a resource for those transitioning a potential therapy from the research stage to clinical and commercial applications. It provides the necessary steps that, when followed, can result in successful therapies from both a clinical and commercial perspective. PMID:26315572

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

PubMed

Lu, Zhongyan; Shen, Hong; Shen, Zanming

2018-01-01

In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular immunity, repair, and homeostasis in the rumen epithelium, thereby leading to the switch of concentrate effects from positive to negative with regard to animal production and health. © 2018 The Author(s). Published by S. Karger AG, Basel.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits.

PubMed

Jia, Keran; An, Liyun; Wang, Fukun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing

2016-04-01

To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C(14)-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C(14)-urea breath-test values were significantly higher compared with before training - thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4(+) and CD8(+) T-cell percentages and the CD4(+)/CD8(+) ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. © The Author(s) 2016.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits

PubMed Central

Jia, Keran; An, Liyun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing

2016-01-01

Objective To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. Methods In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C14-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. Results For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C14-urea breath-test values were significantly higher compared with before training – thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4+ and CD8+ T-cell percentages and the CD4+/CD8+ ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Conclusion Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. PMID:26800706

Hegemonic structure of basic, clinical and patented knowledge on Ebola research: a US army reductionist initiative.

PubMed

Fajardo-Ortiz, David; Ortega-Sánchez-de-Tagle, José; Castaño, Victor M

2015-04-19

Ebola hemorrhagic fever (Ebola) is still a highly lethal infectious disease long affecting mainly neglected populations in sub-Saharan Africa. Moreover, this disease is now considered a potential worldwide threat. In this paper, we present an approach to understand how the basic, clinical and patent knowledge on Ebola is organized and intercommunicated and what leading factor could be shaping the evolution of the knowledge translation process for this disease. A combination of citation network analysis; analysis of Medical heading Subject (MeSH) and Gene Ontology (GO) terms, and quantitative content analysis for patents and scientific literature, aimed to map the organization of Ebola research was carried out. We found six putative research fronts (i.e. clusters of high interconnected papers). Three research fronts are basic research on Ebola virus structural proteins: glycoprotein, VP40 and VP35, respectively. There is a fourth research front of basic research papers on pathogenesis, which is the organizing hub of Ebola research. A fifth research front is pre-clinical research focused on vaccines and glycoproteins. Finally, a clinical-epidemiology research front related to the disease outbreaks was identified. The network structure of patent families shows that the dominant design is the use of Ebola virus proteins as targets of vaccines and other immunological treatments. Therefore, patents network organization resembles the organization of the scientific literature. Specifically, the knowledge on Ebola would flow from higher (clinical-epidemiology) to intermediated (cellular-tissular pathogenesis) to lower (molecular interactions) levels of organization. Our results suggest a strong reductionist approach for Ebola research probably influenced by the lethality of the disease. On the other hand, the ownership profile of the patent families network and the main researches relationship with the United State Army suggest a strong involvement of this military institution in Ebola research.

From Syncitium to Regulated Pump: A Cardiac Muscle Cellular Update

ERIC Educational Resources Information Center

Korzick, Donna H.

2011-01-01

The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information…

Traffic Driven Analysis of Cellular and WiFi Networks

ERIC Educational Resources Information Center

Paul, Utpal Kumar

2012-01-01

Since the days Internet traffic proliferated, measurement, monitoring and analysis of network traffic have been critical to not only the basic understanding of large networks, but also to seek improvements in resource management, traffic engineering and security. At the current times traffic in wireless local and wide area networks are facing…

On the safety assessment of human exposure in the proximity of cellular communications base-station antennas at 900, 1800 and 2170 MHz.

PubMed

Martínez-Búrdalo, M; Martín, A; Anguiano, M; Villar, R

2005-09-07

In this work, the procedures for safety assessment in the close proximity of cellular communications base-station antennas at three different frequencies (900, 1800 and 2170 MHz) are analysed. For each operating frequency, we have obtained and compared the distances to the antenna from the exposure places where electromagnetic fields are below reference levels and the distances where the specific absorption rate (SAR) values in an exposed person are below the basic restrictions, according to the European safety guidelines. A high-resolution human body model has been located, in front of each base-station antenna as a worst case, at different distances, to compute whole body averaged SAR and maximum 10 g averaged SAR inside the exposed body. The finite-difference time-domain method has been used for both electromagnetic fields and SAR calculations. This paper shows that, for antenna-body distances in the near zone of the antenna, the fact that averaged field values be below the reference levels could, at certain frequencies, not guarantee guidelines compliance based on basic restrictions.

The effect of tributyltin on human eosinophilic [correction of eosinophylic] leukemia EoL-1 cells.

PubMed

Sroka, Jolanta; Włosiak, Przemysław; Wilk, Anna; Antonik, Justyna; Czyz, Jarosław; Madeja, Zbigniew

2008-01-01

Organotin compounds are chemicals that are widely used in industry and agriculture as plastic stabilizers, catalysts and biocides. Many of them, including tributyltin (TBT), have been detected in human food and, as a consequence, detectable levels have been found in human blood. As organotin compounds were shown to possess immunotoxic activity, we focused our attention on the effect of TBT on the basic determinants of the function of eosinophils, i.e. cell adhesiveness and motility. We used human eosinophylic leukemia EoL-1 cells, a common in vitro cellular model of human eosinophils. Here, we demonstrate that TBT causes a dose-dependent decrease in the viability of EoL-1 cells. When administered at sub-lethal concentrations, TBT significantly decreases the adhesion of EoL-1 cells to human fibroblasts (HSFs) and inhibits their migration on fibroblast surfaces. Since the basic function of eosinophils is to invade inflamed tissues, our results indicate that TBT, and possibly other organotin compounds, may affect major cellular properties involved in the determination of in vivo eosinophil function.

Mechano-biological Coupling of Cellular Responses to Microgravity

NASA Astrophysics Data System (ADS)

Long, Mian; Wang, Yuren; Zheng, Huiqiong; Shang, Peng; Duan, Enkui; Lü, Dongyuan

2015-11-01

Cellular response to microgravity is a basic issue in space biological sciences as well as space physiology and medicine. It is crucial to elucidate the mechano-biological coupling mechanisms of various biological organisms, since, from the principle of adaptability, all species evolved on the earth must possess the structure and function that adapts their living environment. As a basic element of an organism, a cell usually undergoes mechanical and chemical remodeling to sense, transmit, transduce, and respond to the alteration of gravitational signals. In the past decades, new computational platforms and experimental methods/techniques/devices are developed to mimic the biological effects of microgravity environment from the viewpoint of biomechanical approaches. Mechanobiology of plant gravisensing in the responses of statolith movements along the gravity vector and the relevant signal transduction and molecular regulatory mechanisms are investigated at gene, transcription, and protein levels. Mechanotransduction of bone or immune cell responses and stem cell development and tissue histogenesis are elucidated under microgravity. In this review, several important issues are briefly discussed. Future issues on gravisensing and mechanotransducing mechanisms are also proposed for ground-based studies as well as space missions.

Molecular and Cellular Biophysics

NASA Astrophysics Data System (ADS)

Jackson, Meyer B.

2006-01-01

Molecular and Cellular Biophysics provides advanced undergraduate and graduate students with a foundation in the basic concepts of biophysics. Students who have taken physical chemistry and calculus courses will find this book an accessible and valuable aid in learning how these concepts can be used in biological research. The text provides a rigorous treatment of the fundamental theories in biophysics and illustrates their application with examples. Conformational transitions of proteins are studied first using thermodynamics, and subsequently with kinetics. Allosteric theory is developed as the synthesis of conformational transitions and association reactions. Basic ideas of thermodynamics and kinetics are applied to topics such as protein folding, enzyme catalysis and ion channel permeation. These concepts are then used as the building blocks in a treatment of membrane excitability. Through these examples, students will gain an understanding of the general importance and broad applicability of biophysical principles to biological problems. Offers a unique synthesis of concepts across a wide range of biophysical topics Provides a rigorous theoretical treatment, alongside applications in biological systems Author has been teaching biophysics for nearly 25 years

Human physiology in space

NASA Technical Reports Server (NTRS)

Vernikos, J.

1996-01-01

The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

Autoinflammatory Skin Disorders: The Inflammasomme in Focus

PubMed Central

Gurung, Prajwal; Kanneganti, Thirumala-Devi

2016-01-01

Autoinflammatory skin disorders are a group of heterogeneous diseases that include diseases such as cryopyrin-associated periodic syndrome (CAPS) and familial Mediterranean fever (FMF). Therapeutic strategies targeting IL-1 cytokines have proved helpful in ameliorating some of these diseases. While inflammasomes are the major regulators of IL-1 cytokines, inflammasome-independent complexes can also process IL-1 cytokines. Herein, we focus on recent advances in our understanding of how IL-1 cytokines, stemming from inflammasome-dependent and -independent pathways are involved in the regulation of skin conditions. Importantly, we discuss several mouse models of skin inflammation generated to help elucidate the basic cellular and molecular effects and modulation of IL-1 in the skin. Such models offer perspectives on how these signaling pathways could be targeted to improve therapeutic approaches in the treatment of these rare and debilitating inflammatory skin disorders. PMID:27267764

Extinction threshold for spatial forest dynamics with height structure.

PubMed

Garcia-Domingo, Josep L; Saldaña, Joan

2011-05-07

We present a pair-approximation model for spatial forest dynamics defined on a regular lattice. The model assumes three possible states for a lattice site: empty (gap site), occupied by an immature tree, and occupied by a mature tree, and considers three nonlinearities in the dynamics associated to the processes of light interference, gap expansion, and recruitment. We obtain an expression of the basic reproduction number R(0) which, in contrast to the one obtained under the mean-field approach, uses information about the spatial arrangement of individuals close to extinction. Moreover, we analyze the corresponding survival-extinction transition of the forest and the spatial correlations among gaps, immature and mature trees close to this critical point. Predictions of the pair-approximation model are compared with those of a cellular automaton. Copyright © 2011 Elsevier Ltd. All rights reserved.

Real time non invasive imaging of fatty acid uptake in vivo

PubMed Central

Henkin, Amy H.; Cohen, Allison S.; Dubikovskaya, Elena A.; Park, Hyo Min; Nikitin, Gennady F.; Auzias, Mathieu G.; Kazantzis, Melissa; Bertozzi, Carolyn R.; Stahl, Andreas

2012-01-01

Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin-sensitivity. To enable non-invasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real-time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models. PMID:22928772

Neuromechanics of crawling in D. melanogaster larvae

NASA Astrophysics Data System (ADS)

Pehlevan, Cengiz; Paoletti, Paolo; Mahadevan, L.

2015-03-01

Nervous system, body and environment interact in non-trivial ways to generate locomotion and thence behavior in an organism. Here we present a minimal integrative mathematical model to describe the simple behavior of forward crawling in Drosophila larvae. Our model couples the excitation-inhibition circuits in the nervous system to force production in the muscles and body movement in a frictional environment, which in turn leads to a proprioceptive signal that feeds back to the nervous system. Our results explain the basic observed phenomenology of crawling with or without proprioception, and elucidate the stabilizing role of proprioception in crawling with respect to external and internal perturbations. Our integrated approach allows us to make testable predictions on the effect of changing body-environment interactions on crawling, and serves as a substrate for the development of hierarchical models linking cellular processes to behavior.

From Genes to Networks: Characterizing Gene-Regulatory Interactions in Plants.

PubMed

Kaufmann, Kerstin; Chen, Dijun

2017-01-01

Plants, like other eukaryotes, have evolved complex mechanisms to coordinate gene expression during development, environmental response, and cellular homeostasis. Transcription factors (TFs), accompanied by basic cofactors and posttranscriptional regulators, are key players in gene-regulatory networks (GRNs). The coordinated control of gene activity is achieved by the interplay of these factors and by physical interactions between TFs and DNA. Here, we will briefly outline recent technological progress made to elucidate GRNs in plants. We will focus on techniques that allow us to characterize physical interactions in GRNs in plants and to analyze their regulatory consequences. Targeted manipulation allows us to test the relevance of specific gene-regulatory interactions. The combination of genome-wide experimental approaches with mathematical modeling allows us to get deeper insights into key-regulatory interactions and combinatorial control of important processes in plants.

Workshop summary. Biomedical and Space-Related Research with Heavy Ions at the BEVALAC

NASA Technical Reports Server (NTRS)

Schimmerling, W.; Curtis, S. B.

1989-01-01

The authors provide an overview of papers presented at a workshop on Biomedical and Space-Related Research with Heavy Ions at the BEVALAC at Lawrence Berkeley Laboratory. Goals of the meeting were to determine the critical experiments using heavy ions as probes in radiation physics, radiation chemistry, macromolecular and cellular biology, evolution science, basic neurophysiology, and medical therapies; how beam lines and facilities at Lawrence Berkeley Laboratory can be improved for these experiments; and implications in priorities and funding for national policy. Workshop topics included physics and facilities, cellular and molecular biology, tissue radiobiology, and the future of heavy ion research.

Effect of salt solutions on radiosensitivity of mammalian cells. I. Specific ion effects.

PubMed

Raaphorst, G P; Kruuv, J

1977-07-01

The radiation isodose survival curve of cells subjected to a wide concentration range of sucrose solutions has two maxima separated by a minimum. Both cations and anions can alter the cellular radiosensitivity above and beyond the osmotic effect observed for cells treated with sucrose solutions. The basic shape of the isodose curve can also be modulated by changes in temperature and solution exposure times. Some of these alterations in radiosensitivity may be related to changes in the amount and structure of cellular water or macromolecular conformation or to the direct effect of the ions, expecially at high solute concentrations.

National Heart, Lung, and Blood Institute and the translation of cardiovascular discoveries into therapeutic approaches.

PubMed

Galis, Zorina S; Black, Jodi B; Skarlatos, Sonia I

2013-04-26

The molecular causes of ≈4000 medical conditions have been described, yet only 5% have associated therapies. For decades, the average time for drug development through approval has taken 10 to 20 years. In recent years, the serious challenges that confront the private sector have made it difficult to capitalize on new opportunities presented by advances in genomics and cellular therapies. Current trends are disturbing. Pharmaceutical companies are reducing their investments in research, and biotechnology companies are struggling to obtain venture funds. To support early-stage translation of the discoveries in basic science, the National Institutes of Health and the National Heart, Lung, and Blood Institute have developed new approaches to facilitating the translation of basic discoveries into clinical applications and will continue to develop a variety of programs that create teams of academic investigators and industry partners. The goal of these programs is to maximize the public benefit of investment of taxpayer dollars in biomedical research and to lessen the risk required for industry partners to make substantial investments. This article highlights several examples of National Heart, Lung, and Blood Institute-initiated translational programs and National Institutes of Health translational resources designed to catalyze and enable the earliest stages of the biomedical product development process. The translation of latest discoveries into therapeutic approaches depends on continued federal funding to enhance the early stages of the product development process and to stimulate and catalyze partnerships between academia, industry, and other sources of capital.

Analysis of Human Mobility Based on Cellular Data

NASA Astrophysics Data System (ADS)

Arifiansyah, F.; Saptawati, G. A. P.

2017-01-01

Nowadays not only adult but even teenager and children have then own mobile phones. This phenomena indicates that the mobile phone becomes an important part of everyday’s life. Based on these indication, the amount of cellular data also increased rapidly. Cellular data defined as the data that records communication among mobile phone users. Cellular data is easy to obtain because the telecommunications company had made a record of the data for the billing system of the company. Billing data keeps a log of the users cellular data usage each time. We can obtained information from the data about communication between users. Through data visualization process, an interesting pattern can be seen in the raw cellular data, so that users can obtain prior knowledge to perform data analysis. Cellular data processing can be done using data mining to find out human mobility patterns and on the existing data. In this paper, we use frequent pattern mining and finding association rules to observe the relation between attributes in cellular data and then visualize them. We used weka tools for finding the rules in stage of data mining. Generally, the utilization of cellular data can provide supporting information for the decision making process and become a data support to provide solutions and information needed by the decision makers.

Mechanical properties of porous and cellular materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sieradzki, K.; Green, D.J.; Gibson, L.J.

1991-01-01

This symposium successfully brought scientists together from a wide variety of disciplines to focus on the mechanical behavior of porous and cellular solids composed of metals, ceramics, polymers, or biological materials. For cellular materials, papers ranged from processing techniques through microstructure-mechanical property relationships to design. In an overview talk, Mike Ashby (Cambridge Univ.) showed how porous cellular materials can be more efficient than dense materials in designs that require minimum weight. He indicated that many biological materials have been able to accomplish such efficiency but there exists an opportunity to design even more efficient, manmade materials controlling microstructures at differentmore » scale levels. In the area of processing, James Aubert (Sandia National Laboratories) discussed techiques for manipulating polymersolvent phase equilibria to control the microstructure of microcellular foams. Other papers on processing discussed the production of cellular ceramics by CVD, HIPing and sol- gel techniques. Papers on the mechanical behavior of cellular materials considered various ceramics microcellular polymers, conventional polymer foams and apples. There were also contributions that considered optimum design procedures for cellular materials. Steven Cowin (City Univ. of New York) discussed procedures to match the discrete microstructural aspects of cellular materials with the continuum mechanics approach to their elastic behavior.« less

Homeostasis 5: nurses as external agents of control in breast cancer.

PubMed

Clancy, John; McVicar, Andrew

Breast cancer is caused by a homeostatic imbalance of cell division. Healthcare practitioners need to understand cellular activities to appreciate the physiological basis of health (homeostasis), the pathophysiological basis of illness and the physiological rationale of healthcare. Cells are the 'basic unit of life' (Clancy and McVicar, 2011a). This article describes normal cell division and the anatomy and physiology of the breast and, using a case study, will show how breast cancer is a homeostatic imbalance of cell division. There are analogies between the components of homeostasis and the components of the nursing (healthcare) process (Clancy and McVicar, 2011b) in the condition of breast cancer. After reading this article, nurses should be able to: understand that breast cancer is a cellular hence chemical imbalance that causes uncontrollable mitotic division of breast cells; understand how the cell cycle of cancer cells differs from that of normal cells; identify nature-nurture interactions involved in the aetiology of breast cancer; understand that when caring for people with breast cancer, health professionals including oncology nurses are acting as external agents of homeostatic control as the patient 'recovers' from breast cancer, and also to some extent when reducing signs and symptoms, hence quality of life, by providing palliative care.

Helicase-inactivating mutations as a basis for dominant negative phenotypes

PubMed Central

Wu, Yuliang

2010-01-01

There is ample evidence from studies of both unicellular and multicellular organisms that helicase-inactivating mutations lead to cellular dysfunction and disease phenotypes. In this review, we will discuss the mechanisms underlying the basis for abnormal phenotypes linked to mutations in genes encoding DNA helicases. Recent evidence demonstrates that a clinically relevant patient missense mutation in Fanconi Anemia Complementation Group J exerts detrimental effects on the biochemical activities of the FANC J helicase, and these molecular defects are responsible for aberrant genomic stability and a poor DNA damage response. The ability of FANC J to use the energy from AT P hydrolysis to produce the force required to unwind duplex or G-quadruplex DNA structures or destabilize protein bound to DNA is required for its DNA repair functions in vivo. Strikingly, helicase-inactivating mutations can exert a spectrum of dominant negative phenotypes, indicating that expression of the mutant helicase protein potentially interferes with normal DNA metabolism and has an effect on basic cellular processes such as DNA replication, the DNA damage response and protein trafficking. This review emphasizes that future studies of clinically relevant mutations in helicase genes will be important to understand the molecular pathologies of the associated diseases and their impact on heterozygote carriers. PMID:20980836

Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease.

PubMed

Wancket, Lyn M; Frazier, W Joshua; Liu, Yusen

2012-02-13

Mitogen-activated protein kinases (MAPKs) are key regulators of cellular physiology and immune responses, and abnormalities in MAPKs are implicated in many diseases. MAPKs are activated by MAPK kinases through phosphorylation of the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr domain, where Xaa represents amino acid residues characteristic of distinct MAPK subfamilies. Since MAPKs play a crucial role in a variety of cellular processes, a delicate regulatory network has evolved to control their activities. Over the past two decades, a group of dual specificity MAPK phosphatases (MKPs) has been identified that deactivates MAPKs. Since MAPKs can enhance MKP activities, MKPs are considered as an important feedback control mechanism that limits the MAPK cascades. This review outlines the role of MKP-1, a prototypical MKP family member, in physiology and disease. We will first discuss the basic biochemistry and regulation of MKP-1. Next, we will present the current consensus on the immunological and physiological functions of MKP-1 in infectious, inflammatory, metabolic, and nervous system diseases as revealed by studies using animal models. We will also discuss the emerging evidence implicating MKP-1 in human disorders. Finally, we will conclude with a discussion of the potential for pharmacomodulation of MKP-1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Toward Multiscale Models of Cyanobacterial Growth: A Modular Approach

PubMed Central

Westermark, Stefanie; Steuer, Ralf

2016-01-01

Oxygenic photosynthesis dominates global primary productivity ever since its evolution more than three billion years ago. While many aspects of phototrophic growth are well understood, it remains a considerable challenge to elucidate the manifold dependencies and interconnections between the diverse cellular processes that together facilitate the synthesis of new cells. Phototrophic growth involves the coordinated action of several layers of cellular functioning, ranging from the photosynthetic light reactions and the electron transport chain, to carbon-concentrating mechanisms and the assimilation of inorganic carbon. It requires the synthesis of new building blocks by cellular metabolism, protection against excessive light, as well as diurnal regulation by a circadian clock and the orchestration of gene expression and cell division. Computational modeling allows us to quantitatively describe these cellular functions and processes relevant for phototrophic growth. As yet, however, computational models are mostly confined to the inner workings of individual cellular processes, rather than describing the manifold interactions between them in the context of a living cell. Using cyanobacteria as model organisms, this contribution seeks to summarize existing computational models that are relevant to describe phototrophic growth and seeks to outline their interactions and dependencies. Our ultimate aim is to understand cellular functioning and growth as the outcome of a coordinated operation of diverse yet interconnected cellular processes. PMID:28083530

Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at the trans-Golgi Network To Promote Virus Replication

PubMed Central

Taylor, Kathryne E.

2015-01-01

ABSTRACT It has recently been proposed that the herpes simplex virus (HSV) protein ICP0 has cytoplasmic roles in blocking antiviral signaling and in promoting viral replication in addition to its well-known proteasome-dependent functions in the nucleus. However, the mechanisms through which it produces these effects remain unclear. While investigating this further, we identified a novel cytoplasmic interaction between ICP0 and the poorly characterized cellular protein WDR11. During an HSV infection, WDR11 undergoes a dramatic change in localization at late times in the viral replication cycle, moving from defined perinuclear structures to a dispersed cytoplasmic distribution. While this relocation was not observed during infection with viruses other than HSV-1 and correlated with efficient HSV-1 replication, the redistribution was found to occur independently of ICP0 expression, instead requiring viral late gene expression. We demonstrate for the first time that WDR11 is localized to the trans-Golgi network (TGN), where it interacts specifically with some, but not all, HSV virion components, in addition to ICP0. Knockdown of WDR11 in cultured human cells resulted in a modest but consistent decrease in yields of both wild-type and ICP0-null viruses, in the supernatant and cell-associated fractions, without affecting viral gene expression. Although further study is required, we propose that WDR11 participates in viral assembly and/or secondary envelopment. IMPORTANCE While the TGN has been proposed to be the major site of HSV-1 secondary envelopment, this process is incompletely understood, and in particular, the role of cellular TGN components in this pathway is unknown. Additionally, little is known about the cellular functions of WDR11, although the disruption of this protein has been implicated in multiple human diseases. Therefore, our finding that WDR11 is a TGN-resident protein that interacts with specific viral proteins to enhance viral yields improves both our understanding of basic cellular biology as well as how this protein is co-opted by HSV. PMID:26178983

25 CFR 15.11 - What are the basic steps of the probate process?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false What are the basic steps of the probate process? 15.11 Section 15.11 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR PROBATE PROBATE OF INDIAN... are the basic steps of the probate process? The basic steps of the probate process are: (a) We learn...

How to Make a Synthetic Multicellular Computer

PubMed Central

Macia, Javier; Sole, Ricard

2014-01-01

Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined. PMID:24586222

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

PubMed

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Mammalian synthetic biology for studying the cell

PubMed Central

Mathur, Melina; Xiang, Joy S.

2017-01-01

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. PMID:27932576

Adoptive cellular therapy for chronic lymphocytic leukemia and B cell malignancies. CARs and more.

PubMed

Castro, Januario E; Kipps, Thomas J

2016-03-01

Treatment of patients with chronic lymphocytic leukemia and other B cell malignancies is evolving very rapidly. We have observed the quick transition during the last couple of years, from chemo-immunotherapy based treatments to oral targeted therapies based on B cell receptor signaling and Bcl-2 inhibitors, as well as the increasing use of second generation glyco-engineered antibodies. The next wave of revolution in the treatment for this conditions is approaching and it will be based on strategies that harness the power of the immune system to fight cancer. In the center of this biotechnological revolution is cellular engineering, the field that had made possible to redirect the immune system effector cells to achieve a more effective and targeted adoptive cellular therapy. In this chapter, we will review the historical context of these scientific developments, the most recent basic and clinical research in the field and some opinions regarding the future of adoptive cellular therapy in CLL and other B cell malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biophysics at the Boundaries: The Next Problem Sets

NASA Astrophysics Data System (ADS)

Skolnick, Malcolm

2009-03-01

The interface between physics and biology is one of the fastest growing subfields of physics. As knowledge of such topics as cellular processes and complex ecological systems advances, researchers have found that progress in understanding these and other systems requires application of more quantitative approaches. Today, there is a growing demand for quantitative and computational skills in biological research and the commercialization of that research. The fragmented teaching of science in our universities still leaves biology outside the quantitative and mathematical culture that is the foundation of physics. This is particularly inopportune at a time when the needs for quantitative thinking about biological systems are exploding. More physicists should be encouraged to become active in research and development in the growing application fields of biophysics including molecular genetics, biomedical imaging, tissue generation and regeneration, drug development, prosthetics, neural and brain function, kinetics of nonequilibrium open biological systems, metabolic networks, biological transport processes, large-scale biochemical networks and stochastic processes in biochemical systems to name a few. In addition to moving into basic research in these areas, there is increasing opportunity for physicists in industry beginning with entrepreneurial roles in taking research results out of the laboratory and in the industries who perfect and market the inventions and developments that physicists produce. In this talk we will identify and discuss emerging opportunities for physicists in biophysical and biotechnological pursuits ranging from basic research through development of applications and commercialization of results. This will include discussion of the roles of physicists in non-traditional areas apart from academia such as patent law, financial analysis and regulatory science and the problem sets assigned in education and training that will enable future biophysicists to fill these roles.

Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex.

PubMed

Lübke, Joachim; Feldmeyer, Dirk

2007-07-01

A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal 'microcircuits'. In the last decade the 'barrel' field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.

The BioScope Initiative: Integrating Technology into the Biology Classroom.

ERIC Educational Resources Information Center

Ashburn, Sarah J.; Eichinger, David C.; Witham, Shelly A.; Cross, Vanessa D.; Krockover, Gerald H.; Pae, Tae-Il; Islam, Samantha; Robinson, J. Paul

2002-01-01

Reports on the quantitative and qualitative assessment of the CD-ROM "Cell Structure and Function" which includes five sections: (1) Basics; (2) Simple Cell; (3) Cell Viewer; (4) Cellular Changes; and (5) Handles. Evaluates the effectiveness of the CD-ROM with the participation of (n=65) students. Applies both qualitative and statistical methods.…

"Sickle Cell Anemia: Tracking down a Mutation": An Interactive Learning Laboratory That Communicates Basic Principles of Genetics and Cellular Biology

ERIC Educational Resources Information Center

Jarrett, Kevin; Williams, Mary; Horn, Spencer; Radford, David; Wyss, J. Michael

2016-01-01

"Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients…

High-strength cellular ceramic composites with 3D microarchitecture.

PubMed

Bauer, Jens; Hengsbach, Stefan; Tesari, Iwiza; Schwaiger, Ruth; Kraft, Oliver

2014-02-18

To enhance the strength-to-weight ratio of a material, one may try to either improve the strength or lower the density, or both. The lightest solid materials have a density in the range of 1,000 kg/m(3); only cellular materials, such as technical foams, can reach considerably lower values. However, compared with corresponding bulk materials, their specific strength generally is significantly lower. Cellular topologies may be divided into bending- and stretching-dominated ones. Technical foams are structured randomly and behave in a bending-dominated way, which is less weight efficient, with respect to strength, than stretching-dominated behavior, such as in regular braced frameworks. Cancellous bone and other natural cellular solids have an optimized architecture. Their basic material is structured hierarchically and consists of nanometer-size elements, providing a benefit from size effects in the material strength. Designing cellular materials with a specific microarchitecture would allow one to exploit the structural advantages of stretching-dominated constructions as well as size-dependent strengthening effects. In this paper, we demonstrate that such materials may be fabricated. Applying 3D laser lithography, we produced and characterized micro-truss and -shell structures made from alumina-polymer composite. Size-dependent strengthening of alumina shells has been observed, particularly when applied with a characteristic thickness below 100 nm. The presented artificial cellular materials reach compressive strengths up to 280 MPa with densities well below 1,000 kg/m(3).

Selected contribution: a three-dimensional model for assessment of in vitro toxicity in balaena mysticetus renal tissue

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Coate-Li, L.; Linnehan, R. M.; Hammond, T. G.

2000-01-01

This study established two- and three-dimensional renal proximal tubular cell cultures of the endangered species bowhead whale (Balaena mysticetus), developed SV40-transfected cultures, and cloned the 61-amino acid open reading frame for the metallothionein protein, the primary binding site for heavy metal contamination in mammals. Microgravity research, modulations in mechanical culture conditions (modeled microgravity), and shear stress have spawned innovative approaches to understanding the dynamics of cellular interactions, gene expression, and differentiation in several cellular systems. These investigations have led to the creation of ex vivo tissue models capable of serving as physiological research analogs for three-dimensional cellular interactions. These models are enabling studies in immune function, tissue modeling for basic research, and neoplasia. Three-dimensional cellular models emulate aspects of in vivo cellular architecture and physiology and may facilitate environmental toxicological studies aimed at elucidating biological functions and responses at the cellular level. Marine mammals occupy a significant ecological niche (72% of the Earth's surface is water) in terms of the potential for information on bioaccumulation and transport of terrestrial and marine environmental toxins in high-order vertebrates. Few ex vivo models of marine mammal physiology exist in vitro to accomplish the aforementioned studies. Techniques developed in this investigation, based on previous tissue modeling successes, may serve to facilitate similar research in other marine mammals.

Role of the Adenovirus DNA-Binding Protein in In Vitro Adeno-Associated Virus DNA Replication

PubMed Central

Ward, Peter; Dean, Frank B.; O’Donnell, Michael E.; Berns, Kenneth I.

1998-01-01

A basic question in adeno-associated virus (AAV) biology has been whether adenovirus (Ad) infection provided any function which directly promoted replication of AAV DNA. Previously in vitro assays for AAV DNA replication, using linear duplex AAV DNA as the template, uninfected or Ad-infected HeLa cell extracts, and exogenous AAV Rep protein, demonstrated that Ad infection provides a direct helper effect for AAV DNA replication. It was shown that the nature of this helper effect was to increase the processivity of AAV DNA replication. Left unanswered was the question of whether this effect was the result of cellular factors whose activity was enhanced by Ad infection or was the result of direct participation of Ad proteins in AAV DNA replication. In this report, we show that in the in vitro assay, enhancement of processivity occurs with the addition of either the Ad DNA-binding protein (Ad-DBP) or the human single-stranded DNA-binding protein (replication protein A [RPA]). Clearly Ad-DBP is present after Ad infection but not before, whereas the cellular level of RPA is not apparently affected by Ad infection. However, we have not measured possible modifications of RPA which might occur after Ad infection and affect AAV DNA replication. When the substrate for replication was an AAV genome inserted into a plasmid vector, RPA was not an effective substitute for Ad-DBP. Extracts supplemented with Ad-DBP preferentially replicated AAV sequences rather than adjacent vector sequences; in contrast, extracts supplemented with RPA preferentially replicated vector sequences. PMID:9420241

Large-scale topology and the default mode network in the mouse connectome

PubMed Central

Stafford, James M.; Jarrett, Benjamin R.; Miranda-Dominguez, Oscar; Mills, Brian D.; Cain, Nicholas; Mihalas, Stefan; Lahvis, Garet P.; Lattal, K. Matthew; Mitchell, Suzanne H.; David, Stephen V.; Fryer, John D.; Nigg, Joel T.; Fair, Damien A.

2014-01-01

Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans. PMID:25512496

Genomic Signal Processing: Predicting Basic Molecular Biological Principles

NASA Astrophysics Data System (ADS)

Alter, Orly

2005-03-01

Advances in high-throughput technologies enable acquisition of different types of molecular biological data, monitoring the flow of biological information as DNA is transcribed to RNA, and RNA is translated to proteins, on a genomic scale. Future discovery in biology and medicine will come from the mathematical modeling of these data, which hold the key to fundamental understanding of life on the molecular level, as well as answers to questions regarding diagnosis, treatment and drug development. Recently we described data-driven models for genome-scale molecular biological data, which use singular value decomposition (SVD) and the comparative generalized SVD (GSVD). Now we describe an integrative data-driven model, which uses pseudoinverse projection (1). We also demonstrate the predictive power of these matrix algebra models (2). The integrative pseudoinverse projection model formulates any number of genome-scale molecular biological data sets in terms of one chosen set of data samples, or of profiles extracted mathematically from data samples, designated the ``basis'' set. The mathematical variables of this integrative model, the pseudoinverse correlation patterns that are uncovered in the data, represent independent processes and corresponding cellular states (such as observed genome-wide effects of known regulators or transcription factors, the biological components of the cellular machinery that generate the genomic signals, and measured samples in which these regulators or transcription factors are over- or underactive). Reconstruction of the data in the basis simulates experimental observation of only the cellular states manifest in the data that correspond to those of the basis. Classification of the data samples according to their reconstruction in the basis, rather than their overall measured profiles, maps the cellular states of the data onto those of the basis, and gives a global picture of the correlations and possibly also causal coordination of these two sets of states. Mapping genome-scale protein binding data using pseudoinverse projection onto patterns of RNA expression data that had been extracted by SVD and GSVD, a novel correlation between DNA replication initiation and RNA transcription during the cell cycle in yeast, that might be due to a previously unknown mechanism of regulation, is predicted. (1) Alter & Golub, Proc. Natl. Acad. Sci. USA 101, 16577 (2004). (2) Alter, Golub, Brown & Botstein, Miami Nat. Biotechnol. Winter Symp. 2004 (www.med.miami.edu/mnbws/alter-.pdf)

Biodynsensing: Sensing Through Dynamics of Hybrid Affinity/Cellular Platforms; Towards Appraisal of Environmental and Biological Risks of Nanobiotechnology

NASA Astrophysics Data System (ADS)

Gheorghiu, E.; Gheorghiu, M.; David, S.; Polonschii, C.

Chemical cues and nano-topographies present on the surface or in the extracellular medium strongly influence the fate and adhesion of biological cells. Careful tuning of cell—matrix interaction via engineered surfaces, either attractive or repulsive, require non-invasive, long time monitoring capabilities and lay the foundation of sensing platforms for risk assessment. Aiming to assess changes underwent by biointerfaces due to cell—environment interaction (in particular nanotechnology products), we have developed hybrid cellular platforms allowing for time based dual assays, i.e., impedance/dielectric spectroscopy (IS) and Surface Plasmon Resonance (SPR). Such platforms comprising Flow Injection Analysis (FIA) have been advanced to assess the interaction between selected (normal and malignant) cells and nano-patterned and/or chemically modified surfaces, as well as the impact of engineered nanoparticles, revealed by the related changes exhibited by cell membrane, morphology, adhesion and monolayer integrity. Besides experimental aspects dealing with measurement set-up, we will emphasize theoretical aspects related to: dielectric modeling. Aiming for a quantitative approach, microscopic models on dielectric behavior of ensembles of interconnected cells have been developed and their capabilities will be outlined within the presentation. Assessment of affinity reactions as revealed by dielectric/impedance assays of biointerfaces. Modeling the dynamics of the impedance in relation to the “quality” of cell layer and sensor's active surface, this study presents further developments of our approach described in Analytical Chemistry, 2002. Data analysis. This issue is related to the following basic question: Are there “simple” Biosensing Platforms? When coping with cellular platforms, either in suspension or immobilized (on filters, adhered on surfaces or entrapped, e.g., on using set-ups) there is an intrinsic nonlinear behavior of biological systems related to cellular mechanisms involved in sensing, i.e., adaptation to stimuli. This should not mean that when coping with living cells, stray effects might not also corrupt the measurement itself, introducing distinct dynamics. Besides targeted/specific process, analytical platforms might exhibit additional ones due to “stray influences” that could include the effect of, e.g.: supporting matrix, nonspecific binding and temperature variation. Stray processes interfere with the desired ones and the measured data could display a non-monotonous behavior.

Aging of cell membranes: facts and theories.

PubMed

Zs-Nagy, Imre

2014-01-01

This chapter is intended to outline the main results of a research trend realized by the author during the last 45 years, focused on the main role played by the cell membrane in the aging process. It is a very wide field; therefore, the reader cannot expect in this limited space a detailed description, but will be given a wide, interdisciplinary insight into the main facts and theories regarding cellular aging. The central idea described here is the concept called the membrane hypothesis of aging (MHA). The history, the chemical roots, physicochemical facts, biophysical processes, as well as the obligatory biochemical consequences are all touched in by indicating the most important sources of detailed knowledge for those who are more interested in the basic biology of the aging process. This chapter covers also the available anti-aging interventions on the cell membrane by means of the centrophenoxine treatment based on the MHA. It also briefly interprets the possibilities of a just developing anti-aging method by using the recombinant human growth hormone, essential basis of which is the species specificity, and the general presence of receptors of this hormone in the plasma membrane of all types of cells.

Final Report for Regulation of Embryonic Development in Higher Plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, John J.

2013-10-22

The overall goal of the project was to define the cellular processes that underlie embryo development in plants at a mechanistic level. Our studies focused on a critical transcriptional regulator, Arabidopsis LEAFY COTYLEDON (LEC1), that is necessary and sufficient to induce processes required for embryo development. Because LEC1 regulates lipid accumulation during the maturation phase of embryo development, information about LEC1 may be useful in designing approaches to enhance biofuel production in plants. During the tenure of this project, we determined the molecular mechanisms by which LEC1 acts as a transcription factor in embryos. We also identified genes directly regulatedmore » by LEC1 and showed that many of these genes are involved in maturation processes. This information has been useful in dissecting the gene regulatory networks controlling embryo development. Finally, LEC1 is a novel isoform of a transcription factor that is conserved among eukaryotes, and LEC1 is active primarily in seeds. Therefore, we determined that the LEC1-type transcription factors first appeared in lycophytes during land plant evolution. Together, this study provides basic information that has implications for biofuel production.« less

Mammalian synthetic biology for studying the cell.

PubMed

Mathur, Melina; Xiang, Joy S; Smolke, Christina D

2017-01-02

Synthetic biology is advancing the design of genetic devices that enable the study of cellular and molecular biology in mammalian cells. These genetic devices use diverse regulatory mechanisms to both examine cellular processes and achieve precise and dynamic control of cellular phenotype. Synthetic biology tools provide novel functionality to complement the examination of natural cell systems, including engineered molecules with specific activities and model systems that mimic complex regulatory processes. Continued development of quantitative standards and computational tools will expand capacities to probe cellular mechanisms with genetic devices to achieve a more comprehensive understanding of the cell. In this study, we review synthetic biology tools that are being applied to effectively investigate diverse cellular processes, regulatory networks, and multicellular interactions. We also discuss current challenges and future developments in the field that may transform the types of investigation possible in cell biology. © 2017 Mathur et al.

Structure and Function of Viral Deubiquitinating Enzymes.

PubMed

Bailey-Elkin, Ben A; Knaap, Robert C M; Kikkert, Marjolein; Mark, Brian L

2017-11-10

Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication. DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. Here, we provide an overview of the structural biology of these fascinating viral enzymes and their role innate immune evasion and viral replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

The SUMO Pathway in Mitosis.

PubMed

Mukhopadhyay, Debaditya; Dasso, Mary

2017-01-01

Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.

Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways: Potential for Treating Age-related Retinal Degeneration

PubMed Central

Haeri, Mohammad; Knox, Barry E

2012-01-01

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) and their aggregation impair normal cellular function and can be toxic, leading to cell death. Prolonged expression of misfolded proteins triggers ER stress, which initiates a cascade of reactions called the unfolded protein response (UPR). Protein misfolding is the basis for a variety of disorders known as ER storage or conformational diseases. There are an increasing number of eye disorders associated with misfolded proteins and pathologic ER responses, including retinitis pigmentosa (RP). Herein we review the basic cellular and molecular biology of UPR with focus on pathways that could be potential targets for treating retinal degenerative diseases. PMID:22737387

The study and application of four kinds of organic ion-selective microsensors

NASA Astrophysics Data System (ADS)

Yu, Bi; Zheng, Xiao; Feng, Chu; Hong, Wen-Bing; Liu, Jun-Tao; Wang, Ru-Jiang

1991-09-01

Four kinds of organic ion-selective microelectrodes (two barrels, tip diameter 0.1-0.5 micron) have been developed for the measurement of acetylcholine, histamine, serotonin, and bile acid. Physiological and pathological models on the cellular or sub-cellular level have been established for the purpose of basic and clinical pharmacological research, treatment or diagnosis of certain diseases. The acetylcholine sensitive microelectrode has been applied to the study of acetylcholine activity in single erythrocytes of normal human subjects and patients suffering from manic depressive disorders. The bile acid selective microelectrode has been used for the direct measurement of intracellular bile acid activities both in colorectal cancer and colorectal mucosa in living condition.

Analysis of physiological and miRNA responses to Pi deficiency in alfalfa (Medicago sativa L.).

PubMed

Li, Zhenyi; Xu, Hongyu; Li, Yue; Wan, Xiufu; Ma, Zhao; Cao, Jing; Li, Zhensong; He, Feng; Wang, Yufei; Wan, Liqiang; Tong, Zongyong; Li, Xianglin

2018-03-01

The induction of miR399 and miR398 and the inhibition of miR156, miR159, miR160, miR171, miR2111, and miR2643 were observed under Pi deficiency in alfalfa. The miRNA-mediated genes involved in basic metabolic process, root and shoot development, stress response and Pi uptake. Inorganic phosphate (Pi) deficiency is known to be a limiting factor in plant development and growth. However, the underlying miRNAs associated with the Pi deficiency-responsive mechanism in alfalfa are unclear. To elucidate the molecular mechanism at the miRNA level, we constructed four small RNA (sRNA) libraries from the roots and shoots of alfalfa grown under normal or Pi-deficient conditions. In the present study, alfalfa plants showed reductions in biomass, photosynthesis, and Pi content and increases in their root-to-shoot ratio and citric, malic, and succinic acid contents under Pi limitation. Sequencing results identified 47 and 44 differentially expressed miRNAs in the roots and shoots, respectively. Furthermore, 909 potential target genes were predicted, and some targets were validated by RLM-RACE assays. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed prominent enrichment in signal transducer activity, binding and basic metabolic pathways for carbohydrates, fatty acids and amino acids; cellular response to hormone stimulus and response to auxin pathways were also enriched. qPCR results verified that the differentially expressed miRNA profile was consistent with sequencing results, and putative target genes exhibited opposite expression patterns. In this study, the miRNAs associated with the response to Pi limitation in alfalfa were identified. In addition, there was an enrichment of miRNA-targeted genes involved in biological regulatory processes such as basic metabolic pathways, root and shoot development, stress response, Pi transportation and citric acid secretion.

Fos metamorphoses: Lessons from mutants in model organisms (Drosophila).

PubMed

Alfonso-Gonzalez, Carlos; Riesgo-Escovar, Juan Rafael

2018-05-10

The Fos oncogene gene family is evolutionarily conserved throughout Eukarya. Fos proteins characteristically have a leucine zipper and a basic region with a helix-turn-helix motif that binds DNA. In vertebrates, there are several Fos homologs. They can homo- or hetero-dimerize via the leucine zipper domain. Fos homologs coupled with other transcription factors, like Jun oncoproteins, constitute the Activator Protein 1 (AP-1) complex. From its original inception as an oncogene, the subsequent finding that they act as transcription factors binding DNA sequences known as TRE, to the realization that they are activated in many different scenarios, and to loss-of-function analysis, the Fos proteins have traversed a multifarious path in development and physiology. They are instrumental in 'immediate early genes' responses, and activated by a seemingly myriad assemblage of different stimuli. Yet, the majority of these studies were basically gain-of-function studies, since it was thought that Fos genes would be cell lethal. Loss-of-function mutations in vertebrates were recovered later, and were not cell lethal. In fact, c-fos null mutations are viable with developmental defects (osteopetrosis and myeloid lineage abnormalities). It was then hypothesized that vertebrate genomes exhibit partial redundancy, explaining the 'mild' phenotypes, and complicating assessment of complete loss-of-function phenotypes. Due to its promiscuous activation, fos genes (especially c-fos) are now commonly used as markers for cellular responses to stimuli. fos homologs high sequence conservation (including Drosophila) is advantageous as it allows critical assessment of fos genes functions in this genetic model. Drosophila melanogaster contains only one fos homolog, the gene kayak. kayak mutations are lethal, and allow study of all the processes where fos is required. The kayak locus encodes several different isoforms, and is a pleiotropic gene variously required for development involving cell shape changes. In general, fos genes seem to primarily activate programs involved in cellular architectural rearrangements and cell shape changes. Copyright © 2018. Published by Elsevier B.V.

[Concept of optimal body composition of professional football players].

PubMed

Grigoryan, S

2011-09-01

Body composition and body weight are two of the many factors that contribute to optimal exercise performance. Body weight can influence an athlete's speed, endurance, and power, whereas body composition can affect an athlete's strength, agility, and appearance. Individualized assessment of an athlete's body composition and body weight or body image may be advantageous for the improvement of athletic performance. The purpose of the present research consists in development of physiologically proved modelling characteristic of high performance football players on the basis of the analysis of dynamics (changes) of the major parameters of structure of weight of football players of various ages in process of acquiring game experience and skill. 344 football players from 15 to 35 years old were surveyed. The basic parameters of body composition were determined. It was found that general tendency in dynamics of the basic components of structure of body composition at the end of playing season is expressed in appreciable gain of active cellular weight as analogue of the muscular mass, decrease in the absolute fat contents, increase in endocellular liquid and eritrocyte mass. Comparison of changeable parameters to external criteria of success in competition and tested productivity, adaptive reactions and stability of motivation led to the conclusion that quantitative sports-skill evaluation and forecast of the growth in achievements is possible.

Ligand-directed tosyl chemistry for in situ native protein labeling and engineering in living systems: from basic properties to applications.

PubMed

Tsukiji, Shinya; Hamachi, Itaru

2014-08-01

The ability to introduce any chemical probe to any endogenous target protein in its native environment, that is in cells and in vivo, is anticipated to provide various new exciting tools for biological and biomedical research. Although still at the prototype stage, the ligand-directed tosyl (LDT) chemistry is a novel type of affinity labeling technique that we developed for such a dream. This chemistry allows for modifying native proteins by various chemical probes with high specificity in various biological settings ranging from in vitro (in test tubes) to in living cells and in vivo. Since the first report, the list of proteins that are successfully labeled by the LDT chemistry has been increasing. A growing number of studies have demonstrated its utility to create semisynthetic proteins directly in cellular contexts. The in situ generated semisynthetic proteins are applicable for various types of analysis and imaging of intracellular biological processes. In this review, we summarize the basic properties of the LDT chemistry and its applications toward in situ engineering and analysis of native proteins in living systems. Current limitations and future challenges of this area are also described. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase.

PubMed

Jung, Gyung Ah; Shin, Bong Shik; Jang, Yeon Sue; Sohn, Jae Bum; Woo, Seon Rang; Kim, Jung Eun; Choi, Go; Lee, Kyung Mi; Min, Bon Hong; Lee, Kee Ho; Park, Gil Hong

2011-10-31

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)- p21Cip/WAF1 activation, and suppressed by the mitogenactivated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway.

Methylation of eukaryotic elongation factor 2 induced by basic fibroblast growth factor via mitogen-activated protein kinase

PubMed Central

Jung, Gyung Ah; Shin, Bong Shik; Jang, Yeon Sue; Sohn, Jae Bum; Woo, Seon Rang; Kim, Jung Eun; Choi, Go; Lee, Kyung-Mi; Min, Bon Hong

2011-01-01

Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblast NIH3T3 cells. The eEF2 methylation is preceded by ras-raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK1/2)-p21Cip/WAF1 activation, and suppressed by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and p21Cip/WAF1 short interfering RNA (siRNA). We determined that protein arginine methyltransferase 7 (PRMT7) is responsible for the methylation, and that PRMT5 acts as a coordinator. Collectively, we demonstrated that eEF2, a key factor involved in protein translational elongation is symmetrically arginine-methylated in a reversible manner, being regulated by bFGF through MAPK signaling pathway. PMID:21778808

Formation of the Embryonic Head in the Mouse: Attributes of a Gene Regulatory Network.

PubMed

Tam, Patrick P L; Fossat, Nicolas; Wilkie, Emilie; Loebel, David A F; Ip, Chi Kin; Ramialison, Mirana

2016-01-01

The embryonic head is the first major body part to be constructed during embryogenesis. The allocation and the assembly of the progenitor tissues, which start at gastrulation, are accompanied by the spatiotemporal activity of transcription factors and signaling pathways that drives lineage specification, germ layer formation, and cell/tissue movement. The morphogenesis, regionalization, and patterning of the brain and craniofacial structures rely on the function of LIM-domain, homeodomain, and basic helix-loop-helix transcription factors. These factors constitute the central nodes of a gene regulatory network (GRN) which encompasses and intersects with signaling pathways involved with head formation. It is predicted that the functional output of this "head GRN" impacts on cellular function and cell-cell interactions that are essential for lineage differentiation and tissue modeling, which are key processes underpinning the formation of the head. © 2016 Elsevier Inc. All rights reserved.

The binary protein-protein interaction landscape of Escherichia coli

PubMed Central

Rajagopala, Seesandra V.; Vlasblom, James; Arnold, Roland; Franca-Koh, Jonathan; Pakala, Suman B.; Phanse, Sadhna; Ceol, Arnaud; Häuser, Roman; Siszler, Gabriella; Wuchty, Stefan; Emili, Andrew; Babu, Mohan; Aloy, Patrick; Pieper, Rembert; Uetz, Peter

2014-01-01

Efforts to map the Escherichia coli interactome have identified several hundred macromolecular complexes, but direct binary protein-protein interactions (PPIs) have not been surveyed on a large scale. Here we performed yeast two-hybrid screens of 3,305 baits against 3,606 preys (~70% of the E. coli proteome) in duplicate to generate a map of 2,234 interactions, approximately doubling the number of known binary PPIs in E. coli. Integration of binary PPIs and genetic interactions revealed functional dependencies among components involved in cellular processes, including envelope integrity, flagellum assembly and protein quality control. Many of the binary interactions that could be mapped within multi-protein complexes were informative regarding internal topology and indicated that interactions within complexes are significantly more conserved than those interactions connecting different complexes. This resource will be useful for inferring bacterial gene function and provides a draft reference of the basic physical wiring network of this evolutionarily significant model microbe. PMID:24561554

Monoclonal antibodies for diagnosis and treatment.

PubMed

Dunn, D L

1993-11-01

One of the marvels of the host immune response is its response to antigenic foreign substances by manufacturing proteins that bind tenaciously to their targets. These proteins are antibodies or immunoglobulins produced in vast diversity during an individual's lifetime. By virtue of this process, the mammalian host possesses the innate ability to mount an initial response to antigens to which there has been no prior experience and to develop an even more effective response on reexposure to these same substances. This capacity to distinguish self from nonself is one of the most basic aspects of the cellular and humoral arms of the immune response and is one of the primary means by which the host combats infection caused by many different types of pathogens. In this context, antibodies have long been recognized as a critical component of host defenses and are capable of binding to invading microbes and microbial toxins.

Cortical Evolution: Judge the Brain by Its Cover

PubMed Central

Geschwind, Daniel H.; Rakic, Pasko

2014-01-01

To understand the emergence of human higher cognition, we must understand its biological substrate—the cerebral cortex, which considers itself the crowning achievement of evolution. Here, we describe how advances in developmental neurobiology, coupled with those in genetics, including adaptive protein evolution via gene duplications and the emergence of novel regulatory elements, can provide insights into the evolutionary mechanisms culminating in the human cerebrum. Given that the massive expansion of the cortical surface and elaboration of its connections in humans originates from developmental events, understanding the genetic regulation of cell number, neuronal migration to proper layers, columns, and regions, and ultimately their differentiation into specific phenotypes, is critical. The pre- and postnatal environment also interacts with the cellular substrate to yield a basic network that is refined via selection and elimination of synaptic connections, a process that is prolonged in humans. This knowledge provides essential insight into the pathogenesis of human-specific neuropsychiatric disorders. PMID:24183016

Nested effects models for learning signaling networks from perturbation data.

PubMed

Fröhlich, Holger; Tresch, Achim; Beissbarth, Tim

2009-04-01

Targeted gene perturbations have become a major tool to gain insight into complex cellular processes. In combination with the measurement of downstream effects via DNA microarrays, this approach can be used to gain insight into signaling pathways. Nested Effects Models were first introduced by Markowetz et al. as a probabilistic method to reverse engineer signaling cascades based on the nested structure of downstream perturbation effects. The basic framework was substantially extended later on by Fröhlich et al., Markowetz et al., and Tresch and Markowetz. In this paper, we present a review of the complete methodology with a detailed comparison of so far proposed algorithms on a qualitative and quantitative level. As an application, we present results on estimating the signaling network between 13 genes in the ER-alpha pathway of human MCF-7 breast cancer cells. Comparison with the literature shows a substantial overlap.

A real-time measurement system for parameters of live biology metabolism process with fiber optics

NASA Astrophysics Data System (ADS)

Tao, Wei; Zhao, Hui; Liu, Zemin; Cheng, Jinke; Cai, Rong

2010-08-01

Energy metabolism is one of the basic life activities of cellular in which lactate, O2 and CO2 will be released into the extracellular environment. By monitoring the quantity of these parameters, the mitochondrial performance will be got. A continuous measurement system for the concentration of O2, CO2 and PH value is introduced in this paper. The system is made up of several small-sized fiber optics biosensors corresponding to the container. The setup of the system and the principle of measurement of several parameters are explained. The setup of the fiber PH sensor based on principle of light absorption is also introduced in detail and some experimental results are given. From the results we can see that the system can measure the PH value precisely suitable for cell cultivation. The linear and repeatable accuracies are 3.6% and 6.7% respectively, which can fulfill the measurement task.

Growing Arabidopsis in vitro: cell suspensions, in vitro culture, and regeneration.

PubMed

Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar

2014-01-01

An understanding of basic methods in Arabidopsis tissue culture is beneficial for any laboratory working on this model plant. Tissue culture refers to the aseptic growth of cells, organs, or plants in a controlled environment, in which physical, nutrient, and hormonal conditions can all be easily manipulated and monitored. The methodology facilitates the production of a large number of plants that are genetically identical over a relatively short growth period. Techniques, including callus production, cell suspension cultures, and plant regeneration, are all indispensable tools for the study of cellular biochemical and molecular processes. Plant regeneration is a key technology for successful stable plant transformation, while cell suspension cultures can be exploited for metabolite profiling and mining. In this chapter we report methods for the successful and highly efficient in vitro regeneration of plants and production of stable cell suspension lines from leaf explants of both Arabidopsis thaliana and Arabidopsis halleri.

Biliary wound healing, ductular reactions, and IL-6/gp130 signaling in the development of liver disease

PubMed Central

Demetris, A J; III, John G Lunz; Specht, Susan; Nozaki, Isao

2006-01-01

Basic and translational wound healing research in the biliary tree lag significantly behind similar studies on the skin and gastrointestinal tract. This is at least partly attributable to lack of easy access to the biliary tract for study. But clinical relevance, more interest in biliary epithelial cell (BEC) pathophysiology, and widespread availability of BEC cultures are factors reversing this trend. In the extra-hepatic biliary tree, ineffectual wound healing, scarring and stricture development are pressing issues. In the smallest intra-hepatic bile ducts either impaired BEC proliferation or an exuberant response can contribute to liver disease. Chronic inflammation and persistent wound healing reactions in large and small bile ducts often lead to liver cancer. General concepts of wound healing as they apply to the biliary tract, importance of cellular processes dependent on IL-6/gp130/STAT3 signaling pathways, unanswered questions, and future directions are discussed. PMID:16773708

The role of the cell wall in fungal pathogenesis

PubMed Central

Arana, David M.; Prieto, Daniel; Román, Elvira; Nombela, César; Alonso‐Monge, Rebeca; Pla, Jesús

2009-01-01

Summary Fungal infections are a serious health problem. In recent years, basic research is focusing on the identification of fungal virulence factors as promising targets for the development of novel antifungals. The wall, as the most external cellular component, plays a crucial role in the interaction with host cells mediating processes such as adhesion or phagocytosis that are essential during infection. Specific components of the cell wall (called PAMPs) interact with specific receptors in the immune cell (called PRRs), triggering responses whose molecular mechanisms are being elucidated. We review here the main structural carbohydrate components of the fungal wall (glucan, mannan and chitin), how their biogenesis takes place in fungi and the specific receptors that they interact with. Different model fungal pathogens are chosen to illustrate the functional consequences of this interaction. Finally, the identification of the key components will have important consequences in the future and will allow better approaches to treat fungal infections. PMID:21261926

Emerging technology: applications of Raman spectroscopy for prostate cancer.

PubMed

Kast, Rachel E; Tucker, Stephanie C; Killian, Kevin; Trexler, Micaela; Honn, Kenneth V; Auner, Gregory W

2014-09-01

There is a need in prostate cancer diagnostics and research for a label-free imaging methodology that is nondestructive, rapid, objective, and uninfluenced by water. Raman spectroscopy provides a molecular signature, which can be scaled from micron-level regions of interest in cells to macroscopic areas of tissue. It can be used for applications ranging from in vivo or in vitro diagnostics to basic science laboratory testing. This work describes the fundamentals of Raman spectroscopy and complementary techniques including surface enhanced Raman scattering, resonance Raman spectroscopy, coherent anti-Stokes Raman spectroscopy, confocal Raman spectroscopy, stimulated Raman scattering, and spatially offset Raman spectroscopy. Clinical applications of Raman spectroscopy to prostate cancer will be discussed, including screening, biopsy, margin assessment, and monitoring of treatment efficacy. Laboratory applications including cell identification, culture monitoring, therapeutics development, and live imaging of cellular processes are discussed. Potential future avenues of research are described, with emphasis on multiplexing Raman spectroscopy with other modalities.

Protein–protein interactions and selection: yeast-based approaches that exploit guanine nucleotide-binding protein signaling.

PubMed

Ishii, Jun; Fukuda, Nobuo; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko

2010-05-01

For elucidating protein–protein interactions, many methodologies have been developed during the past two decades. For investigation of interactions inside cells under physiological conditions, yeast is an attractive organism with which to quickly screen for hopeful candidates using versatile genetic technologies, and various types of approaches are now available.Among them, a variety of unique systems using the guanine nucleotide-binding protein (G-protein) signaling pathway in yeast have been established to investigate the interactions of proteins for biological study and pharmaceutical research. G-proteins involved in various cellular processes are mainly divided into two groups: small monomeric G-proteins,and heterotrimeric G-proteins. In this minireview, we summarize the basic principles and applications of yeast-based screening systems, using these two types of G-protein, which are typically used for elucidating biological protein interactions but are differentiated from traditional yeast two-hybrid systems.

Footprint traversal by adenosine-triphosphate-dependent chromatin remodeler motor.

PubMed

Garai, Ashok; Mani, Jesrael; Chowdhury, Debashish

2012-04-01

Adenosine-triphosphate (ATP)-dependent chromatin remodeling enzymes (CREs) are biomolecular motors in eukaryotic cells. These are driven by a chemical fuel, namely, ATP. CREs actively participate in many cellular processes that require accessibility of specific segments of DNA which are packaged as chromatin. The basic unit of chromatin is a nucleosome where 146 bp ∼ 50 nm of a double-stranded DNA (dsDNA) is wrapped around a spool formed by histone proteins. The helical path of histone-DNA contact on a nucleosome is also called "footprint." We investigate the mechanism of footprint traversal by a CRE that translocates along the dsDNA. Our two-state model of a CRE captures effectively two distinct chemical (or conformational) states in the mechanochemical cycle of each ATP-dependent CRE. We calculate the mean time of traversal. Our predictions on the ATP dependence of the mean traversal time can be tested by carrying out in vitro experiments on mononucleosomes.

Scaling in geology: landforms and earthquakes.

PubMed Central

Turcotte, D L

1995-01-01

Landforms and earthquakes appear to be extremely complex; yet, there is order in the complexity. Both satisfy fractal statistics in a variety of ways. A basic question is whether the fractal behavior is due to scale invariance or is the signature of a broadly applicable class of physical processes. Both landscape evolution and regional seismicity appear to be examples of self-organized critical phenomena. A variety of statistical models have been proposed to model landforms, including diffusion-limited aggregation, self-avoiding percolation, and cellular automata. Many authors have studied the behavior of multiple slider-block models, both in terms of the rupture of a fault to generate an earthquake and in terms of the interactions between faults associated with regional seismicity. The slider-block models exhibit a remarkably rich spectrum of behavior; two slider blocks can exhibit low-order chaotic behavior. Large numbers of slider blocks clearly exhibit self-organized critical behavior. Images Fig. 6 PMID:11607562

Fracture Toughness Evaluation of Space Shuttle External Tank Thermal Protection System Polyurethane Foam Insulation Materials

NASA Technical Reports Server (NTRS)

McGill, Preston; Wells, Doug; Morgan, Kristin

2006-01-01

Experimental evaluation of the basic fracture properties of Thermal Protection System (TPS) polyurethane foam insulation materials was conducted to validate the methodology used in estimating critical defect sizes in TPS applications on the Space Shuttle External Fuel Tank. The polyurethane foam found on the External Tank (ET) is manufactured by mixing liquid constituents and allowing them to react and expand upwards - a process which creates component cells that are generally elongated in the foam rise direction and gives rise to mechanical anisotropy. Similarly, the application of successive foam layers to the ET produces cohesive foam interfaces (knitlines) which may lead to local variations in mechanical properties. This study reports the fracture toughness of BX-265, NCFI 24-124, and PDL-1034 closed-cell polyurethane foam as a function of ambient and cryogenic temperatures and knitline/cellular orientation at ambient pressure.

An Overview of Biofield Devices

PubMed Central

Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany

2015-01-01

Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of “biofield” interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or “subtle” processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine. PMID:26665041

An Overview of Biofield Devices.

PubMed

Muehsam, David; Chevalier, Gaétan; Barsotti, Tiffany; Gurfein, Blake T

2015-11-01

Advances in biophysics, biology, functional genomics, neuroscience, psychology, psychoneuroimmunology, and other fields suggest the existence of a subtle system of "biofield" interactions that organize biological processes from the subatomic, atomic, molecular, cellular, and organismic to the interpersonal and cosmic levels. Biofield interactions may bring about regulation of biochemical, cellular, and neurological processes through means related to electromagnetism, quantum fields, and perhaps other means of modulating biological activity and information flow. The biofield paradigm, in contrast to a reductionist, chemistry-centered viewpoint, emphasizes the informational content of biological processes; biofield interactions are thought to operate in part via low-energy or "subtle" processes such as weak, nonthermal electromagnetic fields (EMFs) or processes potentially related to consciousness and nonlocality. Biofield interactions may also operate through or be reflected in more well-understood informational processes found in electroencephalographic (EEG) and electrocardiographic (ECG) data. Recent advances have led to the development of a wide variety of therapeutic and diagnostic biofield devices, defined as physical instruments best understood from the viewpoint of a biofield paradigm. Here, we provide a broad overview of biofield devices, with emphasis on those devices for which solid, peer-reviewed evidence exists. A subset of these devices, such as those based upon EEG- and ECG-based heart rate variability, function via mechanisms that are well understood and are widely employed in clinical settings. Other device modalities, such a gas discharge visualization and biophoton emission, appear to operate through incompletely understood mechanisms and have unclear clinical significance. Device modes of operation include EMF-light, EMF-heat, EMF-nonthermal, electrical current, vibration and sound, physical and mechanical, intentionality and nonlocality, gas and plasma, and other (mode of operation not well-understood). Methodological issues in device development and interfaces for future interdisciplinary research are discussed. Devices play prominent cultural and scientific roles in our society, and it is likely that device technologies will be one of the most influential access points for the furthering of biofield research and the dissemination of biofield concepts. This developing field of study presents new areas of research that have many important implications for both basic science and clinical medicine.

Melt-processed polymeric cellular dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2015-12-28

The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

A Simple Microscopy Assay to Teach the Processes of Phagocytosis and Exocytosis

ERIC Educational Resources Information Center

Gray, Ross; Gray, Andrew; Fite, Jessica L.; Jordan, Renee; Stark, Sarah; Naylor, Kari

2012-01-01

Phagocytosis and exocytosis are two cellular processes involving membrane dynamics. While it is easy to understand the purpose of these processes, it can be extremely difficult for students to comprehend the actual mechanisms. As membrane dynamics play a significant role in many cellular processes ranging from cell signaling to cell division to…

Biotechnologies as a Context for Enhancing Junior High-School Students' Ability to Ask Meaningful Questions about Abstract Biological Processes.

ERIC Educational Resources Information Center

Olsher, G.; Dreyfus, A.

1999-01-01

Suggests a new approach to teaching about biochemical cellular processes by stimulating student interest in those biochemical processes that allowed for the outcomes of modern biotechnologies. Discusses the development of students' ability to ask meaningful questions about intra-cellular processes, and the resulting meaningful learning of relevant…

Molecular and genetic characterization of osmosensing and signal transduction in the nematode Caenorhabditis elegans.

PubMed

Choe, Keith P; Strange, Kevin

2007-11-01

Osmotic homeostasis is a fundamental requirement for life. In general, the effector mechanisms that mediate cellular and extracellular osmoregulation in animals are reasonably well defined. However, at the molecular level, little is known about how animals detect osmotic and ionic perturbations and transduce them into regulatory responses. The nematode Caenorhabditis elegans provides numerous powerful experimental advantages for defining the genes and integrated gene networks that underlie basic biological processes. These advantages include a fully sequenced and well-annotated genome, forward and reverse genetic and molecular tractability, and a relatively simple anatomy. C. elegans normally inhabits soil environments where it is exposed to repeated osmotic stress. In the laboratory, nematodes readily acclimate to and recover from extremes of hypertonicity. We review recent progress in defining the molecular mechanisms that underlie osmosensing and associated signal transduction in C. elegans. Some of these mechanisms are now known to be highly conserved. Therefore, studies of osmosensing in nematodes have provided, and will undoubtedly continue to provide, new insights into similar processes in more complex organisms including mammals.

Yeast as a model for Ras signalling.

PubMed

Tisi, Renata; Belotti, Fiorella; Martegani, Enzo

2014-01-01

For centuries yeast species have been popular hosts for classical biotechnology processes, such as baking, brewing, and wine making, and more recently for recombinant proteins production, thanks to the advantages of unicellular organisms (i.e., ease of genetic manipulation and rapid growth) together with the ability to perform eukaryotic posttranslational modifications. Moreover, yeast cells have been used for few decades as a tool for identifying the genes and pathways involved in basic cellular processes such as the cell cycle, aging, and stress response. In the budding yeast S. cerevisiae the Ras/cAMP/PKA pathway is directly involved in the regulation of metabolism, cell growth, stress resistance, and proliferation in response to the availability of nutrients and in the adaptation to glucose, controlling cytosolic cAMP levels and consequently the cAMP-dependent protein kinase (PKA) activity. Moreover, Ras signalling has been identified in several pathogenic yeasts as a key controller for virulence, due to its involvement in yeast morphogenesis. Nowadays, yeasts are still useful for Ras-like proteins investigation, both as model organisms and as a test tube to study variants of heterologous Ras-like proteins.

Overview of ENEA's Projects on lithium batteries

NASA Astrophysics Data System (ADS)

Alessandrini, F.; Conte, M.; Passerini, S.; Prosini, P. P.

The increasing need of high performance batteries in various small-scale and large-scale applications (portable electronics, notebooks, palmtops, cellular phones, electric vehicles, UPS, load levelling) in Italy is motivating the R&D efforts of various public and private organizations. Research of lithium batteries in Italy goes back to the beginning of the technological development of primary and secondary lithium systems with national know-how spread in various academic and public institutions with a few private stakeholders. In the field of lithium polymer batteries, ENEA has been dedicating significant efforts in almost two decades to promote and carry out basic R&D and pre-industrial development projects. In recent years, three major national projects have been performed and coordinated by ENEA in co-operation with some universities, governmental research organizations and industry. In these projects novel polymer electrolytes with ceramic additives, low cost manganese oxide-based composite cathodes, environmentally friendly process for polymer electrolyte, fabrication processes of components and cells have been investigated and developed in order to fulfill long-term needs of cost-effective and highly performant lithium polymer batteries.

Thermal injury models for optical treatment of biological tissues: a comparative study.

PubMed

Fanjul-Velez, Felix; Ortega-Quijano, Noe; Salas-Garcia, Irene; Arce-Diego, Jose L

2010-01-01

The interaction of optical radiation with biological tissues causes an increase in the temperature that, depending on its magnitude, can provoke a thermal injury process in the tissue. The establishment of laser irradiation pathological limits constitutes an essential task, as long as it enables to fix and delimit a range of parameters that ensure a safe treatment in laser therapies. These limits can be appropriately described by kinetic models of the damage processes. In this work, we present and compare several models for the study of thermal injury in biological tissues under optical illumination, particularly the Arrhenius thermal damage model and the thermal dosimetry model based on CEM (Cumulative Equivalent Minutes) 43°C. The basic concepts that link the temperature and exposition time with the tissue injury or cellular death are presented, and it will be shown that they enable to establish predictive models for the thermal damage in laser therapies. The results obtained by both models will be compared and discussed, highlighting the main advantages of each one and proposing the most adequate one for optical treatment of biological tissues.

Modes of fossil preservation

USGS Publications Warehouse

Schopf, J.M.

1975-01-01

The processes of geologic preservation are important for understanding the organisms represented by fossils. Some fossil differences are due to basic differences in organization of animals and plants, but the interpretation of fossils has also tended to be influenced by modes of preservation. Four modes of preservation generally can be distinguished: (1) Cellular permineralization ("petrifaction") preserves anatomical detail, and, occasionally, even cytologic structures. (2) Coalified compression, best illustrated by structures from coal but characteristic of many plant fossils in shale, preserves anatomical details in distorted form and produces surface replicas (impressions) on enclosing matrix. (3) Authigenic preservation replicates surface form or outline (molds and casts) prior to distortion by compression and, depending on cementation and timing, may intergrade with fossils that have been subject to compression. (4) Duripartic (hard part) preservation is characteristic of fossil skeletal remains, predominantly animal. Molds, pseudomorphs, or casts may form as bulk replacements following dissolution of the original fossil material, usually by leaching. Classification of the kinds of preservation in fossils will aid in identifying the processes responsible for modifying the fossil remains of both animals and plants. ?? 1975.

Analyzing the dynamics of cell cycle processes from fixed samples through ergodic principles

PubMed Central

Wheeler, Richard John

2015-01-01

Tools to analyze cyclical cellular processes, particularly the cell cycle, are of broad value for cell biology. Cell cycle synchronization and live-cell time-lapse observation are widely used to analyze these processes but are not available for many systems. Simple mathematical methods built on the ergodic principle are a well-established, widely applicable, and powerful alternative analysis approach, although they are less widely used. These methods extract data about the dynamics of a cyclical process from a single time-point “snapshot” of a population of cells progressing through the cycle asynchronously. Here, I demonstrate application of these simple mathematical methods to analysis of basic cyclical processes—cycles including a division event, cell populations undergoing unicellular aging, and cell cycles with multiple fission (schizogony)—as well as recent advances that allow detailed mapping of the cell cycle from continuously changing properties of the cell such as size and DNA content. This includes examples using existing data from mammalian, yeast, and unicellular eukaryotic parasite cell biology. Through the ongoing advances in high-throughput cell analysis by light microscopy, electron microscopy, and flow cytometry, these mathematical methods are becoming ever more important and are a powerful complementary method to traditional synchronization and time-lapse cell cycle analysis methods. PMID:26543196

COBRApy: COnstraints-Based Reconstruction and Analysis for Python.

PubMed

Ebrahim, Ali; Lerman, Joshua A; Palsson, Bernhard O; Hyduke, Daniel R

2013-08-08

COnstraint-Based Reconstruction and Analysis (COBRA) methods are widely used for genome-scale modeling of metabolic networks in both prokaryotes and eukaryotes. Due to the successes with metabolism, there is an increasing effort to apply COBRA methods to reconstruct and analyze integrated models of cellular processes. The COBRA Toolbox for MATLAB is a leading software package for genome-scale analysis of metabolism; however, it was not designed to elegantly capture the complexity inherent in integrated biological networks and lacks an integration framework for the multiomics data used in systems biology. The openCOBRA Project is a community effort to promote constraints-based research through the distribution of freely available software. Here, we describe COBRA for Python (COBRApy), a Python package that provides support for basic COBRA methods. COBRApy is designed in an object-oriented fashion that facilitates the representation of the complex biological processes of metabolism and gene expression. COBRApy does not require MATLAB to function; however, it includes an interface to the COBRA Toolbox for MATLAB to facilitate use of legacy codes. For improved performance, COBRApy includes parallel processing support for computationally intensive processes. COBRApy is an object-oriented framework designed to meet the computational challenges associated with the next generation of stoichiometric constraint-based models and high-density omics data sets. http://opencobra.sourceforge.net/

Comparison of infrared and 3D digital image correlation techniques applied for mechanical testing of materials

NASA Astrophysics Data System (ADS)

Krstulović-Opara, Lovre; Surjak, Martin; Vesenjak, Matej; Tonković, Zdenko; Kodvanj, Janoš; Domazet, Željko

2015-11-01

To investigate the applicability of infrared thermography as a tool for acquiring dynamic yielding in metals, a comparison of infrared thermography with three dimensional digital image correlation has been made. Dynamical tension tests and three point bending tests of aluminum alloys have been performed to evaluate results obtained by IR thermography in order to detect capabilities and limits for these two methods. Both approaches detect pastification zone migrations during the yielding process. The results of the tension test and three point bending test proved the validity of the IR approach as a method for evaluating the dynamic yielding process when used on complex structures such as cellular porous materials. The stability of the yielding process in the three point bending test, as contrary to the fluctuation of the plastification front in the tension test, is of great importance for the validation of numerical constitutive models. The research proved strong performance, robustness and reliability of the IR approach when used to evaluate yielding during dynamic loading processes, while the 3D DIC method proved to be superior in the low velocity loading regimes. This research based on two basic tests, proved the conclusions and suggestions presented in our previous research on porous materials where middle wave infrared thermography was applied.

Workbook, Basic Mathematics and Wastewater Processing Calculations.

ERIC Educational Resources Information Center

New York State Dept. of Environmental Conservation, Albany.

This workbook serves as a self-learning guide to basic mathematics and treatment plant calculations and also as a reference and source book for the mathematics of sewage treatment and processing. In addition to basic mathematics, the workbook discusses processing and process control, laboratory calculations and efficiency calculations necessary in…

Mitochondrial correlates of signaling processes involved with the cellular response to eimeria infection in broiler chickens

USDA-ARS?s Scientific Manuscript database

Host cellular responses to coccidiosis infection are consistent with elements of apoptosis, autophagy, and necrosis. These processes are enhanced in the cell through cell-directed signaling or repressed through parasite-derived inhibitors of these processes favoring the survival of the parasite. Acr...

Cell death during the postnatal morphogenesis of the normal rabbit kidney and in experimental renal polycystosis.

PubMed Central

García-Porrero, J A; Ojeda, J L; Hurlé, J M

1978-01-01

We have studied, by means of optic and electron microscopy, the normal and abnormal cell death that takes place during the postnatal morphogenesis of rabbit kidney, and in the experimental renal polycystosis produced by methylprednisolone acetate. In the normal kidney intertubular cell death can be observed during the first 20 days of the postnatal development. However, cell death in the normal metanephric blastema is a very rare event. In the polycystic kidney numerous dead cells can be seen between the third and forty eighth days after injection. The topography and morphology of the dead cells depend on the stage in the evolution of the disease. In the 'stage of renal immaturity', dying and dead cells are present in the nephrogenic tissue, in the dilating collecting tubules and in the intertubular spaces. In this stage the cellular pathology is essentially nuclear. In the stage of tubular cysts, the dead cells are mostly located in the walls of cysts, with some dead cells, but mostly cellular debris in their lumina. At this stage the cellular pathology is basically cytoplasmic. The dead cells are eventually digested by what appear to be phagocytes of tubular epithelial origin. It is suggested that cell death is an important factor in the evolution of the lesions of renal polycystosis induced by corticosteroids, and probably in the initiation of the pathological process as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 PMID:670065

European Seminar on Neural Computing

DTIC Science & Technology

1988-08-31

elements can be fabricated on a single chip . Two specific oriented language (for example, SMALLTALK or cellular arrays, namely, the programmable systolic... chip POOL) the basic concepts are: objects are viewed as (Fisher, 1983) and the connection machine (Treleaven, active, they may contain state, and...flow computer the availability of 1. Programmable Systolic Chip . Programmable Sys- input operands triggers the execution of the instruction tolic Chips

Wnt signaling and osteoporosis

PubMed Central

Manolagas, Stavros C.

2014-01-01

Major advances in understanding basic bone biology and the cellular and molecular mechanisms responsible for the development of osteoporosis, over the last 20 years, have dramatically altered the management of this disease. The purpose of this mini-review is to highlight the seminal role of Wnt signaling in bone homeostasis and disease and the emergence of novel osteoporosis therapies by targeting Wnt signaling with drugs. PMID:24815296

Comparative Tissue Stainability of Lawsonia inermis (Henna) and Eosin as Counterstains to Hematoxylin in Brain Tissues.

PubMed

Alawa, Judith N; Gideon, Gbenga O; Adetiba, Bamidele; Alawa, Clement B

2015-04-01

We hyposthesized that henna staining could provide an alternative to eosin when used as a counterstain to hematoxylin for understanding basic neurohistological principles. Therefore, this study was aimed at investigating the suitability of henna as counterstain to hematoxylin for the demonstration of the layer stratification and cellular distribution in the brain tissue. Henna stained nervous tissue by reacting with the basic elements in proteins via its amino groups. It stained the neuropil and connective tissue membranes brown and effectively outlined the perikarya of neurons with no visible nuclei demonstrating that it is an acidic dye. Henna as a counterstain to hematoxylin demonstrated reliability as a new neurohistological stain. It facilitated identification of cortical layer stratification and cellular distribution in brain tissue sections from Wistar rats. This was comparable to standard hematoxylin and eosin staining as morphological and morphometrical analyses of stained cells did not show significant differences in size or number. This study presents a method for staining with henna and demonstrates that although henna and eosin belong to different dye groups (anthraquinone and xanthenes, respectively) based on their chromophores, they share similar staining techniques and thus could be used interchangeably in neurohistology.

Light Weight Biomorphous Cellular Ceramics from Cellulose Templates

NASA Technical Reports Server (NTRS)

Singh, Mrityunjay; Yee, Bo-Moon; Gray, Hugh R. (Technical Monitor)

2003-01-01

Bimorphous ceramics are a new class of materials that can be fabricated from the cellulose templates derived from natural biopolymers. These biopolymers are abundantly available in nature and are produced by the photosynthesis process. The wood cellulose derived carbon templates have three- dimensional interconnectivity. A wide variety of non-oxide and oxide based ceramics have been fabricated by template conversion using infiltration and reaction-based processes. The cellular anatomy of the cellulose templates plays a key role in determining the processing parameters (pyrolysis, infiltration conditions, etc.) and resulting ceramic materials. The processing approach, microstructure, and mechanical properties of the biomorphous cellular ceramics (silicon carbide and oxide based) have been discussed.

Model-based design of experiments for cellular processes.

PubMed

Chakrabarty, Ankush; Buzzard, Gregery T; Rundell, Ann E

2013-01-01

Model-based design of experiments (MBDOE) assists in the planning of highly effective and efficient experiments. Although the foundations of this field are well-established, the application of these techniques to understand cellular processes is a fertile and rapidly advancing area as the community seeks to understand ever more complex cellular processes and systems. This review discusses the MBDOE paradigm along with applications and challenges within the context of cellular processes and systems. It also provides a brief tutorial on Fisher information matrix (FIM)-based and Bayesian experiment design methods along with an overview of existing software packages and computational advances that support MBDOE application and adoption within the Systems Biology community. As cell-based products and biologics progress into the commercial sector, it is anticipated that MBDOE will become an essential practice for design, quality control, and production. Copyright © 2013 Wiley Periodicals, Inc.

SIRTUIN 1 AND SIRTUIN 3: PHYSIOLOGICAL MODULATORS OF METABOLISM

PubMed Central

Nogueiras, Ruben; Habegger, Kirk M.; Chaudhary, Nilika; Finan, Brian; Banks, Alexander S.; Dietrich, Marcelo O.; Horvath, Tamas L.; Sinclair, David A.; Pfluger, Paul T.; Tschöop, Matthias H.

2013-01-01

The sirtuins are a family of highly conserved NAD+-dependent deacetylases that act as cellular sensors to detect energy availability and modulate metabolic processes. Two sirtuins that are central to the control of metabolic processes are mammalian sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), which are localized to the nucleus and mitochondria, respectively. Both are activated by high NAD+ levels, a condition caused by low cellular energy status. By deacetylating a variety of proteins that induce catabolic processes while inhibiting anabolic processes, SIRT1 and SIRT3 coordinately increase cellular energy stores and ultimately maintain cellular energy homeostasis. Defects in the pathways controlled by SIRT1 and SIRT3 are known to result in various metabolic disorders. Consequently, activation of sirtuins by genetic or pharmacological means can elicit multiple metabolic benefits that protect mice from diet-induced obesity, type 2 diabetes, and nonalcoholic fatty liver disease. PMID:22811431

Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits

PubMed Central

Tirone, Felice; Farioli-Vecchioli, Stefano; Micheli, Laura; Ceccarelli, Manuela; Leonardi, Luca

2013-01-01

Within the hippocampal circuitry, the basic function of the dentate gyrus is to transform the memory input coming from the enthorinal cortex into sparse and categorized outputs to CA3, in this way separating related memory information. New neurons generated in the dentate gyrus during adulthood appear to facilitate this process, allowing a better separation between closely spaced memories (pattern separation). The evidence underlying this model has been gathered essentially by ablating the newly adult-generated neurons. This approach, however, does not allow monitoring of the integration of new neurons into memory circuits and is likely to set in motion compensatory circuits, possibly leading to an underestimation of the role of new neurons. Here we review the background of the basic function of the hippocampus and of the known properties of new adult-generated neurons. In this context, we analyze the cognitive performance in mouse models generated by us and others, with modified expression of the genes Btg2 (PC3/Tis21), Btg1, Pten, BMP4, etc., where new neurons underwent a change in their differentiation rate or a partial decrease of their proliferation or survival rate rather than ablation. The effects of these modifications are equal or greater than full ablation, suggesting that the architecture of circuits, as it unfolds from the interaction between existing and new neurons, can have a greater functional impact than the sheer number of new neurons. We propose a model which attempts to measure and correlate the set of cellular changes in the process of neurogenesis with the memory function. PMID:23734097

Computational modeling of the human auditory periphery: Auditory-nerve responses, evoked potentials and hearing loss.

PubMed

Verhulst, Sarah; Altoè, Alessandro; Vasilkov, Viacheslav

2018-03-01

Models of the human auditory periphery range from very basic functional descriptions of auditory filtering to detailed computational models of cochlear mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal processing. It is challenging to include detailed physiological descriptions of cellular components into human auditory models because single-cell data stems from invasive animal recordings while human reference data only exists in the form of population responses (e.g., otoacoustic emissions, auditory evoked potentials). To embed physiological models within a comprehensive human auditory periphery framework, it is important to capitalize on the success of basic functional models of hearing and render their descriptions more biophysical where possible. At the same time, comprehensive models should capture a variety of key auditory features, rather than fitting their parameters to a single reference dataset. In this study, we review and improve existing models of the IHC-AN complex by updating their equations and expressing their fitting parameters into biophysical quantities. The quality of the model framework for human auditory processing is evaluated using recorded auditory brainstem response (ABR) and envelope-following response (EFR) reference data from normal and hearing-impaired listeners. We present a model with 12 fitting parameters from the cochlea to the brainstem that can be rendered hearing impaired to simulate how cochlear gain loss and synaptopathy affect human population responses. The model description forms a compromise between capturing well-described single-unit IHC and AN properties and human population response features. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Taste transductions in taste receptor cells: basic tastes and moreover.

PubMed

Iwata, Shusuke; Yoshida, Ryusuke; Ninomiya, Yuzo

2014-01-01

In the oral cavity, taste receptor cells dedicate to detecting chemical compounds in foodstuffs and transmitting their signals to gustatory nerve fibers. Heretofore, five taste qualities (sweet, umami, bitter, salty and sour) are generally accepted as basic tastes. Each of these may have a specific role in the detection of nutritious and poisonous substances; sweet for carbohydrate sources of calories, umami for protein and amino acid contents, bitter for harmful compounds, salty for minerals and sour for ripeness of fruits and spoiled foods. Recent studies have revealed molecular mechanisms for reception and transduction of these five basic tastes. Sweet, umami and bitter tastes are mediated by G-protein coupled receptors (GPCRs) and second-messenger signaling cascades. Salty and sour tastes are mediated by channel-type receptors. In addition to five basic tastes, taste receptor cells may have the ability to detect fat taste, which is elicited by fatty acids, and calcium taste, which is elicited by calcium. Taste compounds eliciting either fat taste or calcium taste may be detected by specific GPCRs expressed in taste receptor cells. This review will focus on transduction mechanisms and cellular characteristics responsible for each of basic tastes, fat taste and calcium taste.

RNA sequencing of chorionic villi from recurrent pregnancy loss patients reveals impaired function of basic nuclear and cellular machinery

PubMed Central

Sõber, Siim; Rull, Kristiina; Reiman, Mario; Ilisson, Piret; Mattila, Pirkko; Laan, Maris

2016-01-01

Recurrent pregnancy loss (RPL) concerns ~3% of couples aiming at childbirth. In the current study, transcriptomes and miRNomes of 1st trimester placental chorionic villi were analysed for 2 RPL cases (≥6 miscarriages) and normal, but electively terminated pregnancies (ETP; n = 8). Sequencing was performed on Illumina HiSeq 2000 platform. Differential expression analyses detected 51 (27%) transcripts with increased and 138 (73%) with decreased expression in RPL compared to ETP (DESeq: FDR P < 0.1 and DESeq2: <0.05). RPL samples had substantially decreased transcript levels of histones, regulatory RNAs and genes involved in telomere, spliceosome, ribosomal, mitochondrial and intra-cellular signalling functions. Downregulated expression of HIST1H1B and HIST1H4A (Wilcoxon test, fc≤0.372, P≤9.37 × 10−4) was validated in an extended sample by quantitative PCR (RPL, n = 14; ETP, n = 24). Several upregulated genes are linked to placental function and pregnancy complications: ATF4, C3, PHLDA2, GPX4, ICAM1, SLC16A2. Analysis of the miRNA-Seq dataset identified no large disturbances in RPL samples. Notably, nearly 2/3 of differentially expressed genes have binding sites for E2F transcription factors, coordinating mammalian endocycle and placental development. For a conceptus destined to miscarriage, the E2F TF-family represents a potential key coordinator in reprogramming the placental genome towards gradually stopping the maintenance of basic nuclear and cellular functions. PMID:27929073

Structural Basis of a Thiol-Disulfide Oxidoreductase in the Hedgehog-Forming Actinobacterium Corynebacterium matruchotii.

PubMed

Luong, Truc Thanh; Tirgar, Reyhaneh; Reardon-Robinson, Melissa E; Joachimiak, Andrzej; Osipiuk, Jerzy; Ton-That, Hung

2018-05-01

The actinobacterium Corynebacterium matruchotii has been implicated in nucleation of oral microbial consortia leading to biofilm formation. Due to the lack of genetic tools, little is known about basic cellular processes, including protein secretion and folding, in this organism. We report here a survey of the C. matruchotii genome, which encodes a large number of exported proteins containing paired cysteine residues, and identified an oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA (MdbA Cd ). Crystallization studies uncovered that the 1.2-Å resolution structure of C. matruchotii MdbA (MdbA Cm ) possesses two conserved features found in actinobacterial MdbA enzymes, a thioredoxin-like fold and an extended α-helical domain. By reconstituting the disulfide bond-forming machine in vitro , we demonstrated that MdbA Cm catalyzes disulfide bond formation within the actinobacterial pilin FimA. A new gene deletion method supported that mdbA is essential in C. matruchotii Remarkably, heterologous expression of MdbA Cm in the C. diphtheriae Δ mdbA mutant rescued its known defects in cell growth and morphology, toxin production, and pilus assembly, and this thiol-disulfide oxidoreductase activity required the catalytic motif CXXC. Altogether, the results suggest that MdbA Cm is a major thiol-disulfide oxidoreductase, which likely mediates posttranslocational protein folding in C. matruchotii by a mechanism that is conserved in Actinobacteria IMPORTANCE The actinobacterium Corynebacterium matruchotii has been implicated in the development of oral biofilms or dental plaque; however, little is known about the basic cellular processes in this organism. We report here a high-resolution structure of a C. matruchotii oxidoreductase that is highly homologous to the Corynebacterium diphtheriae thiol-disulfide oxidoreductase MdbA. By biochemical analysis, we demonstrated that C. matruchotii MdbA catalyzes disulfide bond formation in vitro Furthermore, a new gene deletion method revealed that deletion of mdbA is lethal in C. matruchotii Remarkably, C. matruchotii MdbA can replace C. diphtheriae MdbA to maintain normal cell growth and morphology, toxin production, and pilus assembly. Overall, our studies support the hypothesis that C. matruchotii utilizes MdbA as a major oxidoreductase to catalyze oxidative protein folding. Copyright © 2018 American Society for Microbiology.

AGCVIII Kinases: at the crossroads of cellular signaling

USDA-ARS?s Scientific Manuscript database

AGCVIII kinases regulate diverse developmental and cellular processes in plants. As putative mediators of secondary messengers, AGCVIII kinases potentially integrate developmental and environmental cues into specific cellular responses through substrate phosphorylation. Here we discuss the functiona...

Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

PubMed

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

2010-02-01

The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell biology has advanced rapidly with increasing availability of new data and powerful simulation techniques, a quantitative orientation is still lacking in life sciences education to make efficient use of these new tools to implement the new toxicity testing paradigm. A revamped undergraduate curriculum in the biological sciences including compulsory courses in mathematics and analysis of dynamical systems is required to address this gap. In parallel, dissemination of computational systems biology techniques and other analytical tools among practicing toxicologists and risk assessment professionals will help accelerate implementation of the new toxicity testing vision.

Design and testing of botanical thermotropic actuator mechanisms in thermally adaptive building coverings

NASA Astrophysics Data System (ADS)

Barrett, Ronald M.; Barrett, Ronald P.; Barrett, Cassandra M.

2017-09-01

This paper lays out the inspiration, operational principles, analytical modeling and coupon testing of a new class of thermally adaptive building coverings. The fundamental driving concepts for these coverings are derived from various families of thermotropic plant structures. Certain plant cellular structures like those in Mimosa pudica (Sensitive Plant), Rhododendron leaves or Albizia julibrissin (Mimosa Tree), exhibit actuation physiology which depends on changes in cellular turgor pressures to generate motion. This form of cellular action via turgor pressure manipulation is an inspiration for a new field of thermally adaptive building coverings which use various forms of cellular foam to aid or enable actuation much like plant cells are used to move leaves. When exposed to high solar loading, the structures use the inherent actuation capability of pockets of air trapped in closed cell foam as actuators to curve plates upwards and outwards. When cold, these same structures curve back towards the building forming large convex pockets of dead air to insulate the building. This paper describes basic classical laminated plate theory models comparing theory and experiment of such coupons containing closed-cell foam actuators. The study concludes with a global description of the effectiveness of this class of thermally adaptive building coverings.

Differential growth of wrinkled biofilms

NASA Astrophysics Data System (ADS)

Espeso, D. R.; Carpio, A.; Einarsson, B.

2015-02-01

Biofilms are antibiotic-resistant bacterial aggregates that grow on moist surfaces and can trigger hospital-acquired infections. They provide a classical example in biology where the dynamics of cellular communities may be observed and studied. Gene expression regulates cell division and differentiation, which affect the biofilm architecture. Mechanical and chemical processes shape the resulting structure. We gain insight into the interplay between cellular and mechanical processes during biofilm development on air-agar interfaces by means of a hybrid model. Cellular behavior is governed by stochastic rules informed by a cascade of concentration fields for nutrients, waste, and autoinducers. Cellular differentiation and death alter the structure and the mechanical properties of the biofilm, which is deformed according to Föppl-Von Kármán equations informed by cellular processes and the interaction with the substratum. Stiffness gradients due to growth and swelling produce wrinkle branching. We are able to reproduce wrinkled structures often formed by biofilms on air-agar interfaces, as well as spatial distributions of differentiated cells commonly observed with B. subtilis.

Laboratory and clinical studies of cancer chemoprevention by antioxidants in berries.

PubMed

Stoner, Gary David; Wang, Li-Shu; Casto, Bruce Cordell

2008-09-01

Reactive oxygen species (ROS) are a major cause of cellular injury in an increasing number of diseases, including cancer. Most ROS are created in the cell through normal cellular metabolism. They can be produced by environmental insults such as ultraviolet light and toxic chemicals, as well as by the inflammatory process. Interception of ROS or limiting their cellular effects is a major role of antioxidants. Due to their content of phenolic and flavonoid compounds, berries exhibit high antioxidant potential, exceeding that of many other foodstuffs. Through their ability to scavenge ROS and reduce oxidative DNA damage, stimulate antioxidant enzymes, inhibit carcinogen-induced DNA adduct formation and enhance DNA repair, berry compounds have been shown to inhibit mutagenesis and cancer initiation. Berry constituents also influence cellular processes associated with cancer progression including signaling pathways associated with cell proliferation, differentiation, apoptosis and angiogenesis. This review article summarizes laboratory and human studies, demonstrating the protective effects of berries and berry constituents on oxidative and other cellular processes leading to cancer development.

Laboratory and clinical studies of cancer chemoprevention by antioxidants in berries

PubMed Central

Stoner, Gary David; Wang, Li-Shu; Casto, Bruce Cordell

2008-01-01

Reactive oxygen species (ROS) are a major cause of cellular injury in an increasing number of diseases, including cancer. Most ROS are created in the cell through normal cellular metabolism. They can be produced by environmental insults such as ultraviolet light and toxic chemicals, as well as by the inflammatory process. Interception of ROS or limiting their cellular effects is a major role of antioxidants. Due to their content of phenolic and flavonoid compounds, berries exhibit high antioxidant potential, exceeding that of many other foodstuffs. Through their ability to scavenge ROS and reduce oxidative DNA damage, stimulate antioxidant enzymes, inhibit carcinogen-induced DNA adduct formation and enhance DNA repair, berry compounds have been shown to inhibit mutagenesis and cancer initiation. Berry constituents also influence cellular processes associated with cancer progression including signaling pathways associated with cell proliferation, differentiation, apoptosis and angiogenesis. This review article summarizes laboratory and human studies, demonstrating the protective effects of berries and berry constituents on oxidative and other cellular processes leading to cancer development. PMID:18544560

Nanotechnology research: applications in nutritional sciences.

PubMed

Srinivas, Pothur R; Philbert, Martin; Vu, Tania Q; Huang, Qingrong; Kokini, Josef L; Saltos, Etta; Saos, Etta; Chen, Hongda; Peterson, Charles M; Friedl, Karl E; McDade-Ngutter, Crystal; Hubbard, Van; Starke-Reed, Pamela; Miller, Nancy; Betz, Joseph M; Dwyer, Johanna; Milner, John; Ross, Sharon A

2010-01-01

The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of approximately 1-100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled "Nanotechnology Research: Applications in Nutritional Sciences" was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities.

Mechanisms of lung aging.

PubMed

Brandenberger, Christina; Mühlfeld, Christian

2017-03-01

Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth. Hallmarks of aging include alterations at molecular, cellular and cell-cell interaction levels. Because of the great variety of cell types in the lung, the consequences of aging display a broad spectrum of phenotypes. For example, aging is associated with more collagen and less elastin production by fibroblasts, thus increasing pulmonary stiffness and lowering compliance. Decreased sympathetic airway innervation may increase the constriction status of airway smooth muscle cells. Aging of resident and systemic immune cells leads to a pro-inflammatory milieu and reduced capacity of fighting infectious diseases. The current review provides an overview of cellular changes occurring with advancing age in general and in several cell types of the lung as well as of the immune system. Thereby, this survey not only aims at providing a better understanding of the mechanisms of pulmonary aging but also to identify gaps in knowledge that warrant further investigations.

Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function12

PubMed Central

Millar, Courtney L; Duclos, Quinn

2017-01-01

Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function. PMID:28298268

Hybrid proline-rich proteins: novel players in plant cell elongation?

PubMed Central

Dvořáková, Lenka; Srba, Miroslav; Opatrny, Zdenek; Fischer, Lukas

2012-01-01

Background and Aims Hybrid proline-rich proteins (HyPRPs) represent a large family of putative cell-wall proteins characterized by the presence of a variable N-terminal domain and a conserved C-terminal domain that is related to non-specific lipid transfer proteins. The function of HyPRPs remains unclear, but their widespread occurrence and abundant expression patterns indicate that they may be involved in a basic cellular process. Methods To elucidate the cellular function of HyPRPs, we modulated the expression of three HyPRP genes in tobacco (Nicotiana tabacum) BY-2 cell lines and in potato (Solanum tuberosum) plants. Key Results In BY-2 lines, over-expression of the three HyPRP genes with different types of N-terminal domains resulted in similar phenotypic changes, namely increased cell elongation, both in suspension culture and on solid media where the over-expression resulted in enhanced calli size. The over-expressing cells showed increased plasmolysis in a hypertonic mannitol solution and accelerated rate of protoplast release, suggesting loosening of the cell walls. In contrast to BY-2 lines, no phenotypic changes were observed in potato plants over-expressing the same or analogous HyPRP genes, presumably due to more complex compensatory mechanisms in planta. Conclusions Based on the results from BY-2 lines, we propose that HyPRPs, more specifically their C-terminal domains, represent a novel group of proteins involved in cell expansion. PMID:22028464

Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2.

PubMed

Tossavainen, Helena; Aitio, Olli; Hellman, Maarit; Saksela, Kalle; Permi, Perttu

2016-07-29

We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728-1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nm). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this affinity. Thus, via optimization of such dynamic electrostatic forces, viral peptides have evolved a superior binding affinity for amphiphysin-2 SH3 compared with typical cellular ligands, such as dynamin, thereby enabling hijacking of amphiphysin-2 SH3-regulated host cell processes by these viruses. Moreover, our data show that the previously described consensus sequence PXRPXR for amphiphysin SH3 ligands is inaccurate and instead define it as an extended Class II binding motif PXXPXRpXR, where additional positive charges between the two constant arginine residues can give rise to extraordinary high SH3 binding affinity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Phytocalpain controls the proliferation and differentiation fates of cells in plant organ development.

PubMed

Ahn, Joon-Woo; Kim, Moonil; Lim, Jeong Hwa; Kim, Gyung-Tae; Pai, Hyun-Sook

2004-06-01

Calpain, a calcium-dependent cysteine protease, plays an essential role in basic cellular processes in animal cells, including cell proliferation, apoptosis, and differentiation. NbDEK encodes the calpain homolog of N. benthamiana. In this study, virus-induced gene silencing (VIGS) of NbDEK resulted in arrested organ development and hyperplasia in all the major plant organs examined. The epidermal layers of the leaves and stems were covered with hyperproliferating cell masses, and stomata and trichome development was severely inhibited. During flower development, a single dome-like structure was grown from the flower meristem to generate a large cylinder-shaped flower lacking any floral organs. At the cellular level, cell division was sustained in tissues that were otherwise already differentiated, and cell differentiation was severely hampered. NbDEK is ubiquitously expressed in all the plant tissues examined. In the abnormal organs of the NbDEK VIGS lines, protein levels of D-type cyclins (CycD)2, CycD3, and proliferating cell nuclear antigen (PCNA) were greatly elevated, and transcription of E2F (E2 promoter binding factor), E2F-regulated genes, retinoblastoma (Rb), and KNOTTED1 (KN1)-type homeobox genes was also stimulated. These results suggest that phytocalpain is a key regulator of cell proliferation and differentiation during plant organogenesis, and that it acts partly by controlling the CycD/Rb pathway.

Contextual analysis of immunological response through whole-organ fluorescent imaging.

PubMed

Woodruff, Matthew C; Herndon, Caroline N; Heesters, B A; Carroll, Michael C

2013-09-01

As fluorescent microscopy has developed, significant insights have been gained into the establishment of immune response within secondary lymphoid organs, particularly in draining lymph nodes. While established techniques such as confocal imaging and intravital multi-photon microscopy have proven invaluable, they provide limited insight into the architectural and structural context in which these responses occur. To interrogate the role of the lymph node environment in immune response effectively, a new set of imaging tools taking into account broader architectural context must be implemented into emerging immunological questions. Using two different methods of whole-organ imaging, optical clearing and three-dimensional reconstruction of serially sectioned lymph nodes, fluorescent representations of whole lymph nodes can be acquired at cellular resolution. Using freely available post-processing tools, images of unlimited size and depth can be assembled into cohesive, contextual snapshots of immunological response. Through the implementation of robust iterative analysis techniques, these highly complex three-dimensional images can be objectified into sortable object data sets. These data can then be used to interrogate complex questions at the cellular level within the broader context of lymph node biology. By combining existing imaging technology with complex methods of sample preparation and capture, we have developed efficient systems for contextualizing immunological phenomena within lymphatic architecture. In combination with robust approaches to image analysis, these advances provide a path to integrating scientific understanding of basic lymphatic biology into the complex nature of immunological response.

Toxin–antitoxin systems

PubMed Central

Unterholzner, Simon J; Poppenberger, Brigitte; Rozhon, Wilfried

2013-01-01

Toxin–antitoxin (TA) systems are small genetic elements composed of a toxin gene and its cognate antitoxin. The toxins of all known TA systems are proteins while the antitoxins are either proteins or non-coding RNAs. Based on the molecular nature of the antitoxin and its mode of interaction with the toxin the TA modules are currently grouped into five classes. In general, the toxin is more stable than the antitoxin but the latter is expressed to a higher level. If supply of the antitoxin stops, for instance under special growth conditions or by plasmid loss in case of plasmid encoded TA systems, the antitoxin is rapidly degraded and can no longer counteract the toxin. Consequently, the toxin becomes activated and can act on its cellular targets. Typically, TA toxins act on crucial cellular processes including translation, replication, cytoskeleton formation, membrane integrity, and cell wall biosynthesis. TA systems and their components are also versatile tools for a multitude of purposes in basic research and biotechnology. Currently, TA systems are frequently used for selection in cloning and for single protein expression in living bacterial cells. Since several TA toxins exhibit activity in yeast and mammalian cells they may be useful for applications in eukaryotic systems. TA modules are also considered as promising targets for the development of antibacterial drugs and their potential to combat viral infection may aid in controlling infectious diseases. PMID:24251069

Nanotechnology Research: Applications in Nutritional Sciences12

PubMed Central

Srinivas, Pothur R.; Philbert, Martin; Vu, Tania Q.; Huang, Qingrong; Kokini, Josef L.; Saos, Etta; Chen, Hongda; Peterson, Charles M.; Friedl, Karl E.; McDade-Ngutter, Crystal; Hubbard, Van; Starke-Reed, Pamela; Miller, Nancy; Betz, Joseph M.; Dwyer, Johanna; Milner, John; Ross, Sharon A.

2010-01-01

The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of ∼1–100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled “Nanotechnology Research: Applications in Nutritional Sciences” was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities. PMID:19939997

Redox Regulation of Protein Kinases

PubMed Central

Truong, Thu H.; Carroll, Kate S.

2015-01-01

Protein kinases represent one of the largest families of genes found in eukaryotes. Kinases mediate distinct cellular processes ranging from proliferation, differentiation, survival, and apoptosis. Ligand-mediated activation of receptor kinases can lead to the production of endogenous H2O2 by membrane-bound NADPH oxidases. In turn, H2O2 can be utilized as a secondary messenger in signal transduction pathways. This review presents an overview of the molecular mechanisms involved in redox regulation of protein kinases and its effects on signaling cascades. In the first half, we will focus primarily on receptor tyrosine kinases (RTKs), whereas the latter will concentrate on downstream non-receptor kinases involved in relaying stimulant response. Select examples from the literature are used to highlight the functional role of H2O2 regarding kinase activity, as well as the components involved in H2O2 production and regulation during cellular signaling. In addition, studies demonstrating direct modulation of protein kinases by H2O2 through cysteine oxidation will be emphasized. Identification of these redox-sensitive residues may help uncover signaling mechanisms conserved within kinase subfamilies. In some cases, these residues can even be exploited as targets for the development of new therapeutics. Continued efforts in this field will further basic understanding of kinase redox regulation, and delineate the mechanisms involved in physiologic and pathological H2O2 responses. PMID:23639002

The Faceted Discrete Growth and Phase Differentiation During the Directional Solidification of 20SiMnMo5 Steel

NASA Astrophysics Data System (ADS)

Ma, Xiaoping; Li, Dianzhong

2018-07-01

The microstructures, segregation and cooling curve were investigated in the directional solidification of 20SiMnMo5 steel. The typical characteristic of faceted growth is identified. The microstructures within the single cellular and within the single dendritic arm, together with the contradictive segregation distribution against the cooling curve, verify the discrete crystal growth in multi-scales. Not only the single cellular/dendritic arm but also the single martensite zone within the single cellular/dendritic arm is produced by the discrete growth. In the viewpoint of segregation, the basic domain following continuous growth has not been revealed. Along with the multi-scale faceted discrete growth, the phase differentiation happens for both the solid and liquid. The differentiated liquid phases appear and evolve with different sizes, positions, compositions and durations. The physical mechanism for the faceted discrete growth is qualitatively established based on the nucleation of new faceted steps induced by the composition gradient and temperature gradient.

The Faceted Discrete Growth and Phase Differentiation During the Directional Solidification of 20SiMnMo5 Steel

NASA Astrophysics Data System (ADS)

Ma, Xiaoping; Li, Dianzhong

2018-03-01

The microstructures, segregation and cooling curve were investigated in the directional solidification of 20SiMnMo5 steel. The typical characteristic of faceted growth is identified. The microstructures within the single cellular and within the single dendritic arm, together with the contradictive segregation distribution against the cooling curve, verify the discrete crystal growth in multi-scales. Not only the single cellular/dendritic arm but also the single martensite zone within the single cellular/dendritic arm is produced by the discrete growth. In the viewpoint of segregation, the basic domain following continuous growth has not been revealed. Along with the multi-scale faceted discrete growth, the phase differentiation happens for both the solid and liquid. The differentiated liquid phases appear and evolve with different sizes, positions, compositions and durations. The physical mechanism for the faceted discrete growth is qualitatively established based on the nucleation of new faceted steps induced by the composition gradient and temperature gradient.

Are microRNAs true sensors of ageing and cellular senescence?

PubMed

Williams, Justin; Smith, Flint; Kumar, Subodh; Vijayan, Murali; Reddy, P Hemachandra

2017-05-01

All living beings are programmed to death due to aging and age-related processes. Aging is a normal process of every living species. While all cells are inevitably progressing towards death, many disease processes accelerate the aging process, leading to senescence. Pathologies such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, cardiovascular disease, cancer, and skin diseases have been associated with deregulated aging. Healthy aging can delay onset of all age-related diseases. Genetics and epigenetics are reported to play large roles in accelerating and/or delaying the onset of age-related diseases. Cellular mechanisms of aging and age-related diseases are not completely understood. However, recent molecular biology discoveries have revealed that microRNAs (miRNAs) are potential sensors of aging and cellular senescence. Due to miRNAs capability to bind to the 3' untranslated region (UTR) of mRNA of specific genes, miRNAs can prevent the translation of specific genes. The purpose of our article is to highlight recent advancements in miRNAs and their involvement in cellular changes in aging and senescence. Our article discusses the current understanding of cellular senescence, its interplay with miRNAs regulation, and how they both contribute to disease processes. Copyright © 2016 Elsevier B.V. All rights reserved.

Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

PubMed

Kim, Tae-il; McCall, Jordan G; Jung, Yei Hwan; Huang, Xian; Siuda, Edward R; Li, Yuhang; Song, Jizhou; Song, Young Min; Pao, Hsuan An; Kim, Rak-Hwan; Lu, Chaofeng; Lee, Sung Dan; Song, Il-Sun; Shin, Gunchul; Al-Hasani, Ream; Kim, Stanley; Tan, Meng Peun; Huang, Yonggang; Omenetto, Fiorenzo G; Rogers, John A; Bruchas, Michael R

2013-04-12

Successful integration of advanced semiconductor devices with biological systems will accelerate basic scientific discoveries and their translation into clinical technologies. In neuroscience generally, and in optogenetics in particular, the ability to insert light sources, detectors, sensors, and other components into precise locations of the deep brain yields versatile and important capabilities. Here, we introduce an injectable class of cellular-scale optoelectronics that offers such features, with examples of unmatched operational modes in optogenetics, including completely wireless and programmed complex behavioral control over freely moving animals. The ability of these ultrathin, mechanically compliant, biocompatible devices to afford minimally invasive operation in the soft tissues of the mammalian brain foreshadow applications in other organ systems, with potential for broad utility in biomedical science and engineering.

The regulation of autophagy differentially affects Trypanosoma cruzi metacyclogenesis.

PubMed

Vanrell, María Cristina; Losinno, Antonella Denisse; Cueto, Juan Agustín; Balcazar, Darío; Fraccaroli, Laura Virginia; Carrillo, Carolina; Romano, Patricia Silvia

2017-11-01

Autophagy is a cellular process required for the removal of aged organelles and cytosolic components through lysosomal degradation. All types of eukaryotic cells from yeasts to mammalian cells have the machinery to activate autophagy as a result of many physiological and pathological situations. The most frequent stimulus of autophagy is starvation and the result, in this case, is the fast generation of utilizable food (e.g. amino acids and basic nutrients) to maintain the vital biological processes. In some organisms, starvation also triggers other associated processes such as differentiation. The protozoan parasite Trypanosoma cruzi undergoes a series of differentiation processes throughout its complex life cycle. Although not all autophagic genes have been identified in the T. cruzi genome, previous works have demonstrated the presence of essential autophagic-related proteins. Under starvation conditions, TcAtg8, which is the parasite homolog of Atg8/LC3 in other organisms, is located in autophagosome-like vesicles. In this work, we have characterized the autophagic pathway during T. cruzi differentiation from the epimastigote to metacyclic trypomastigote form, a process called metacyclogenesis. We demonstrated that autophagy is stimulated during metacyclogenesis and that the induction of autophagy promotes this process. Moreover, with exception of bafilomycin, other classical autophagy modulators have similar effects on T. cruzi autophagy. We also showed that spermidine and related polyamines can positively regulate parasite autophagy and differentiation. We concluded that both polyamine metabolism and autophagy are key processes during T. cruzi metacyclogenesis that could be exploited as drug targets to avoid the parasite cycle progression.

Understanding the cancer cell phenotype beyond the limitations of current omics analyses.

PubMed

Moreno-Sánchez, Rafael; Saavedra, Emma; Gallardo-Pérez, Juan Carlos; Rumjanek, Franklin D; Rodríguez-Enríquez, Sara

2016-01-01

Efforts to understand the mechanistic principles driving cancer metabolism and proliferation have been lately governed by genomic, transcriptomic and proteomic studies. This paper analyzes the caveats of these approaches. As molecular biology's central dogma proposes a unidirectional flux of information from genes to mRNA to proteins, it has frequently been assumed that monitoring the changes in the gene sequences and in mRNA and protein contents is sufficient to explain complex cellular processes. Such a stance commonly disregards that post-translational modifications can alter the protein function/activity and also that regulatory mechanisms enter into action, to coordinate the protein activities of pathways/cellular processes, in order to keep the cellular homeostasis. Hence, the actual protein activities (as enzymes/transporters/receptors) and their regulatory mechanisms ultimately dictate the final outcomes of a pathway/cellular process. In this regard, it is here documented that the mRNA levels of many metabolic enzymes and transcriptional factors have no correlation with the respective protein contents and activities. The validity of current clinical mRNA-based tests and proposed metabolite biomarkers for cancer detection/prognosis is also discussed. Therefore, it is proposed that, to achieve a thorough understanding of the modifications undergone by proliferating cancer cells, it is mandatory to experimentally analyze the cellular processes at the functional level. This could be achieved (a) locally, by examining the actual protein activities in the cell and their kinetic properties (or at least kinetically characterize the most controlling steps of the pathway/cellular process); (b) systemically, by analyzing the main fluxes of the pathway/cellular process, and how they are modulated by metabolites, all which should contribute to comprehending the regulatory mechanisms that have been altered in cancer cells. By adopting a more holistic approach it may become possible to improve the design of therapeutic strategies that would target cancer cells more specifically. © 2015 FEBS.

Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepuberal mouse testes.

PubMed

Isoler-Alcaraz, J; Fernández-Pérez, D; Larriba, E; Del Mazo, J

2017-10-18

Recently, an effective testis culture method using a gas-liquid interphase, capable of differentiate male germ cells from neonatal spermatogonia to spermatozoa has been developed. Nevertheless, this methodology needs deep analyses that allow future experimental approaches in basic, pathologic and/or reprotoxicologic studies. Because of this, we characterized at cellular and molecular levels the entire in vitro spermatogenic progression, in order to understand and evaluate the characteristics that define the spermatogenic process in ex vivo cultured testes compared to the in vivo development. Testicular explants of CD1 mice aged 6 and 10 days post-partum were respectively cultured during 55 and 89 days. Cytological and molecular approaches were performed, analyzing germ cell proportion at different time culture points, meiotic markers immunodetecting synaptonemal complex protein SYCP3 by immunocytochemistry and the relative expression of different marker genes along the differentiation process by Reverse Transcription - quantitative Polymerase Chain Reaction. In addition, microRNA and piwi-interactingRNA profiles were also evaluated by Next Generation Sequencing and bioinformatic approaches. The method promoted and maintained the spermatogenic process during 89 days. At a cytological level we detected spermatogenic development delays of cultured explants compared to the natural in vivo process. The expression of different spermatogenic stages gene markers correlated with the proportion of different cell types detected in the cytological preparations. In vitro progression analysis of the different spermatogenic cell types, from both 6.5 dpp and 10.5 dpp testes explants, has revealed a relative delay in relation to in vivo process. The expression of the genes studied as biomarkers correlates with the cytologically and functional detected progression and differential expression identified in vivo. After a first analysis of deep sequencing data it has been observed that as long as cultures progress, the proportion of microRNAs declined respect to piwi-interactingRNAs levels that increased, showing a similar propensity than which happens in in vivo spermatogenesis. Our study allows to improve and potentially to control the ex vivo spermatogenesis development, opening new perspectives in the reproductive biology fields including male fertility.

Targeting PCNA Phosphorylation in Breast Cancer

DTIC Science & Technology

2012-04-01

inhibitor and dyes. These basic peptides and polycationic peptoids were labeled with fluorescein and used to assess the effect of structure on cellular... substitution of a peptoid conjugate that was synthesized during the project period. Additional types of analogs were prepared as well each providing...Broceta, A., Diezmann, F., Ou-Yang, C. Y., Fara, M. A. & Bradley, M. Synthesis, penetrability and intracellular targeting of fluorescein -tagged

The Second Annual Symposium of the NASA Specialized Center of Research and Training (NSCORT) in Gravitational Biology.

PubMed

Spooner, B S

1993-04-01

The second annual meeting of the NSCORT in Gravitational Biology was held at Kansas State University on September 29-October 1, 1992. Symposium presentations at the meeting included ones on basic gravitational cellular and developmental biology, spaceflight hardware for biological studies, studies on Space Shuttle, and special talks on Space Station Freedom and on life support systems.

Mechanisms and disease relevance of neutrophil extracellular trap formation.

PubMed

Van Avondt, Kristof; Hartl, Dominik

2018-03-15

While the microscopic appearance of neutrophil extracellular traps (NETs) has fascinated basic researchers since its discovery, the (patho)physiological mechanisms triggering NET release, the disease relevance and clinical translatability of this unconventional cellular mechanism remained poorly understood. Here, we summarize and discuss current concepts of the mechanisms and disease relevance of NET formation. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

[What it means to be "infected"--how a human body, or health professionals combat "infection"].

PubMed

Arakawa, Soichi

2011-09-01

Human immunology and relationship between immune mechanism and infection were explained. Humoral immunity and cellular immunity collaborate properly and eliminate microorganisms. In immunocompromised host these mechanisms are broken. For prevention of healthcare associated infections, standard precausion is important basically. Additionary, according to the status of the patient, contact precaution, droplet precaution or airborne precaution should be applied.

Multifunctional Thermal Structures Using Cellular Contact-Aided Complaint Mechanisms

DTIC Science & Technology

2016-10-31

control . During this research effort, designs of increasing sophistication consistently outstripped the ability to fabricate them. Basic questions...using   non -­dimensional  models   In continuing design research , a topology optimization approach was crafted to maximize the thermal performance of the...methods could conceivably produce the elegant but complex material and geometric designs contemplated. Continued research is needed to improve the

Multifunctional Thermal Structures Using Cellular Contract-Aided Complaint Mechanisms

DTIC Science & Technology

2017-01-26

control . During this research effort, designs of increasing sophistication consistently outstripped the ability to fabricate them. Basic questions...using   non -­dimensional  models   In continuing design research , a topology optimization approach was crafted to maximize the thermal performance of the...methods could conceivably produce the elegant but complex material and geometric designs contemplated. Continued research is needed to improve the

The Second Annual Symposium of the NASA Specialized Center of Research and Training (NSCORT) in Gravitational Biology

NASA Technical Reports Server (NTRS)

Spooner, B. S.

1993-01-01

The second annual meeting of the NSCORT in Gravitational Biology was held at Kansas State University on September 29-October 1, 1992. Symposium presentations at the meeting included ones on basic gravitational cellular and developmental biology, spaceflight hardware for biological studies, studies on Space Shuttle, and special talks on Space Station Freedom and on life support systems.

Emergence of tissue mechanics from cellular processes: shaping a fly wing

NASA Astrophysics Data System (ADS)

Merkel, Matthias; Etournay, Raphael; Popovic, Marko; Nandi, Amitabha; Brandl, Holger; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

Nowadays, biologistsare able to image biological tissueswith up to 10,000 cells in vivowhere the behavior of each individual cell can be followed in detail.However, how precisely large-scale tissue deformation and stresses emerge from cellular behavior remains elusive. Here, we study this question in the developing wing of the fruit fly. To this end, we first establish a geometrical framework that exactly decomposes tissue deformation into contributions by different kinds of cellular processes. These processes comprise cell shape changes, cell neighbor exchanges, cell divisions, and cell extrusions. As the key idea, we introduce a tiling of the cellular network into triangles. This approach also reveals that tissue deformation can also be created by correlated cellular motion. Based on quantifications using these concepts, we developed a novel continuum mechanical model for the fly wing. In particular, our model includes active anisotropic stresses and a delay in the response of cell rearrangements to material stresses. A different approach to study the emergence of tissue mechanics from cellular behavior are cell-based models. We characterize the properties of a cell-based model for 3D tissues that is a hybrid between single particle models and the so-called vertex models.

Detecting the Extent of Cellular Decomposition after Sub-Eutectoid Annealing in Rolled UMo Foils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kautz, Elizabeth J.; Jana, Saumyadeep; Devaraj, Arun

2017-07-31

This report presents an automated image processing approach to quantifying microstructure image data, specifically the extent of eutectoid (cellular) decomposition in rolled U-10Mo foils. An image processing approach is used here to be able to quantitatively describe microstructure image data in order to relate microstructure to processing parameters (time, temperature, deformation).

Protein arginine methylation: Cellular functions and methods of analysis.

PubMed

Pahlich, Steffen; Zakaryan, Rouzanna P; Gehring, Heinz

2006-12-01

During the last few years, new members of the growing family of protein arginine methyltransferases (PRMTs) have been identified and the role of arginine methylation in manifold cellular processes like signaling, RNA processing, transcription, and subcellular transport has been extensively investigated. In this review, we describe recent methods and findings that have yielded new insights into the cellular functions of arginine-methylated proteins, and we evaluate the currently used procedures for the detection and analysis of arginine methylation.

Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis.

PubMed

Heier, Eva-Carina; Meier, Anna; Julich-Haertel, Henrike; Djudjaj, Sonja; Rau, Monica; Tschernig, Thomas; Geier, Andreas; Boor, Peter; Lammert, Frank; Lukacs-Kornek, Veronika

2017-06-01

Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The identification of molecular and cellular factors that determine the progression of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic cells (DCs) represent a heterogeneous cell population among which CD103 + DCs play a significant role in immunity and tolerance. We aimed to clarify the role of this DC subset in the pathomechanism of NASH. Steatosis progression towards steatohepatitis was analysed using multicolor FACS analyses, cytokine and qPCR array in high sucrose diet (HSD) and methionine and choline deficient diet (MCD) fed wild-type and basic leucine zipper transcription factor, ATF-Like-3 (Batf3) deficient animals, which lack CD103 + DCs (classical type-1 DC, cDC1s). Metabolic challenge of Batf3 -/- animals resulted in the progression of steatosis towards steatohepatitis, manifesting by an increased influx of inflammatory cells into the liver and elevated inflammatory cytokine production of myeloid cells upon innate stimuli. However, the lack of cDC1s did not affect cellular apoptosis and fibrosis progression but altered genes involved in lipid metabolism. The adoptive transfer of CD103 + cDC1s to Batf3 deficient animals reversed these observed changes and more importantly could attenuate cellular damage and inflammation in established murine steatohepatitis. Here, we have identified the murine CD103 + cDC1s as a protective DC subtype that influences the pro-anti-inflammatory balance and protects the liver from metabolic damage. As guardians of liver integrity, they play a key role in the inflammatory process during the development of steatohepatitis in mice. Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can lead to non-alcoholic steatohepatitis (NASH). The current study demonstrated that a specific murine dendritic cell subtype possesses a potent regulatory role to influence the inflammatory milieu of the liver in this process. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Genetic Dominance & Cellular Processes

ERIC Educational Resources Information Center

Seager, Robert D.

2014-01-01

In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

ERIC Educational Resources Information Center

Brown, Mary H.; Schwartz, Renee S.

2009-01-01

The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

The metabolite profiling of coastal coccolithophorid species Pleurochrysis carterae (Haptophyta)

NASA Astrophysics Data System (ADS)

Zhou, Chengxu; Luo, Jie; Ye, Yangfang; Yan, Xiaojun; Liu, Baoning; Wen, Xin

2016-07-01

Pleurochrysis carterae is a calcified coccolithophorid species that usually blooms in the coastal area and causes aquaculture losses. The cellular calcification, blooming and many other critical species specific eco-physiological processes are closely related to various metabolic pathways. The purpose of this study is to apply the unbiased and non-destructive method of nuclear magnetic resonance (NMR) to detect the unknown holistic metabolite of P. carterae. The results show that NMR spectroscopic method is practical in the analysis of metabolites of phytoplankton. The metabolome of P. carterae was dominated by 26 metabolites involved in a number of different primary and secondary metabolic pathways. Organic acids and their derivatives, amino acids, sugars, nucleic aides were mainly detected. The abundant metabolites are that closely related to the process of cellular osmotic adjustment, which possibly reflect the active ability of P. carterae to adapt to the versatile coastal niche. DMSP (dimethylsulphoniopropionate) was the most dominant metabolite in P. carterae, up to 2.065±0.278 mg/g lyophilized cells, followed by glutamate and lactose, the contents were 0.349±0.035 and 0.301±0.073 mg/g lyophilized cells respectively. Other metabolites that had the content ranged between 0.1-0.2 mg/g lyophilized cells were alanine, isethionate and arabinose. Amino acid (valine, phenylalanine, isoleucine, tyrosine), organic acid salts (lactate, succinate), scyllitol and uracil had content ranged from 0.01 to below 0.1 mg/g lyophilized cells. Trigonelline, fumarate and formate were detected in very low content (only thousandths of 1 mg per gram of lyophilized cells or below). Our results of the holistic metabolites of P. carterae are the basic references for the further studies when multiple problems will be addressed to this notorious blooming calcifying species.

Computational study of noise in a large signal transduction network.

PubMed

Intosalmi, Jukka; Manninen, Tiina; Ruohonen, Keijo; Linne, Marja-Leena

2011-06-21

Biochemical systems are inherently noisy due to the discrete reaction events that occur in a random manner. Although noise is often perceived as a disturbing factor, the system might actually benefit from it. In order to understand the role of noise better, its quality must be studied in a quantitative manner. Computational analysis and modeling play an essential role in this demanding endeavor. We implemented a large nonlinear signal transduction network combining protein kinase C, mitogen-activated protein kinase, phospholipase A2, and β isoform of phospholipase C networks. We simulated the network in 300 different cellular volumes using the exact Gillespie stochastic simulation algorithm and analyzed the results in both the time and frequency domain. In order to perform simulations in a reasonable time, we used modern parallel computing techniques. The analysis revealed that time and frequency domain characteristics depend on the system volume. The simulation results also indicated that there are several kinds of noise processes in the network, all of them representing different kinds of low-frequency fluctuations. In the simulations, the power of noise decreased on all frequencies when the system volume was increased. We concluded that basic frequency domain techniques can be applied to the analysis of simulation results produced by the Gillespie stochastic simulation algorithm. This approach is suited not only to the study of fluctuations but also to the study of pure noise processes. Noise seems to have an important role in biochemical systems and its properties can be numerically studied by simulating the reacting system in different cellular volumes. Parallel computing techniques make it possible to run massive simulations in hundreds of volumes and, as a result, accurate statistics can be obtained from computational studies. © 2011 Intosalmi et al; licensee BioMed Central Ltd.

A genome-wide analysis of biomineralization-related proteins in the sea urchin Strongylocentrotus purpuratus.

PubMed

Livingston, B T; Killian, C E; Wilt, F; Cameron, A; Landrum, M J; Ermolaeva, O; Sapojnikov, V; Maglott, D R; Buchanan, A M; Ettensohn, C A

2006-12-01

Biomineralization, the biologically controlled formation of mineral deposits, is of widespread importance in biology, medicine, and engineering. Mineralized structures are found in most metazoan phyla and often have supportive, protective, or feeding functions. Among deuterostomes, only echinoderms and vertebrates produce extensive biomineralized structures. Although skeletons appeared independently in these two groups, ancestors of the vertebrates and echinoderms may have utilized similar components of a shared genetic "toolkit" to carry out biomineralization. The present study had two goals. First, we sought to expand our understanding of the proteins involved in biomineralization in the sea urchin, a powerful model system for analyzing the basic cellular and molecular mechanisms that underlie this process. Second, we sought to shed light on the possible evolutionary relationships between biomineralization in echinoderms and vertebrates. We used several computational methods to survey the genome of the purple sea urchin Strongylocentrotus purpuratus for gene products involved in biomineralization. Our analysis has greatly expanded the collection of biomineralization-related proteins. We have found that these proteins are often members of small families encoded by genes that are clustered in the genome. Most of the proteins are sea urchin-specific; that is, they have no apparent homologues in other invertebrate deuterostomes or vertebrates. Similarly, many of the vertebrate proteins that mediate mineral deposition do not have counterparts in the S. purpuratus genome. Our findings therefore reveal substantial differences in the primary sequences of proteins that mediate biomineral formation in echinoderms and vertebrates, possibly reflecting loose constraints on the primary structures of the proteins involved. On the other hand, certain cellular and molecular processes associated with earlier events in skeletogenesis appear similar in echinoderms and vertebrates, leaving open the possibility of deeper evolutionary relationships.

Enhancing the cellular uptake of siRNA duplexes following noncovalent packaging with protein transduction domain peptides.

PubMed

Meade, Bryan R; Dowdy, Steven F

2008-03-01

The major limitation in utilizing information rich macromolecules for basic science and therapeutic applications is the inability of these large molecules to readily diffuse across the cellular membrane. While this restriction represents an efficient defense system against cellular penetration of unwanted foreign molecules and thus a crucial component of cell survival, overcoming this cellular characteristic for the intracellular delivery of macromolecules has been the focus of a large number of research groups worldwide. Recently, with the discovery of RNA interference, many of these groups have redirected their attention and have applied previously characterized cell delivery methodologies to synthetic short interfering RNA duplexes (siRNA). Protein transduction domain and cell penetrating peptides have been shown to enhance the delivery of multiple types of macromolecular cargo including peptides, proteins and antisense oligonucleotides and are now being utilized to enhance the cellular uptake of siRNA molecules. The dense cationic charge of these peptides that is critical for interaction with cell membrane components prior to internalization has also been shown to readily package siRNA molecules into stable nanoparticles that are capable of traversing the cell membrane. This review discusses the recent advances in noncovalent packaging of siRNA molecules with cationic peptides and the potential for the resulting complexes to successfully induce RNA interference within both in vitro and in vivo settings.

Four domains: The fundamental unicell and Post-Darwinian Cognition-Based Evolution.

PubMed

Miller, William B; Torday, John S

2018-04-13

Contemporary research supports the viewpoint that self-referential cognition is the proper definition of life. From that initiating platform, a cohesive alternative evolutionary narrative distinct from standard Neodarwinism can be presented. Cognition-Based Evolution contends that biological variation is a product of a self-reinforcing information cycle that derives from self-referential attachment to biological information space-time with its attendant ambiguities. That information cycle is embodied through obligatory linkages among energy, biological information, and communication. Successive reiterations of the information cycle enact the informational architectures of the basic unicellular forms. From that base, inter-domain and cell-cell communications enable genetic and cellular variations through self-referential natural informational engineering and cellular niche construction. Holobionts are the exclusive endpoints of that self-referential cellular engineering as obligatory multicellular combinations of the essential Four Domains: Prokaryota, Archaea, Eukaryota and the Virome. Therefore, it is advocated that these Four Domains represent the perpetual object of the living circumstance rather than the visible macroorganic forms. In consequence, biology and its evolutionary development can be appraised as the continual defense of instantiated cellular self-reference. As the survival of cells is as dependent upon limitations and boundaries as upon any freedom of action, it is proposed that selection represents only one of many forms of cellular constraint that sustain self-referential integrity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantitative phase-digital holographic microscopy: a new imaging modality to identify original cellular biomarkers of diseases

NASA Astrophysics Data System (ADS)

Marquet, P.; Rothenfusser, K.; Rappaz, B.; Depeursinge, C.; Jourdain, P.; Magistretti, P. J.

2016-03-01

Quantitative phase microscopy (QPM) has recently emerged as a powerful label-free technique in the field of living cell imaging allowing to non-invasively measure with a nanometric axial sensitivity cell structure and dynamics. Since the phase retardation of a light wave when transmitted through the observed cells, namely the quantitative phase signal (QPS), is sensitive to both cellular thickness and intracellular refractive index related to the cellular content, its accurate analysis allows to derive various cell parameters and monitor specific cell processes, which are very likely to identify new cell biomarkers. Specifically, quantitative phase-digital holographic microscopy (QP-DHM), thanks to its numerical flexibility facilitating parallelization and automation processes, represents an appealing imaging modality to both identify original cellular biomarkers of diseases as well to explore the underlying pathophysiological processes.

Fluorescence microscopy: A tool to study autophagy

NASA Astrophysics Data System (ADS)

Rai, Shashank; Manjithaya, Ravi

2015-08-01

Autophagy is a cellular recycling process through which a cell degrades old and damaged cellular components such as organelles and proteins and the degradation products are reused to provide energy and building blocks. Dysfunctional autophagy is reported in several pathological situations. Hence, autophagy plays an important role in both cellular homeostasis and diseased conditions. Autophagy can be studied through various techniques including fluorescence based microscopy. With the advancements of newer technologies in fluorescence microscopy, several novel processes of autophagy have been discovered which makes it an essential tool for autophagy research. Moreover, ability to tag fluorescent proteins with sub cellular targets has enabled us to evaluate autophagy processes in real time under fluorescent microscope. In this article, we demonstrate different aspects of autophagy in two different model organisms i.e. yeast and mammalian cells, with the help of fluorescence microscopy.

Petrographic, geochemical and isotopic evidence of crustal assimilation processes in the Ponte Nova alkaline mafic-ultramafic massif, SE Brazil

NASA Astrophysics Data System (ADS)

Azzone, Rogério Guitarrari; Montecinos Munoz, Patricio; Enrich, Gaston Eduardo Rojas; Alves, Adriana; Ruberti, Excelso; Gomes, Celsode Barros

2016-09-01

Crustal assimilation plus crystal fractionation processes of different basanite magma batches control the evolution of the Ponte Nova cretaceous alkaline mafic-ultramafic massif in SE Brazil. This massif is composed of several intrusions, the main ones with a cumulate character. Disequilibrium features in the early-crystallized phases (e.g., corrosion and sieve textures in cores of clinopyroxene crystals, spongy-cellular-textured plagioclase crystals, gulf corrosion texture in olivine crystals) and classical hybridization textures (e.g., blade biotite and acicular apatite crystals) provide strong evidence of open-system behavior. All samples are olivine- and nepheline-normative rocks with basic-ultrabasic and potassic characters and variable incompatible element enrichments. The wide ranges of whole-rock 87Sr/86Sri and 143Nd/144Ndi ratios (0.70432-0.70641 and 0.512216-0.512555, respectively) are indicative of crustal contribution from the Precambrian basement host rocks. Plagioclase and apatite 87Sr/86Sr ratios (0.70422-0.70927) obtained for the most primitive samples of each intrusion indicate disequilibrium conditions from early- to principal-crystallization stages. Isotope mixing-model curves between the least contaminated alkaline basic magma and heterogeneous local crustal components indicate that each intrusion of the massif is differentiated from the others by varied degrees of crustal contribution. The primary mechanisms of crustal contribution to the Ponte Nova massif involve the assimilation of host rock xenoliths during the development of the chamber environment and the assimilation of partial melts from the surrounding host rocks. Thermodynamic models using the melts algorithm indicate that parental alkaline basic magmas can be strongly affected by contamination processes subsequently to their initial stages of crystallization when there is sufficient energy to assimilate partial melts of crustal host rocks. The assimilation processes are considered to be responsible for the increse in the K2O/Na2O, Ba/Sr and Rb/Sr ratios. This enrichment was associated with the relevant role of biotite breakdown in the assimilated host rock partial melts. The petrological model for the Ponte Nova massif is explained as repeated influxes of antecryst-laden basanite magmas that deposited most of their suspended crystals on the floor of the upper-crust magma chamber. Each intrusion is representative of relatively primitive olivine- and clinopyroxene-phyric basanites that had assimilated different degrees of partial melts of heterogeneous host rocks. This study reveals the relevant role of crustal assimilation processes in the magmatic evolution of nepheline-normative rocks, especially in upper-crust chamber environments.

Cellular water distribution, transport, and its investigation methods for plant-based food material.

PubMed

Khan, Md Imran H; Karim, M A

2017-09-01

Heterogeneous and hygroscopic characteristics of plant-based food material make it complex in structure, and therefore water distribution in its different cellular environments is very complex. There are three different cellular environments, namely the intercellular environment, the intracellular environment, and the cell wall environment inside the food structure. According to the bonding strength, intracellular water is defined as loosely bound water, cell wall water is categorized as strongly bound water, and intercellular water is known as free water (FW). During food drying, optimization of the heat and mass transfer process is crucial for the energy efficiency of the process and the quality of the product. For optimizing heat and mass transfer during food processing, understanding these three types of waters (strongly bound, loosely bound, and free water) in plant-based food material is essential. However, there are few studies that investigate cellular level water distribution and transport. As there is no direct method for determining the cellular level water distributions, various indirect methods have been applied to investigate the cellular level water distribution, and there is, as yet, no consensus on the appropriate method for measuring cellular level water in plant-based food material. Therefore, the main aim of this paper is to present a comprehensive review on the available methods to investigate the cellular level water, the characteristics of water at different cellular levels and its transport mechanism during drying. The effect of bound water transport on quality of food product is also discussed. This review article presents a comparative study of different methods that can be applied to investigate cellular water such as nuclear magnetic resonance (NMR), bioelectric impedance analysis (BIA), differential scanning calorimetry (DSC), and dilatometry. The article closes with a discussion of current challenges to investigating cellular water. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration of Proteomic, Transcriptional, and Interactome Data Reveals Hidden Signaling Components

PubMed Central

Huang, Shao-shan Carol; Fraenkel, Ernest

2009-01-01

Cellular signaling and regulatory networks underlie fundamental biological processes such as growth, differentiation, and response to the environment. Although there are now various high-throughput methods for studying these processes, knowledge of them remains fragmentary. Typically, the vast majority of hits identified by transcriptional, proteomic, and genetic assays lie outside of the expected pathways. These unexpected components of the cellular response are often the most interesting, because they can provide new insights into biological processes and potentially reveal new therapeutic approaches. However, they are also the most difficult to interpret. We present a technique, based on the Steiner tree problem, that uses previously reported protein-protein and protein-DNA interactions to determine how these hits are organized into functionally coherent pathways, revealing many components of the cellular response that are not readily apparent in the original data. Applied simultaneously to phosphoproteomic and transcriptional data for the yeast pheromone response, it identifies changes in diverse cellular processes that extend far beyond the expected pathways. PMID:19638617

The cellular transducer in bone: What is it?

PubMed

Taylor, David; Hazenberg, Jan; Lee, T Clive

2006-01-01

Bone is able to detect its strain environment and respond accordingly. In particular it is able to adapt to over-use and under-use by bone deposition or resorption. How can bone sense strain? Various physical mechanisms have been proposed for the so-called cellular transducer, but there is no conclusive proof for any one of them. This paper examines the theories and evidence, with particular reference to a new theory proposed by the authors, involving damage to cellular processes by microcracks. Experiments on bone samples ex-vivo showed that cracks cannot fracture osteocytes, but that cellular processes which span the crack can be broken. A theoretical model was developed for predicting the number of broken processes as a function of crack size and applied stress. This showed that signals emitted by fractured processes could be used to detect cracks which needed repairing and to provide information on the overall level of damage which could be used to initiate repair and adaptation responses.

Cellular Imaging With MRI.

PubMed

Makela, Ashley V; Murrell, Donna H; Parkins, Katie M; Kara, Jenna; Gaudet, Jeffrey M; Foster, Paula J

2016-10-01

Cellular magnetic resonance imaging (MRI) is an evolving field of imaging with strong translational and research potential. The ability to detect, track, and quantify cells in vivo and over time allows for studying cellular events related to disease processes and may be used as a biomarker for decisions about treatments and for monitoring responses to treatments. In this review, we discuss methods for labeling cells, various applications for cellular MRI, the existing limitations, strategies to address these shortcomings, and clinical cellular MRI.

Nanobodies and recombinant binders in cell biology

PubMed Central

Helma, Jonas; Cardoso, M. Cristina; Muyldermans, Serge

2015-01-01

Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. PMID:26056137

Solar Process Heat Basics | NREL

Science.gov Websites

Process Heat Basics Solar Process Heat Basics Commercial and industrial buildings may use the same , black metal panel mounted on a south-facing wall to absorb the sun's heat. Air passes through the many nonresidential buildings. A typical system includes solar collectors that work along with a pump, heat exchanger

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

PubMed

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

3D Printing Variable Stiffness Foams Using Viscous Thread Instability

NASA Astrophysics Data System (ADS)

Lipton, Jeffrey I.; Lipson, Hod

2016-08-01

Additive manufacturing of cellular structures has numerous applications ranging from fabrication of biological scaffolds and medical implants, to mechanical weight reduction and control over mechanical properties. Various additive manufacturing processes have been used to produce open regular cellular structures limited only by the resolution of the printer. These efforts have focused on printing explicitly designed cells or explicitly planning offsets between strands. Here we describe a technique for producing cellular structures implicitly by inducing viscous thread instability when extruding material. This process allows us to produce complex cellular structures at a scale that is finer than the native resolution of the printer. We demonstrate tunable effective elastic modulus and density that span two orders of magnitude. Fine grained cellular structures allow for fabrication of foams for use in a wide range of fields ranging from bioengineering, to robotics to food printing.

Chronic alcoholism: insights from neurophysiology.

PubMed

Campanella, S; Petit, G; Maurage, P; Kornreich, C; Verbanck, P; Noël, X

2009-01-01

Increasing knowledge of the anatomical structures and cellular processes underlying psychiatric disorders may help bridge the gap between clinical signs and basic physiological processes. Accordingly, considerable insight has been gained in recent years into a common psychiatric condition, i.e., chronic alcoholism. We reviewed various physiological parameters that are altered in chronic alcoholic patients compared to healthy individuals--continuous electroencephalogram, oculomotor measures, cognitive event-related potentials and event-related oscillations--to identify links between these physiological parameters, altered cognitive processes and specific clinical symptoms. Alcoholic patients display: (1) high beta and theta power in the resting electroencephalogram, suggesting hyperarousal of their central nervous system; (2) abnormalities in smooth pursuit eye movements, in saccadic inhibition during antisaccade tasks, and in prepulse inhibition, suggesting disturbed attention modulation and abnormal patterns of prefrontal activation that may stem from the same prefrontal "inhibitory" cortical dysfunction; (3) decreased amplitude for cognitive event-related potentials situated along the continuum of information-processing, suggesting that alcoholism is associated with neurophysiological deficits at the level of the sensory cortex and not only disturbances involving associative cortices and limbic structures; and (4) decreased theta, gamma and delta oscillations, suggesting cognitive disinhibition at a functional level. The heterogeneity of alcoholic disorders in terms of symptomatology, course and outcome is the result of various pathophysiological processes that physiological parameters may help to define. These alterations may be related to precise cognitive processes that could be easily monitored neurophysiologically in order to create more homogeneous subgroups of alcoholic individuals.

Modeling cell adhesion and proliferation: a cellular-automata based approach.

PubMed

Vivas, J; Garzón-Alvarado, D; Cerrolaza, M

Cell adhesion is a process that involves the interaction between the cell membrane and another surface, either a cell or a substrate. Unlike experimental tests, computer models can simulate processes and study the result of experiments in a shorter time and lower costs. One of the tools used to simulate biological processes is the cellular automata, which is a dynamic system that is discrete both in space and time. This work describes a computer model based on cellular automata for the adhesion process and cell proliferation to predict the behavior of a cell population in suspension and adhered to a substrate. The values of the simulated system were obtained through experimental tests on fibroblast monolayer cultures. The results allow us to estimate the cells settling time in culture as well as the adhesion and proliferation time. The change in the cells morphology as the adhesion over the contact surface progress was also observed. The formation of the initial link between cell and the substrate of the adhesion was observed after 100 min where the cell on the substrate retains its spherical morphology during the simulation. The cellular automata model developed is, however, a simplified representation of the steps in the adhesion process and the subsequent proliferation. A combined framework of experimental and computational simulation based on cellular automata was proposed to represent the fibroblast adhesion on substrates and changes in a macro-scale observed in the cell during the adhesion process. The approach showed to be simple and efficient.

Transcriptional Analysis of Tendril and Inflorescence Development in Grapevine (Vitis vinifera L.)

PubMed Central

Díaz-Riquelme, José; Martínez-Zapater, José M.; Carmona, María J.

2014-01-01

In grapevine (Vitis vinifera L.), the lateral meristem can give rise to either tendrils or inflorescences which are determined organs. To get insights into the processes of tendril and inflorescence development, we characterized the transcriptional variation taking place in both organs. The results of the global transcriptional analyses along tendril and inflorescence development suggested that these two homologous organs initially share a common transcriptional program related to cell proliferation and growth functions. In later developmental stages they showed organ specific gene expression programs related to the particular differentiation processes taking place in each organ. In this way, tendrils showed higher transcription of genes related to photosynthesis, hormone signaling and secondary metabolism than inflorescences, while inflorescences displayed higher transcriptional activity for genes encoding transcription factors, mainly those belonging to the MADS-box gene family. The expression profiles of selected transcription factors related with inflorescence and flower meristem identity and with flower organogenesis were generally conserved with respect to their homologs in model species. Regarding tendrils, it was interesting to find that genes related with reproductive development in other species were also recruited for grapevine tendril development. These results suggest a role for those genes in the regulation of basic cellular mechanisms common to both developmental processes. PMID:24637773

Usher syndrome: molecular links of pathogenesis, proteins and pathways.

PubMed

Kremer, Hannie; van Wijk, Erwin; Märker, Tina; Wolfrum, Uwe; Roepman, Ronald

2006-10-15

Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear and in photoreceptor cells of the retina. The localization of the Usher proteins and the phenotype in animal models indicate that the Usher protein complex is essential in the morphogenesis of the stereocilia bundle in hair cells and in the calycal processes of photoreceptor cells. In addition, the Usher proteins are important in the synaptic processes of both cell types. The association of other proteins with the complex indicates functional links to a number of basic cell-biological processes. Prominently present is the connection to the dynamics of the actin cytoskeleton, involved in cellular morphology, cell polarity and cell-cell interactions. The Usher protein complex can also be linked to the cadherins/catenins in the adherens junction-associated protein complexes, suggesting a role in cell polarity and tissue organization. A third link can be established to the integrin transmembrane signaling network. The Usher interactome, as outlined in this review, participates in pathways common in inner ear and retina that are disrupted in the Usher syndrome.

Generic framework for mining cellular automata models on protein-folding simulations.

PubMed

Diaz, N; Tischer, I

2016-05-13

Cellular automata model identification is an important way of building simplified simulation models. In this study, we describe a generic architectural framework to ease the development process of new metaheuristic-based algorithms for cellular automata model identification in protein-folding trajectories. Our framework was developed by a methodology based on design patterns that allow an improved experience for new algorithms development. The usefulness of the proposed framework is demonstrated by the implementation of four algorithms, able to obtain extremely precise cellular automata models of the protein-folding process with a protein contact map representation. Dynamic rules obtained by the proposed approach are discussed, and future use for the new tool is outlined.

Pretreatment of high solid microbial sludges

DOEpatents

Rivard, Christopher J.; Nagle, Nicholas J.

1998-01-01

A process and apparatus for pretreating microbial sludges in order to enhance secondary anaerobic digestion. The pretreatment process involves disrupting the cellular integrity of municipal sewage sludge through a combination of thermal, explosive decompression and shear forces. The sludge is pressurized and pumped to a pretreatment reactor where it is mixed with steam to heat and soften the sludge. The pressure of the sludge is suddenly reduced and explosive decompression forces are imparted which partially disrupt the cellular integrity of the sludge. Shear forces are then applied to the sludge to further disrupt the cellular integrity of the sludge. Disrupting cellular integrity releases both soluble and insoluble organic constituents and thereby renders municipal sewage sludge more amenable to secondary anaerobic digestion.

Magnetization reversal process in (Sm, Dy, Gd) (Co, Fe, Cu, Zr)z magnets with different cellular structures

NASA Astrophysics Data System (ADS)

Liu, Lei; Liu, Zhuang; Zhang, Xin; Feng, Yanping; Wang, Chunxiao; Sun, Yingli; Lee, Don; Yan, Aru; Wu, Qiong

2017-05-01

Magnetization reversal mechanism is found to vary with cellular structures by a comparative study of the magnetization processes of three (Sm, Dy, Gd) (Co, Fe, Cu, Zr)z magnets with different cellular structures. Analysis of domain walls, initial magnetization curves and recoil loops indicates that the morphology of cellular structure has a significant effect on the magnetization process, besides the obvious connection to the difference of domain energy density between cell boundary phase (CBP) and main phase. The magnetization of Sample 2 (with a moderate cell size and uniformly continuous CBPs) behaves as a strong coherence domain-wall pinning effect to the domain wall and lead to a highest coercivity in the magnet. The magnetization of Sample 1 (with thin and discontinuous CBPs) shows an inconsistent pinning effect to the domain wall while that of Sample 3 (with thick and aggregate CBPs) exhibits a two-phase separation magnetization. Both the two cases lead to lower coercivities. A simplified model is given as well to describe the relationships among cellular structure and magnetization behavior.

High-pressure freezing and freeze substitution of Arabidopsis for electron microscopy.

PubMed

Austin, Jotham R

2014-01-01

The objectives of electron microscopy ultrastructural studies are to examine cellular architecture and relate the cell's structural machinery to dynamic functional roles. This aspiration is difficult to achieve if specimens have not been adequately preserved in a "living state"; hence specimen preparation is of the utmost importance for the success of any electron micrographic study. High-pressure freezing (HPF)/freeze substitution (FS) has long been recognized as the primer technique for the preservation of ultrastructure in biological samples. In most cases a basic HPF/freeze substitution protocol is sufficient to obtain superior ultrastructural preservation and structural contrast, which allows one to use more advanced microscopy techniques such as 3D electron tomography. However, for plant tissues, which have a thick cell wall, large water-filled vacuoles, and air spaces (all of which are detrimental to cryopreservation), these basic HPF/FS protocols often yield undesirable results. In particular, ice crystal artifacts and the staining of membrane systems are often poorly or negatively stained, which make 3D segmentation of a tomogram difficult. To overcome these problems, various aspects of the HPF/FS protocol can be altered, including the cryo-filler(s) used, freeze substitution cocktail, and the resin infiltration process. This chapter will describe these modifications for the preparation of plant tissues for routine electron microscopic studies, immunocytochemistry, and 3D tomographic electron imaging.

Basic Functional Capabilities for a Military Message Processing Service

DTIC Science & Technology

1974-09-01

AD-AiI1 166 BASIC FUNCTIONA’. CAPABILITIES FOR A MILITARY MESSAGE PROCESSING SERVICE Ronald Tugender, et al University of Southern California...Itte) S. TYPE OF REPORT & PERIOD COVERED BASIC FUNCTIONAL CAPABILITIES FOR A Research Report MILITARY MESSAGE PROCESSING SERVICE 6. PERFORMING ONG...WOROD (Conionwo m trevre aide If tneeoooy arm idmentify by egekA INber) automated message processing , command and control, writer-to-reader service

Coping with the Bounds: Speculations on Nonlinearity in Military Affairs

DTIC Science & Technology

2003-08-01

organizing criticality, cellular automata, solitons, and so on–because they all globally share this property . Nonlinearity reflects the science of the...Why does it matter? One rea- son for emphasizing nonlinearity is that it constitutes the well-established mathematical property underlying and making...have some hints as to what those principles might be.3 Complex adaptive systems, or cas, contain seven basic attributes. These consist of four properties

Cellular proliferation and regeneration following tissue damage. Progress report. [Eyes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harding, C.V.

1976-10-01

Results are reported from a study of wound healing in tissues of the eye, particularly lens, cornea, and surrounding tissues. The reactions of these tissues to mechanical injuries, as well as injuries induced by chemotoxic agents were studied. It is postulated that a better understanding of the basic reactions of the eye to injurious agents may be of importance in the evaluation of potential environmental hazards.

Basics for the preparation of quantum dots and their interactions with living cells.

PubMed

Jiang, Xiue; Bai, Jing; Wang, Tiantian

2014-01-01

A study of the interactions between nanoparticles and living cells is invaluable in understanding the nano-biological effect and the mechanism of cellular endocytosis. Here we describe two methods for the preparation of semiconductor quantum dots with different physiochemical properties. Furthermore, we describe how to study the interaction of the two quantum dots with living HeLa cells and red blood cells with confocal microscopy.

Learning Computers, Speaking English: Cooperative Activities for Learning English and Basic Word Processing.

ERIC Educational Resources Information Center

Quann, Steve; Satin, Diana

This textbook leads high-beginning and intermediate English-as-a-Second-Language (ESL) students through cooperative computer-based activities that combine language learning with training in basic computer skills and word processing. Each unit concentrates on a basic concept of word processing while also focusing on a grammar topic. Skills are…

Molecular and Cellular Biology Animations: Development and Impact on Student Learning

ERIC Educational Resources Information Center

McClean, Phillip; Johnson, Christina; Rogers, Roxanne; Daniels, Lisa; Reber, John; Slator, Brian M.; Terpstra, Jeff; White, Alan

2005-01-01

Educators often struggle when teaching cellular and molecular processes because typically they have only two-dimensional tools to teach something that plays out in four dimensions. Learning research has demonstrated that visualizing processes in three dimensions aids learning, and animations are effective visualization tools for novice learners…

Intercellular Communication by Exosome-Derived microRNAs in Cancer

PubMed Central

Hannafon, Bethany N.; Ding, Wei-Qun

2013-01-01

The development of human cancers is a multistep process in which normal cells acquire characteristics that ultimately lead to their conversion into cancer cells. Many obstacles must be overcome for this process to occur; of these obstacles, is the ability to survive an inhospitable microenvironment. It is recognized that the intercommunication between tumor cells and their surrounding microenvironment is essential to overcoming this obstacle and for the tumor to progress, metastasize and establish itself at distant sites. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication, as they carry lipids, proteins, mRNAs and microRNAs that can be transferred to a recipient cell via fusion of the exosome with the target cell membrane. In the context of cancer cells, this process entails the transfer of cancer-promoting cellular contents to surrounding cells within the tumor microenvironment or into the circulation to act at distant sites, thereby enabling cancer progression. In this process, the transfer of exosomal microRNAs to a recipient cell where they can regulate target gene expression is of particular interest, both in understanding the basic biology of cancer progression and for the development of therapeutic approaches. This review discusses the exosome-mediated intercellular communication via microRNAs within the tumor microenvironment in human cancers, with a particular focus on breast cancer exosomes. PMID:23839094

Microscopic Imaging and Spectroscopy with Scattered Light

PubMed Central

Boustany, Nada N.; Boppart, Stephen A.; Backman, Vadim

2012-01-01

Optical contrast based on elastic scattering interactions between light and matter can be used to probe cellular structure and dynamics, and image tissue architecture. The quantitative nature and high sensitivity of light scattering signals to subtle alterations in tissue morphology, as well as the ability to visualize unstained tissue in vivo, has recently generated significant interest in optical scatter based biosensing and imaging. Here we review the fundamental methodologies used to acquire and interpret optical scatter data. We report on recent findings in this field and present current advances in optical scatter techniques and computational methods. Cellular and tissue data enabled by current advances in optical scatter spectroscopy and imaging stand to impact a variety of biomedical applications including clinical tissue diagnosis, in vivo imaging, drug discovery and basic cell biology. PMID:20617940

Tissue morphodynamics shaping the early mouse embryo.

PubMed

Sutherland, Ann E

2016-07-01

Generation of the elongated vertebrate body plan from the initially radially symmetrical embryo requires comprehensive changes to tissue form. These shape changes are generated by specific underlying cell behaviors, coordinated in time and space. Major principles and also specifics are emerging, from studies in many model systems, of the cell and physical biology of how region-specific cell behaviors produce regional tissue morphogenesis, and how these, in turn, are integrated at the level of the embryo. New technical approaches have made it possible more recently, to examine the morphogenesis of the mouse embryo in depth, and to elucidate the underlying cellular mechanisms. This review focuses on recent advances in understanding the cellular basis for the early fundamental events that establish the basic form of the embryo. Copyright © 2016 Elsevier Ltd. All rights reserved.

GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation.

PubMed

Larijani, Bagher; Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

2015-01-01

Stem cell therapy seems a promising avenue in regenerative medicine. Within various stem cells, mesenchymal stem cells have progressively used for cellular therapy. Because of the age-related decreasing in the frequency and differentiating capacity of adult MSCs, fetal tissues such as fetal liver, lung, pancreas, spleen, etc. have been introduced as an alternative source of MSCs for cellular therapy. On the other hand, using stem cells as advanced therapy medicinal products, must be performed in compliance with cGMP as a quality assurance system to ensure the safety, quality, and identity of cell products during translation from the basic stem cell sciences into clinical cell transplantation. In this chapter the authors have demonstrated the manufacturing of GMP-grade human fetal liver-derived mesenchymal stem cells.

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

NASA Astrophysics Data System (ADS)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of cellular solids and make substantial contributions to the theoretical advance of impact dynamics.

Folding of guanine quadruplex molecules-funnel-like mechanism or kinetic partitioning? An overview from MD simulation studies.

PubMed

Šponer, Jiří; Bussi, Giovanni; Stadlbauer, Petr; Kührová, Petra; Banáš, Pavel; Islam, Barira; Haider, Shozeb; Neidle, Stephen; Otyepka, Michal

2017-05-01

Guanine quadruplexes (GQs) play vital roles in many cellular processes and are of much interest as drug targets. In contrast to the availability of many structural studies, there is still limited knowledge on GQ folding. We review recent molecular dynamics (MD) simulation studies of the folding of GQs, with an emphasis paid to the human telomeric DNA GQ. We explain the basic principles and limitations of all types of MD methods used to study unfolding and folding in a way accessible to non-specialists. We discuss the potential role of G-hairpin, G-triplex and alternative GQ intermediates in the folding process. We argue that, in general, folding of GQs is fundamentally different from funneled folding of small fast-folding proteins, and can be best described by a kinetic partitioning (KP) mechanism. KP is a competition between at least two (but often many) well-separated and structurally different conformational ensembles. The KP mechanism is the only plausible way to explain experiments reporting long time-scales of GQ folding and the existence of long-lived sub-states. A significant part of the natural partitioning of the free energy landscape of GQs comes from the ability of the GQ-forming sequences to populate a large number of syn-anti patterns in their G-tracts. The extreme complexity of the KP of GQs typically prevents an appropriate description of the folding landscape using just a few order parameters or collective variables. We reconcile available computational and experimental studies of GQ folding and formulate basic principles characterizing GQ folding landscapes. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

Ceratopteris richardii: a productive model for revealing secrets of signaling and development

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Roux, S. J.

2000-01-01

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

Ceratopteris richardii: a productive model for revealing secrets of signaling and development.

PubMed

Chatterjee, A; Roux, S J

2000-09-01

Ceratopteris richardii is an aquatic fern grown in tropical and subtropical regions of the world. It is proven to be a productive model system for studies in the genetics, biochemistry, and cell biology of basic biologic processes that occur in early gametophytic development. It provides several advantages to biologists, especially those interested in gravitational biology, polarity development, and in the genetics of sexual development. It is easy to culture, has a relatively short life cycle, and offers an array of attractive features that facilitate genetic studies. The germination and early development of large populations of genetically identical spores are easy to synchronize, and both the direction of polarity development and cell-level gravity responses can be measured and readily manipulated within the first 24 h of spore development. Although there is no reliable transformation system available yet in Ceratopteris, recent studies suggest that the technique of RNA interference can be used to block translation of specific genes in a related fern, Marsilea, and current studies will soon reveal the applicability of this approach, as well as of other transformation approaches, in Ceratopteris. A recently completed expressed sequence tag (EST) sequencing project makes available the partial sequence of more than 2000 cDNAs, representing a significant percentage of the genes being expressed during the first 24 h of spore germination, when many developmentally interesting processes are occurring. A microarray of these ESTs is being constructed, so especially for those scientists interested in basic cellular phenomena that occur early in spore germination, the availability of the ESTs and of the microarray will make Ceratopteris an even more attractive model system.

Establishment of a bilateral femoral large segmental bone defect mouse model potentially applicable to basic research in bone tissue engineering.

PubMed

Xing, Junchao; Jin, Huiyong; Hou, Tianyong; Chang, Zhengqi; Luo, Fei; Wang, Pinpin; Li, Zhiqiang; Xie, Zhao; Xu, Jianzhong

2014-12-01

To understand the cellular mechanism underlying bone defect healing in the context of tissue engineering, a reliable, reproducible, and standardized load-bearing large segmental bone defect model in small animals is indispensable. The aim of this study was to establish and evaluate a bilateral femoral defect model in mice. Donor mouse bone marrow mesenchymal stem cells (mBMSCs) were obtained from six mice (FVB/N) and incorporated into partially demineralized bone matrix scaffolds to construct tissue-engineered bones. In total, 36 GFP(+) mice were used for modeling. Titanium fixation plates with locking steel wires were attached to the femurs for stabilization, and 2-mm-long segmental bone defects were created in the bilateral femoral midshafts. The defects in the left and right femurs were transplanted with tissue-engineered bones and control scaffolds, respectively. The healing process was monitored by x-ray radiography, microcomputed tomography, and histology. The capacity of the transplanted mBMSCs to recruit host CD31(+) cells was investigated by immunofluorescence and real-time polymerase chain reaction. Postoperatively, no complication was observed, except that two mice died of unknown causes. Stable fixation of femurs and implants with full load bearing was achieved in all animals. The process of bone defect repair was significantly accelerated due to the introduction of mBMSCs. Moreover, the transplanted mBMSCs attracted more host CD31(+) endothelial progenitors into the grafts. The present study established a feasible, reproducible, and clinically relevant bilateral femoral large segmental bone defect mouse model. This model is potentially suitable for basic research in the field of bone tissue engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

3D Printing Variable Stiffness Foams Using Viscous Thread Instability

PubMed Central

Lipton, Jeffrey I.; Lipson, Hod

2016-01-01

Additive manufacturing of cellular structures has numerous applications ranging from fabrication of biological scaffolds and medical implants, to mechanical weight reduction and control over mechanical properties. Various additive manufacturing processes have been used to produce open regular cellular structures limited only by the resolution of the printer. These efforts have focused on printing explicitly designed cells or explicitly planning offsets between strands. Here we describe a technique for producing cellular structures implicitly by inducing viscous thread instability when extruding material. This process allows us to produce complex cellular structures at a scale that is finer than the native resolution of the printer. We demonstrate tunable effective elastic modulus and density that span two orders of magnitude. Fine grained cellular structures allow for fabrication of foams for use in a wide range of fields ranging from bioengineering, to robotics to food printing. PMID:27503148

Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes

PubMed Central

2004-01-01

14-3-3 proteins exert an extraordinarily widespread influence on cellular processes in all eukaryotes. They operate by binding to specific phosphorylated sites on diverse target proteins, thereby forcing conformational changes or influencing interactions between their targets and other molecules. In these ways, 14-3-3s ‘finish the job’ when phosphorylation alone lacks the power to drive changes in the activities of intracellular proteins. By interacting dynamically with phosphorylated proteins, 14-3-3s often trigger events that promote cell survival – in situations from preventing metabolic imbalances caused by sudden darkness in leaves to mammalian cell-survival responses to growth factors. Recent work linking specific 14-3-3 isoforms to genetic disorders and cancers, and the cellular effects of 14-3-3 agonists and antagonists, indicate that the cellular complement of 14-3-3 proteins may integrate the specificity and strength of signalling through to different cellular responses. PMID:15167810

The ubiquitin proteasomal system: a potential target for the management of Alzheimer's disease.

PubMed

Gadhave, Kundlik; Bolshette, Nityanand; Ahire, Ashutosh; Pardeshi, Rohit; Thakur, Krishan; Trandafir, Cristiana; Istrate, Alexandru; Ahmed, Sahabuddin; Lahkar, Mangala; Muresanu, Dafin F; Balea, Maria

2016-07-01

The cellular quality control system degrades abnormal or misfolded proteins and consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy and molecular chaperones. Any disturbance in this system causes proteins to accumulate, resulting in neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and prion or polyglutamine diseases. Alzheimer's disease is currently one of the most common age-related neurodegenerative diseases. However, its exact cause and pathogenesis are unknown. Currently approved medications for AD provide symptomatic relief; however, they fail to influence disease progression. Moreover, the components of the cellular quality control system represent an important focus for the development of targeted and potent therapies for managing AD. This review aims to evaluate whether existing evidence supports the hypothesis that UPS impairment causes the early pathogenesis of neurodegenerative disorders. The first part presents basic information about the UPS and its molecular components. The next part explains how the UPS is involved in neurodegenerative disorders. Finally, we emphasize how the UPS influences the management of AD. This review may help in the design of future UPS-related therapies for AD. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

An Acetylation Switch Regulates SUMO-Dependent Protein Interaction Networks

PubMed Central

Ullmann, Rebecca; Chien, Christopher D.; Avantaggiati, Maria Laura; Muller, Stefan

2013-01-01

SUMMARY The attachment of the SUMO modifier to proteins controls cellular signaling pathways through noncovalent binding to SUMO-interaction motifs (SIMs). Canonical SIMs contain a core of hydrophobic residues that bind to a hydrophobic pocket on SUMO. Negatively charged residues of SIMs frequently contribute to binding by interacting with a basic surface on SUMO. Here we define acetylation within this basic interface as a central mechanism for the control of SUMO-mediated interactions. The acetyl-mediated neutralization of basic charges on SUMO prevents binding to SIMs in PML, Daxx, and PIAS family members but does not affect the interaction between RanBP2 and SUMO. Acetylation is controlled by HDACs and attenuates SUMO- and PIAS-mediated gene silencing. Moreover, it affects the assembly of PML nuclear bodies and restrains the recruitment of the corepressor Daxx to these structures. This acetyl-dependent switch thus expands the regulatory repertoire of SUMO signaling and determines the selectivity and dynamics of SUMO-SIM interactions. PMID:22578841

Genetic etiology of oral cancer.

PubMed

Ali, Johar; Sabiha, Bibi; Jan, Hanif Ullah; Haider, Syed Adnan; Khan, Abid Ali; Ali, Saima S

2017-07-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. More than 90% of oral cancers (occurring in the mouth, lip, and tongue) are oral squamous cell carcinoma. The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. This high incidence occurs in correlation with oral cancer-associated behaviors such as alcohol, tobacco use. Researchers have reported that these behaviors lead to genetic variations in tumor suppressor genes (APC, p53), proto-oncogenes (Myc), oncogene (Ras) and genes controlling normal cellular processes (EIF3E, GSTM1). Processes such as segregation of chromosomes, genomic copy number, loss of heterozygosity, telomere stabilities, regulations of cell-cycle checkpoints, DNA damage repairs and defects in notch signaling pathways are involved in causing oral cancer. In order to develop preventive and therapeutic options, it is necessary to comprehend the basic molecular mechanisms forcing oral tumorigenesis. This review examines, in detail, the mechanisms of genetic alteration which are considered to be responsible for the initiation of oral cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of thiol-based redox switch processes in parasites - facts and future.

PubMed

Rahbari, Mahsa; Diederich, Kathrin; Becker, Katja; Krauth-Siegel, R Luise; Jortzik, Esther

2015-05-01

Malaria and African trypanosomiasis are tropical diseases caused by the protozoa Plasmodium and Trypanosoma, respectively. The parasites undergo complex life cycles in the mammalian host and insect vector, during which they are exposed to oxidative and nitrosative challenges induced by the host immune system and endogenous processes. Attacking the parasite's redox metabolism is a target mechanism of several known antiparasitic drugs and a promising approach to novel drug development. Apart from this aspect, oxidation of cysteine residues plays a key role in protein-protein interaction, metabolic responses to redox events, and signaling. Understanding the role and dynamics of reactive oxygen species and thiol switches in regulating cellular redox homeostasis is crucial for both basic and applied biomedical approaches. Numerous techniques have therefore been established to detect redox changes in parasites including biochemical methods, fluorescent dyes, and genetically encoded probes. In this review, we aim to give an insight into the characteristics of redox networks in the pathogens Plasmodium and Trypanosoma, including a comprehensive overview of the consequences of specific deletions of redox-associated genes. Furthermore, we summarize mechanisms and detection methods of thiol switches in both parasites and discuss their specificity and sensitivity.

Differentiation Driven Changes in the Dynamic Organization of Basal Transcription Initiation

PubMed Central

Giglia-Mari, Giuseppina; Mourgues, Sophie; Nonnekens, Julie; Andrieux, Lise O.; de Wit, Jan; Miquel, Catherine; Wijgers, Nils; Maas, Alex; Fousteri, Maria; Hoeijmakers, Jan H. J.; Vermeulen, Wim

2009-01-01

Studies based on cell-free systems and on in vitro–cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates and disassemble after reaction completion. This dynamic nature allows quick adaptation of transcription to changing conditions. However, it is unknown to what extent this dynamic transcription organization holds for postmitotic cells embedded in mammalian tissue. To allow analysis of transcription initiation dynamics directly into living mammalian tissues, we created a knock-in mouse model expressing fluorescently tagged TFIIH. Surprisingly and in contrast to what has been observed in cultured and proliferating cells, postmitotic murine cells embedded in their tissue exhibit a strong and long-lasting transcription-dependent immobilization of TFIIH. This immobilization is both differentiation driven and development dependent. Furthermore, although very statically bound, TFIIH can be remobilized to respond to new transcriptional needs. This divergent spatiotemporal transcriptional organization in different cells of the soma revisits the generally accepted highly dynamic concept of the kinetic framework of transcription and shows how basic processes, such as transcription, can be organized in a fundamentally different fashion in intact organisms as previously deduced from in vitro studies. PMID:19841728

Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.

PubMed

Rödel, Franz; Fournier, Claudia; Wiedemann, Julia; Merz, Felicitas; Gaipl, Udo S; Frey, Benjamin; Keilholz, Ludwig; Seegenschmiedt, M Heinrich; Rödel, Claus; Hehlgans, Stephanie

2017-01-01

For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.

Model-based analysis of keratin intermediate filament assembly

NASA Astrophysics Data System (ADS)

Martin, Ines; Leitner, Anke; Walther, Paul; Herrmann, Harald; Marti, Othmar

2015-09-01

The cytoskeleton of epithelial cells consists of three types of filament systems: microtubules, actin filaments and intermediate filaments (IFs). Here, we took a closer look at type I and type II IF proteins, i.e. keratins. They are hallmark constituents of epithelial cells and are responsible for the generation of stiffness, the cellular response to mechanical stimuli and the integrity of entire cell layers. Thereby, keratin networks constitute an important instrument for cells to adapt to their environment. In particular, we applied models to characterize the assembly of keratin K8 and K18 into elongated filaments as a means for network formation. For this purpose, we measured the length of in vitro assembled keratin K8/K18 filaments by transmission electron microscopy at different time points. We evaluated the experimental data of the longitudinal annealing reaction using two models from polymer chemistry: the Schulz-Zimm model and the condensation polymerization model. In both scenarios one has to make assumptions about the reaction process. We compare how well the models fit the measured data and thus determine which assumptions fit best. Based on mathematical modelling of experimental filament assembly data we define basic mechanistic properties of the elongation reaction process.

Nanobodies and recombinant binders in cell biology.

PubMed

Helma, Jonas; Cardoso, M Cristina; Muyldermans, Serge; Leonhardt, Heinrich

2015-06-08

Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. © 2015 Helma et al.

47 CFR 69.119 - Basic service element expedited approval process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Basic service element expedited approval process. 69.119 Section 69.119 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Computation of Charges § 69.119 Basic service element...

Teaching pathology in the 21st century. An experimental automated curriculum delivery system for basic pathology.

PubMed

Woods, J W; Jones, R R; Schoultz, T W; Kuenz, M; Moore, R L

1988-08-01

In late 1984, the "General Professional Education of the Physician" (GPEP) report recommended, among other things, that medical curricula be revised to rely less on lectures and more on independent study and problem solving. We seem to have anticipated, in 1980, the findings of the GPEP panel by formulating and starting to test the hypothesis that certain "core" information in medical curricula can be as effectively delivered by technology-based self-study means as by lecture or formal laboratory. We began, at that time, to prepare a series of self-study materials using, at first, videotape and then computer-controlled optical videodiscs. The content area selected for study was basic microscopic pathology. The series was planned to cover the following areas of study: cellular alterations and adaptations, cell injury, acute inflammation, chronic inflammation and wound healing, cellular accumulations, circulatory disturbances, necrosis, and neoplasia. All are intended to provide learning experiences in basic pathology. The first two programs were released for testing in 1983 as a two-sided videodisc accompanied by computer-driven pretests, study modules, and posttests that used Apple computers and Pioneer (DiscoVision) videodisc players. An MS DOS (eg, IBM) version of the computer programs was released in 1984. The first two programs are now used in 57 US, Canadian, European, and Philippine health professions schools, and over 1300 student and faculty evaluations have been received. Student and faculty evaluations of these first two programs were very positive, and, as a result, the others are in production and will be completed in 1988. Only when a critical mass of curriculum is available can we really test our stated hypothesis. In the meantime, it is worthwhile to report the evaluation of the first two programs.

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

PubMed Central

Traish, Abdulmaged M.; Goldstein, Irwin; Kim, Noel N.

2007-01-01

Objectives Androgens are essential for the development and growth of the penis, and they regulate erectile physiology by multiple mechanisms. Our goal is to provide a concise overview of the basic research and how this knowledge can be translated into a new clinical paradigm for patient management. In addition, this new paradigm may serve as a basis for stimulating constructive debate regarding the use of testosterone in men, and to promote new, innovative basic and clinical research to further understand the underlying mechanisms of androgen action in restoring erectile physiology. Methods A literature review was performed utilizing the US National Library of Medicine's PubMed database. Results On the basis of evidence derived from laboratory animal studies and clinical data, we postulate that androgen insufficiency disrupts cellular-signaling pathways and produces pathologic alterations in penile tissues, leading to erectile dysfunction. In this review, we discuss androgen-dependent cellular, molecular, and physiologic mechanisms modulating erectile function in the animal model, and the implication of this knowledge in testosterone use in the clinical setting to treat erectile dysfunction. The new clinical paradigm incorporates many of the consensed points of view discussed in traditional consensed algorithms exclusively designed for men with androgen insufficiency. There are, however, novel and innovative differences with this new clinical paradigm. This paradigm represents a fresh effort to provide mandatory and optional management strategies for men with both androgen insufficiency and erectile dysfunction. Conclusions The new clinical paradigm is evidence-based and represents one of the first attempts to address a logical management plan for men with concomitant hormonal and sexual health concerns. PMID:17329016

Quantum-Dot Cellular Automata

NASA Astrophysics Data System (ADS)

Snider, Gregory

2000-03-01

Quantum-dot Cellular Automata (QCA) [1] is a promising architecture which employs quantum dots for digital computation. It is a revolutionary approach that holds the promise of high device density and low power dissipation. A basic QCA cell consists of four quantum dots coupled capacitively and by tunnel barriers. The cell is biased to contain two excess electrons within the four dots, which are forced to opposite "corners" of the four-dot cell by mutual Coulomb repulsion. These two possible polarization states of the cell will represent logic "0" and "1". Properly arranged, arrays of these basic cells can implement Boolean logic functions. Experimental results from functional QCA devices built of nanoscale metal dots defined by tunnel barriers will be presented. The experimental devices to be presented consist of Al islands, which we will call quantum dots, interconnected by tunnel junctions and lithographically defined capacitors. Aluminum/ aluminum-oxide/aluminum tunnel junctions were fabricated using a standard e-beam lithography and shadow evaporation technique. The experiments were performed in a dilution refrigerator at a temperature of 70 mK. The operation of a cell is evaluated by direct measurements of the charge state of dots within a cell as the input voltage is changed. The experimental demonstration of a functioning cell will be presented. A line of three cells demonstrates that there are no metastable switching states in a line of cells. A QCA majority gate will also be presented, which is a programmable AND/OR gate and represents the basic building block of QCA systems. The results of recent experiments will be presented. 1. C.S. Lent, P.D. Tougaw, W. Porod, and G.H. Bernstein, Nanotechnology, 4, 49 (1993).

Pretreatment of high solid microbial sludges

DOEpatents

Rivard, C.J.; Nagle, N.J.

1998-07-28

A process and apparatus are disclosed for pretreating microbial sludges in order to enhance secondary anaerobic digestion. The pretreatment process involves disrupting the cellular integrity of municipal sewage sludge through a combination of thermal, explosive decompression and shear forces. The sludge is pressurized and pumped to a pretreatment reactor where it is mixed with steam to heat and soften the sludge. The pressure of the sludge is suddenly reduced and explosive decompression forces are imparted which partially disrupt the cellular integrity of the sludge. Shear forces are then applied to the sludge to further disrupt the cellular integrity of the sludge. Disrupting cellular integrity releases both soluble and insoluble organic constituents and thereby renders municipal sewage sludge more amenable to secondary anaerobic digestion. 1 fig.

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

NASA Astrophysics Data System (ADS)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Single-cell protein secretomic signatures as potential correlates to tumor cell lineage evolution and cell–cell interaction

PubMed Central

Kwak, Minsuk; Mu, Luye; Lu, Yao; Chen, Jonathan J.; Brower, Kara; Fan, Rong

2013-01-01

Secreted proteins including cytokines, chemokines, and growth factors represent important functional regulators mediating a range of cellular behavior and cell–cell paracrine/autocrine signaling, e.g., in the immunological system (Rothenberg, 2007), tumor microenvironment (Hanahan and Weinberg, 2011), or stem cell niche (Gnecchi etal., 2008). Detection of these proteins is of great value not only in basic cell biology but also for diagnosis and therapeutic monitoring of human diseases such as cancer. However, due to co-production of multiple effector proteins from a single cell, referred to as polyfunctionality, it is biologically informative to measure a panel of secreted proteins, or secretomic signature, at the level of single cells. Recent evidence further indicates that a genetically identical cell population can give rise to diverse phenotypic differences (Niepel etal., 2009). Non-genetic heterogeneity is also emerging as a potential barrier to accurate monitoring of cellular immunity and effective pharmacological therapies (Cohen etal., 2008; Gascoigne and Taylor, 2008), but can hardly assessed using conventional approaches that do not examine cellular phenotype at the functional level. It is known that cytokines, for example, in the immune system define the effector functions and lineage differentiation of immune cells. In this article, we hypothesize that protein secretion profile may represent a universal measure to identify the definitive correlate in the larger context of cellular functions to dissect cellular heterogeneity and evolutionary lineage relationship in human cancer. PMID:23390614

Transcriptome of Pneumocystis carinii during fulminate infection: carbohydrate metabolism and the concept of a compatible parasite.

PubMed

Cushion, Melanie T; Smulian, A George; Slaven, Bradley E; Sesterhenn, Tom; Arnold, Jonathan; Staben, Chuck; Porollo, Aleksey; Adamczak, Rafal; Meller, Jarek

2007-05-09

Members of the genus Pneumocystis are fungal pathogens that cause pneumonia in a wide variety of mammals with debilitated immune systems. Little is known about their basic biological functions, including life cycle, since no species can be cultured continuously outside the mammalian lung. To better understand the pathological process, about 4500 ESTS derived from sequencing of the poly(A) tail ends of P. carinii mRNAs during fulminate infection were annotated and functionally characterized as unassembled reads, and then clustered and reduced to a unigene set with 1042 members. Because of the presence of sequences from other microbial genomes and the rat host, the analysis and compression to a unigene set was necessarily an iterative process. BLASTx analysis of the unassembled reads (UR) vs. the Uni-Prot and TREMBL databases revealed 56% had similarities to existing polypeptides at E values of

Transcriptome of Pneumocystis carinii during Fulminate Infection: Carbohydrate Metabolism and the Concept of a Compatible Parasite

PubMed Central

Sesterhenn, Tom; Arnold, Jonathan; Staben, Chuck; Porollo, Aleksey; Adamczak, Rafal; Meller, Jarek

2007-01-01

Members of the genus Pneumocystis are fungal pathogens that cause pneumonia in a wide variety of mammals with debilitated immune systems. Little is known about their basic biological functions, including life cycle, since no species can be cultured continuously outside the mammalian lung. To better understand the pathological process, about 4500 ESTS derived from sequencing of the poly(A) tail ends of P. carinii mRNAs during fulminate infection were annotated and functionally characterized as unassembled reads, and then clustered and reduced to a unigene set with 1042 members. Because of the presence of sequences from other microbial genomes and the rat host, the analysis and compression to a unigene set was necessarily an iterative process. BLASTx analysis of the unassembled reads (UR) vs. the Uni-Prot and TREMBL databases revealed 56% had similarities to existing polypeptides at E values of≤10−6, with the remainder lacking any significant homology. The most abundant transcripts in the UR were associated with stress responses, energy production, transcription and translation. Most (70%) of the UR had similarities to proteins from filamentous fungi (e.g., Aspergillus, Neurospora) and existing P. carinii gene products. In contrast, similarities to proteins of the yeast-like fungi, Schizosaccharomyces pombe and Saccharomyces cerevisiae, predominated in the unigene set. Gene Ontology analysis using BLAST2GO revealed P. carinii dedicated most of its transcripts to cellular and physiological processes (∼80%), molecular binding and catalytic activities (∼70%), and were primarily derived from cell and organellar compartments (∼80%). KEGG Pathway mapping showed the putative P. carinii genes represented most standard metabolic pathways and cellular processes, including the tricarboxylic acid cycle, glycolysis, amino acid biosynthesis, cell cycle and mitochondrial function. Several gene homologs associated with mating, meiosis, and sterol biosynthesis in fungi were identified. Genes encoding the major surface glycoprotein family (MSG), heat shock (HSP70), and proteases (PROT/KEX) were the most abundantly expressed of known P. carinii genes. The apparent presence of many metabolic pathways in P. carinii, sexual reproduction within the host, and lack of an invasive infection process in the immunologically intact host suggest members of the genus Pneumocystis may be adapted parasites and have a compatible relationship with their mammalian hosts. This study represents the first characterization of the expressed genes of a non-culturable fungal pathogen of mammals during the infective process. PMID:17487271

The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors

PubMed Central

Matias, Pedro M.; Baek, Sung Hee; Bandeiras, Tiago M.; Dutta, Anindya; Houry, Walid A.; Llorca, Oscar; Rosenbaum, Jean

2015-01-01

Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10–12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models. PMID:25988184

Yeast Genomics for Bread, Beer, Biology, Bucks and Breath

NASA Astrophysics Data System (ADS)

Sakharkar, Kishore R.; Sakharkar, Meena K.

The rapid advances and scale up of projects in DNA sequencing dur ing the past two decades have produced complete genome sequences of several eukaryotic species. The versatile genetic malleability of the yeast, and the high degree of conservation between its cellular processes and those of human cells have made it a model of choice for pioneering research in molecular and cell biology. The complete sequence of yeast genome has proven to be extremely useful as a reference towards the sequences of human and for providing systems to explore key gene functions. Yeast has been a ‘legendary model’ for new technologies and gaining new biological insights into basic biological sciences and biotechnology. This chapter describes the awesome power of yeast genetics, genomics and proteomics in understanding of biological function. The applications of yeast as a screening tool to the field of drug discovery and development are highlighted and the traditional importance of yeast for bakers and brewers is discussed.

A Summary of the Biological Basis of Frailty.

PubMed

Fielding, Roger A

2015-01-01

Frailty has been defined as a geriatric syndrome that is characterized by a reduction in the physiological reserve required for an individual to respond to endogenous and exogenous stressors. Using a discrete definition of frailty that includes sedentariness, involuntary weight loss, fatigue, poor muscle strength, and slow gait speed, 'frailty' has been associated with increased disability, postsurgical complications, and increased mortality. Despite the strong associations between frailty and subsequent poor outcomes, limited attention to this common geriatric condition has been paid in clinical settings. A more fundamental basic understanding of the biological factors that contribute to the frailty phenotype has begun to emerge. Multiple underlying biological factors such as dysregulation of inflammatory processes, genomic instability, oxidative stress, mitochondrial dysfunction, and cellular senescence appear to contribute to the clinical presentation of frailty. This chapter summarizes the papers presented on the biological basis of frailty from the 83rd Nestlé Nutrition Institute Workshop on 'Frailty, Pathophysiology, Phenotype and Patient Care' held in Barcelona, Spain, in March 2014. © 2015 Nestec Ltd., Vevey/S. Karger AG, Basel.

High-Throughput Assessment of Cellular Mechanical Properties.

PubMed

Darling, Eric M; Di Carlo, Dino

2015-01-01

Traditionally, cell analysis has focused on using molecular biomarkers for basic research, cell preparation, and clinical diagnostics; however, new microtechnologies are enabling evaluation of the mechanical properties of cells at throughputs that make them amenable to widespread use. We review the current understanding of how the mechanical characteristics of cells relate to underlying molecular and architectural changes, describe how these changes evolve with cell-state and disease processes, and propose promising biomedical applications that will be facilitated by the increased throughput of mechanical testing: from diagnosing cancer and monitoring immune states to preparing cells for regenerative medicine. We provide background about techniques that laid the groundwork for the quantitative understanding of cell mechanics and discuss current efforts to develop robust techniques for rapid analysis that aim to implement mechanophenotyping as a routine tool in biomedicine. Looking forward, we describe additional milestones that will facilitate broad adoption, as well as new directions not only in mechanically assessing cells but also in perturbing them to passively engineer cell state.

Promise of new imaging technologies for assessing ovarian function.

PubMed

Singh, Jaswant; Adams, Gregg P; Pierson, Roger A

2003-10-15

Advancements in imaging technologies over the last two decades have ushered a quiet revolution in research approaches to the study of ovarian structure and function. The most significant changes in our understanding of the ovary have resulted from the use of ultrasonography which has enabled sequential analyses in live animals. Computer-assisted image analysis and mathematical modeling of the dynamic changes within the ovary has permitted exciting new avenues of research with readily quantifiable endpoints. Spectral, color-flow and power Doppler imaging now facilitate physiologic interpretations of vascular dynamics over time. Similarly, magnetic resonance imaging (MRI) is emerging as a research tool in ovarian imaging. New technologies, such as three-dimensional ultrasonography and MRI, ultrasound-based biomicroscopy and synchrotron-based techniques each have the potential to enhance our real-time picture of ovarian function to the near-cellular level. Collectively, information available in ultrasonography, MRI, computer-assisted image analysis and mathematical modeling heralds a new era in our understanding of the basic processes of female and male reproduction.

Lessons from natural and artificial polyploids in higher plants.

PubMed

Hegarty, M; Coate, J; Sherman-Broyles, S; Abbott, R; Hiscock, S; Doyle, J

2013-01-01

Polyploidy in higher plants is a major source of genetic novelty upon which selection may act to drive evolution, as evidenced by the widespread success of polyploid species in the wild. However, research into the effects of polyploidy can be confounded by the entanglement of several processes: genome duplication, hybridisation (allopolyploidy is frequent in plants) and subsequent evolution. The discovery of the chemical agent colchicine, which can be used to produce artificial polyploids on demand, has enabled scientists to unravel these threads and understand the complex genomic changes involved in each. We present here an overview of lessons learnt from studies of natural and artificial polyploids, and from comparisons between the 2, covering basic cellular and metabolic consequences through to alterations in epigenetic gene regulation, together with 2 in-depth case studies in Senecio and Glycine. See also the sister article focusing on animals by Arai and Fujimoto in this themed issue. Copyright © 2013 S. Karger AG, Basel.

Quantification of nanowire penetration into living cells

NASA Astrophysics Data System (ADS)

Xu, Alexander M.; Aalipour, Amin; Leal-Ortiz, Sergio; Mekhdjian, Armen H.; Xie, Xi; Dunn, Alexander R.; Garner, Craig C.; Melosh, Nicholas A.

2014-04-01

High-aspect ratio nanostructures such as nanowires and nanotubes are a powerful new tool for accessing the cell interior for delivery and sensing. Controlling and optimizing cellular access is a critical challenge for this new technology, yet even the most basic aspect of this process, whether these structures directly penetrate the cell membrane, is still unknown. Here we report the first quantification of hollow nanowires—nanostraws—that directly penetrate the membrane by observing dynamic ion delivery from each 100-nm diameter nanostraw. We discover that penetration is a rare event: 7.1±2.7% of the nanostraws penetrate the cell to provide cytosolic access for an extended period for an average of 10.7±5.8 penetrations per cell. Using time-resolved delivery, the kinetics of the first penetration event are shown to be adhesion dependent and coincident with recruitment of focal adhesion-associated proteins. These measurements provide a quantitative basis for understanding nanowire-cell interactions, and a means for rapidly assessing membrane penetration.

Illumination of growth, division and secretion by metabolic labeling of the bacterial cell surface

PubMed Central

Siegrist, M. Sloan; Swarts, Benjamin M.; Fox, Douglas M.; Lim, Shion An; Bertozzi, Carolyn R.

2015-01-01

The cell surface is the essential interface between a bacterium and its surroundings. Composed primarily of molecules that are not directly genetically encoded, this highly dynamic structure accommodates the basic cellular processes of growth and division as well as the transport of molecules between the cytoplasm and the extracellular milieu. In this review, we describe aspects of bacterial growth, division and secretion that have recently been uncovered by metabolic labeling of the cell envelope. Metabolite derivatives can be used to label a variety of macromolecules, from proteins to non-genetically-encoded glycans and lipids. The embedded metabolite enables precise tracking in time and space, and the versatility of newer chemoselective detection methods offers the ability to execute multiple experiments concurrently. In addition to reviewing the discoveries enabled by metabolic labeling of the bacterial cell envelope, we also discuss the potential of these techniques for translational applications. Finally, we offer some guidelines for implementing this emerging technology. PMID:25725012

Drosophila wing imaginal discs respond to mechanical injury via slow InsP3R-mediated intercellular calcium waves

NASA Astrophysics Data System (ADS)

Restrepo, Simon; Basler, Konrad

2016-08-01

Calcium signalling is a highly versatile cellular communication system that modulates basic functions such as cell contractility, essential steps of animal development such as fertilization and higher-order processes such as memory. We probed the function of calcium signalling in Drosophila wing imaginal discs through a combination of ex vivo and in vivo imaging and genetic analysis. Here we discover that wing discs display slow, long-range intercellular calcium waves (ICWs) when mechanically stressed in vivo or cultured ex vivo. These slow imaginal disc intercellular calcium waves (SIDICs) are mediated by the inositol-3-phosphate receptor, the endoplasmic reticulum (ER) calcium pump SERCA and the key gap junction component Inx2. The knockdown of genes required for SIDIC formation and propagation negatively affects wing disc recovery after mechanical injury. Our results reveal a role for ICWs in wing disc homoeostasis and highlight the utility of the wing disc as a model for calcium signalling studies.

Polyploidization in liver tissue.

PubMed

Gentric, Géraldine; Desdouets, Chantal

2014-02-01

Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue differentiation and, therefore, possibly a gain of function; alternately, it can be associated with development of disease, such as cancer. Polyploidy can occur because of cell fusion or abnormal cell division (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a common characteristic of the mammalian liver. Polyploidization occurs mainly during liver development, but also in adults with increasing age or because of cellular stress (eg, surgical resection, toxic exposure, or viral infections). This review will explore the mechanisms that lead to the development of polyploid cells, our current state of understanding of how polyploidization is regulated during liver growth, and its consequence on liver function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Developmental Gene Regulation and Mechanisms of Evolution

NASA Technical Reports Server (NTRS)

1998-01-01

The Marine Biological Laboratory and the National Aeronautics and Space Administration have established a cooperative agreement with the formation of a Center for Advanced Studies 'in the Space Life Sciences (CASSLS) at the MBL. This Center serves as an interface between NASA and the basic science community, addressing issues of mutual interest. The Center for Advanced Studies 'in the Space Life Sciences provides a forum for scientists to think and discuss, often for the first time, the role that gravity and aspects of spaceflight may play 'in fundamental cellular and physiologic processes. In addition the Center will sponsor discussions on evolutionary biology. These interactions will inform the community of research opportunities that are of interest to NASA. This workshop is one of a series of symposia, workshops and seminars that will be held at the MBL to advise NASA on a wide variety of topics in the life sciences, including cell biology, developmental biology, mg evolutionary biology, molecular biology, neurobiology, plant biology and systems biology.

Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways

PubMed Central

Wimmer, Peter; Schreiner, Sabrina

2015-01-01

Posttranslational modifications (PTMs) of proteins include enzymatic changes by covalent addition of cellular regulatory determinants such as ubiquitin (Ub) and small ubiquitin-like modifier (SUMO) moieties. These modifications are widely used by eukaryotic cells to control the functional repertoire of proteins. Over the last decade, it became apparent that the repertoire of ubiquitiylation and SUMOylation regulating various biological functions is not restricted to eukaryotic cells, but is also a feature of human virus families, used to extensively exploit complex host-cell networks and homeostasis. Intriguingly, besides binding to host SUMO/Ub control proteins and interfering with the respective enzymatic cascade, many viral proteins mimic key regulatory factors to usurp this host machinery and promote efficient viral outcomes. Advanced detection methods and functional studies of ubiquitiylation and SUMOylation during virus-host interplay have revealed that human viruses have evolved a large arsenal of strategies to exploit these specific PTM processes. In this review, we highlight the known viral analogs orchestrating ubiquitin and SUMO conjugation events to subvert and utilize basic enzymatic pathways. PMID:26343706

Complexity in Nature and Society: Complexity Management in the Age of Globalization

NASA Astrophysics Data System (ADS)

Mainzer, Klaus

The theory of nonlinear complex systems has become a proven problem-solving approach in the natural sciences from cosmic and quantum systems to cellular organisms and the brain. Even in modern engineering science self-organizing systems are developed to manage complex networks and processes. It is now recognized that many of our ecological, social, economic, and political problems are also of a global, complex, and nonlinear nature. What are the laws of sociodynamics? Is there a socio-engineering of nonlinear problem solving? What can we learn from nonlinear dynamics for complexity management in social, economic, financial and political systems? Is self-organization an acceptable strategy to handle the challenges of complexity in firms, institutions and other organizations? It is a main thesis of the talk that nature and society are basically governed by nonlinear and complex information dynamics. How computational is sociodynamics? What can we hope for social, economic and political problem solving in the age of globalization?.

DOT1L and H3K79 Methylation in Transcription and Genomic Stability.

PubMed

Wood, Katherine; Tellier, Michael; Murphy, Shona

2018-02-27

The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.

The U24 Protein from Human Herpesvirus 6 and 7 Affects Endocytic Recycling▿

PubMed Central

Sullivan, Brian M.; Coscoy, Laurent

2010-01-01

Modulation of T-cell receptor expression and signaling is essential to the survival of many viruses. The U24 protein expressed by human herpesvirus 6A, a ubiquitous human pathogen, has been previously shown to downregulate the T-cell receptor. Here, we show that U24 also mediates cell surface downregulation of a canonical early endosomal recycling receptor, the transferrin receptor, indicating that this viral protein acts by blocking early endosomal recycling. We present evidence that U24 is a C-tail-anchored protein that is dependent for its function on TRC40/Asna-1, a component of a posttranslational membrane insertion pathway. Finally, we find that U24 proteins from other roseoloviruses have a similar genetic organization and a conserved function that is dependent on a proline-rich motif. Inhibition of a basic cellular process by U24 has interesting implications not only for the pathogenicity of roseoloviruses but also for our understanding of the biology of endosomal transport. PMID:19923186

The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.

PubMed

Matias, Pedro M; Baek, Sung Hee; Bandeiras, Tiago M; Dutta, Anindya; Houry, Walid A; Llorca, Oscar; Rosenbaum, Jean

2015-01-01

Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.

The physics of lipid droplet nucleation, growth and budding.

PubMed

Thiam, Abdou Rachid; Forêt, Lionel

2016-08-01

Lipid droplets (LDs) are intracellular oil-in-water emulsion droplets, covered by a phospholipid monolayer and mainly present in the cytosol. Despite their important role in cellular metabolism and growing number of newly identified functions, LD formation mechanism from the endoplasmic reticulum remains poorly understood. To form a LD, the oil molecules synthesized in the ER accumulate between the monolayer leaflets and induce deformation of the membrane. This formation process works through three steps: nucleation, growth and budding, exactly as in phase separation and dewetting phenomena. These steps involve sequential biophysical membrane remodeling mechanisms for which we present basic tools of statistical physics, membrane biophysics, and soft matter science underlying them. We aim to highlight relevant factors that could control LD formation size, site and number through this physics description. An emphasis will be given to a currently underestimated contribution of the molecular interactions between lipids to favor an energetically costless mechanism of LD formation. Copyright © 2016 Elsevier B.V. All rights reserved.

Tetrahelical structural family adopted by AGCGA-rich regulatory DNA regions

NASA Astrophysics Data System (ADS)

Kocman, Vojč; Plavec, Janez

2017-05-01

Here we describe AGCGA-quadruplexes, an unexpected addition to the well-known tetrahelical families, G-quadruplexes and i-motifs, that have been a focus of intense research due to their potential biological impact in G- and C-rich DNA regions, respectively. High-resolution structures determined by solution-state nuclear magnetic resonance (NMR) spectroscopy demonstrate that AGCGA-quadruplexes comprise four 5'-AGCGA-3' tracts and are stabilized by G-A and G-C base pairs forming GAGA- and GCGC-quartets, respectively. Residues in the core of the structure are connected with edge-type loops. Sequences of alternating 5'-AGCGA-3' and 5'-GGG-3' repeats could be expected to form G-quadruplexes, but are shown herein to form AGCGA-quadruplexes instead. Unique structural features of AGCGA-quadruplexes together with lower sensitivity to cation and pH variation imply their potential biological relevance in regulatory regions of genes responsible for basic cellular processes that are related to neurological disorders, cancer and abnormalities in bone and cartilage development.