BioArchitecture is a term used to describe the organization and regulation of biological space. It applies to the principles which govern the structure of molecules, polymers and mutiprotein complexes, organelles, membranes and their organization in the cytoplasm and the nucleus. It also covers the integration of cells into their three dimensional environment at the level of cell-matrix, cell-cell interactions, integration into tissue/organ structure and function and finally into the structure of the organism. This review will highlight studies at all these levels which are providing a new way to think about the relationship between the organization of biological space and the function of biological systems.
actin; cytoskeleton; microtubules; intermediate filaments; nuclear structure; protein folding; isoform sorting
Our recent paper examined how pelvic fins and their musculature form developmentally and how these mechanisms have evolved within the vertebrate lineage, a process fundamental to the tetrapod transition. The transition from the water onto the land is among one of the most well studied steps in the evolutionary history of vertebrates, yet the genetic basis of this evolutionary transition is little studied and ill-defined. The advent of these terrestrial species resulted in a shift in locomotor strategies from the rhythmic undulating muscles of the fish body to a reliance upon powerful weight bearing muscles of the limbs to generate movement. We demonstrated that the pelvic fin muscles of bony fish are generated by a mechanism that has features of both of limb/fin muscle formation in tetrapods and primitive cartilaginous fish. We hypothesize that the adoption of the fully derived mode of hindlimb muscle formation, was a further modification of the mode of development deployed to generate pelvic fin muscles, a shift in overall muscle bioarchitecture we believe was critical to the success of the tetrapod transition.
muscle; evolution; fin; limb; zebrafish; tetrapod
In an attempt to assess whether there are any characteristics which a majority of ordinary people regard as life-affirming or life-denying, a questionnaire was given to a pilot group of 167 respondents, representing three different age and social categories. Five life-affirming and five life-denying characteristics were mentioned by more than 10% of respondents. Of the former, Drive, Sociability, Happiness and Optimism were endorsed by 15-20%. Of the latter, Unsociability and Poor Coping were mentioned by 22%, making them distinctly more frequent than the following categories of Pessimism, Lack of Drive and Unhappiness (11-14%). It is suggested that a number of these subjectively determined characteristics, which the general public perceive as being life-affirming or denying, do indeed influence physical or mental health, illness or illness behaviour. It may therefore be of value to utilize this set of public perceptions in future programmes of health education.
A goal of biomimetic chemistry is to use the hierarchical architecture inherent in biological systems to guide the synthesis of functional three dimensional structures. Viruses and other highly symmetrical protein cage architectures provide defined scaffolds to initiate hierarchical structure assembly. Here we demonstrate that a crosslinked branched polymer can be initiated and synthesized within the interior cavity of a protein cage architecture. Creating this polymer network allows for the spatial control of pendant reactive sites and dramatically increases the stability of the cage architecture. This material was generated by the sequential coupling of multifunctional monomers using click chemistry to create a branched crosslinked polymer network. Analysis of polymer growth by mass spectrometry demonstrated that the polymer was initiated at the interior surface of the cage at genetically introduced cysteine reactive sites. The polymer grew as expected to generation 2.5 where it was limited by the size constraints of the cavity. The polymer network was fully crosslinked across protein subunits that make up the cage and extended the thermal stability for the cage to at least 120°C. The introduced reactive centers were shown to be active and their number density increased with increasing generation. This synthetic approach provides a new avenue for creating defined polymer networks, spatially constrained by a biological template.
To illustrate the feasibility of using hyperpolarized helium MRI (HPH-MRI) to obtain functional information which may assist in improving conformal avoidance of ventilating lung tissue during thoracic radiotherapy.
Methods and Materials
HPH-MRI images were obtained from a volunteer patient. These images were first fused with a proton density weighted (PDw) MRI to provide corresponding anatomic detail, then with the treatment planning CT of a patient from our treatment planning database who possessed equivalent thoracic dimensions. An optimized treatment plan was then generated using the TomoTherapy TPS, designating the HPH enhancing regions as Ventilation Volume (VV). A dose volume histogram compares the dosimetry of the lungs as a paired organ, the VV, and the lungs minus the VV. The clinical consequence of these changes were estimated using a bio-effect model, the parallel architecture model or local damage (fdam) model. Model parameters were chosen from published studies linking the incidence of grade 3+ pneumonitis with dose and volume irradiated.
For two hypothetical treatment plans of 60 Gy in 30 fractions delivered to a right upper lobe lung mass, one utilizing and one ignoring the Ventilation Volume as an avoidance structure, the NTDmean values for the lung subvolumes were as follows: lungs=12.5 Gy3 vs 13.52 Gy3, Ventilation Volume=9.94 Gy3 vs 13.95 Gy3, and lungs minus ventilation volume= 16.69 Gy3 vs 19.16 Gy3. Using the fdam values generated from these plans, one would predict a reduction of the incidence of Grade 3+ radiation pneumonitis from 12% to 4% when compared with a conventionally optimized plan.
The use of HPH-MRI to identify ventilated lung subvolumes is feasible, and has the potential to be incorporated into conformal avoidance treatment planning paradigms. A prospective clinical study evaluating this imaging technique is being developed.
Lung cancer; functional imaging; radiotherapy; image guidance; magnetic resonance imaging
For the past decade, motorcycle fatalities have risen while other motor vehicle fatalities have declined. Many motorcycle fatalities occurred within intersections after a driver failed to see a motorcyclist. However, little is known about the behavior of motorcyclists when they negotiate an intersection. A study was undertaken to compare the behavior at intersections of an experienced group of motorcyclists when they were operating a motorcycle with their behavior when they were driving a car. Each participant navigated a course through low-volume, open roads. Participants wore eye-tracking equipment to record eye-glance information, and the motorcycle and car were instrumented with an onboard accelerometer and Global Positioning System apparatus. Results showed that participants were more likely to make last glances toward the direction of the most threatening traffic before they made a turn when they were driving a car than when they were riding a motorcycle. In addition, motorcyclists were less likely to come to a complete stop at a stop sign than car drivers. These results suggested that motorcyclists were exposing themselves to unnecessary risk. Specifically, motorcyclists frequently failed to make proper glances and practice optimal riding techniques. The behavior of the motorcyclists was compared with the current Motorcycle Safety Foundation curriculum. The results suggested that threat-response and delayed-apex techniques should be added to the training curriculum.
There has been recent interest in treating large bone defects with polymer scaffolds because current modalities such as autographs and allographs have limitations. Additionally, polymer scaffolds are utilized in tissue engineering applications to implant and anchor tissues in place, promoting integration with surrounding native tissue. In both applications, rapid and increased bone growth is crucial to the success of the implant. Recent studies have shown that mimicking native bone tissue morphology leads to increased osteoblastic phenotype and more rapid mineralization. The purpose of this study was to compare bone ingrowth into polymer scaffolds created with a biomimetic porous architecture to those with a simple porous design. The biomimetic architecture was designed from the inverse structure of native trabecular bone and manufactured using solid free form fabrication. Histology and μCT analysis demonstrated a 500-600% increase in bone growth into and adjacent to the biomimetic scaffold at five months post-op. This is in agreement with previous studies in which biomimetic approaches accelerated bone formation. It also supports the applicability of polymer scaffolds for the treatment of large tissue defects when implanting tissue-engineering constructs.
scaffolds; μCT; histomorphometry; biomimetic; polybutylene terephthalate
The interface between the science and engineering of biology and materials is an area of growing interest. One of the goals of this field is to utilize biological synthesis and processing of polymers as a route to gain insight into topics such as molecular recognition, self-assembly and the formation of materials with well-defined architectures. The biological processes involved in polymer synthesis and assembly can offer important information on fundamental interactions involved in the formation of complex material architectures, as well as practical knowledge into new and important materials related to biomaterial uses and tissue engineering needs. Classic approaches in biology, including genetic engineering, controlled microbial physiology and enzymatic synthesis, are prototypical methods used to control polymer structure and chemistry, including stereoselectivity and regioselectivity, to degrees unattainable using traditional synthetic chemistry. This type of control can lead to detailed and systematic studies of the formation of the structural hierarchy in materials and the subsequent biological responses to these materials.
Results of several investigations indicate that eye movements can reveal memory for elements of previous experience. These effects of memory on eye movement behavior can emerge very rapidly, changing the efficiency and even the nature of visual processing without appealing to verbal reports and without requiring conscious recollection. This aspect of eye movement based memory investigations is particularly useful when eye movement methods are used with special populations (e.g., young children, elderly individuals, and patients with severe amnesia), and also permits use of comparable paradigms in animals and humans, helping to bridge different memory literatures and permitting cross-species generalizations. Unique characteristics of eye movement methods have produced findings that challenge long-held views about the nature of memory, its organization in the brain, and its failures in special populations. Recently, eye movement methods have been successfully combined with neuroimaging techniques such as fMRI, single-unit recording, and magnetoencephalography, permitting more sophisticated investigations of memory. Ultimately, combined use of eye-tracking with neuropsychological and neuroimaging methods promises to provide a more comprehensive account of brain–behavior relationships and adheres to the “converging evidence” approach to cognitive neuroscience.
eye movements; fMRI; MEG; memory; hippocampus; amnesia
The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.
Genetic association studies have rapidly become a major tool for identifying the genetic basis of common human diseases. The advent of cost-effective genotyping coupled with large collections of samples linked to clinical outcomes and quantitative traits now make it possible to systematically characterize genotype-phenotype relationships in diverse populations and extensive datasets. To capitalize on these advancements, the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) project, as part of the collaborative Population Architecture using Genomics and Epidemiology (PAGE) study, accesses two collections: the National Health and Nutrition Examination Surveys (NHANES) and BioVU, Vanderbilt University’s biorepository linked to de-identified electronic medical records. We describe herein the workflows for accessing and using the epidemiologic (NHANES) and clinical (BioVU) collections, where each workflow has been customized to reflect the content and data access limitations of each respective source. We also describe the process by which these data are generated, standardized, and shared for meta-analysis among the PAGE study sites. As a specific example of the use of BioVU, we describe the data mining efforts to define cases and controls for genetic association studies of common cancers in PAGE. Collectively, the efforts described here are a generalized outline for many of the successful approaches that can be used in the era of high-throughput genotype-phenotype associations for moving biomedical discovery forward to new frontiers of data generation and analysis.
One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure.
Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.
The BioMediator system developed at the University of Washington (UW) provides
a theoretical and practical foundation for data integration across
diverse biomedical research domains and various data types. In this
paper we demonstrate the generalizability of its architecture through
its application to the UW Human Brain Project (HBP) for understanding
language organization in the brain. We first describe the system architecture
and the characteristics of the four data sources developed
by the UW HBP. Second we present the process of developing the application
prototype for HBP neuroscience researchers posing queries across
these semantically and syntactically heterogeneous neurophysiologic data
sources. Then we discuss the benefits and potential limitations of
the BioMediator system as a general data integration solution for different
user groups in genomic and neuroscience research domains.
The desire to immobilize, encapsulate, or entrap viable cells for use in a variety of applications has been explored for decades. Traditionally, the approach is to immobilize cells to utilize a specific functionality of the cell in the system.
Scope of Review
This review describes our recent discovery that living cells can organize extended nanostructures and nano-objects to create a highly biocompatible nano//bio interface .
We find that short chain phospholipids direct the formation of thin film silica mesophases during evaporation-induced self-assembly (EISA) , and that the introduction of cells alter the self-assembly pathway. Cells organize an ordered lipid-membrane that forms a coherent interface with the silica mesophase that is unique in that it withstands drying - yet it maintains accessibility to molecules introduced into the 3D silica host. Cell viability is preserved in the absence of buffer, making these constructs useful as standalone cell-based sensors. In response to hyperosmotic stress, the cells release water, creating a pH gradient which is maintained within the nanostructured host and serves to localize lipids, proteins, plasmids, lipidized nanocrystals, and other components at the cellular surface. This active organization of the bio/nano interface can be accomplished during ink-jet printing or selective wetting - processes allowing patterning of cellular arrays - and even spatially-defined genetic modification.
Recent advances in the understanding of nanotechnology and cell biology encourage the pursuit of more complex endeavors where the dynamic interactions of the cell and host material act symbiotically to obtain new, useful functions.
BioPAX (Biological Pathway Exchange) is a standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data (http://www.biopax.org). Pathway data captures our understanding of biological processes, but its rapid growth necessitates development of databases and computational tools to aid interpretation. However, the current fragmentation of pathway information across many databases with incompatible formats presents barriers to its effective use. BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. BioPAX was created through a community process. Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available. Thus, large amounts of pathway data are available in a computable form to support visualization, analysis and biological discovery.
pathway data integration; pathway database; standard exchange format; ontology; information system
The general practitioner in Norway is expected to ensure equity and effectiveness through fair rationing. At the same time, due to recent reforms of the Norwegian health care sector, both the role of economic incentives and patient autonomy have been strengthened. Studies indicate that modern general practitioners, both in Norway and in other countries are uncomfortable with the gatekeeper role, but there is little knowledge about how general practitioners experience rationing in practice.
Through focus group interviews with Norwegian general practitioners, we explore physicians' attitudes toward factors of influence on medical decision making and how rationing dilemmas are experienced in everyday practice.
Four major concerns appeared in the group discussions: The obligation to ration health care, professional autonomy, patient autonomy, and competition. A central finding was that the physicians find rationing difficult because saying no in face to face relations often is felt uncomfortable and in conflict with other important objectives for the general practitioner.
It is important to understand the association between using economic incentives in the management of health care, increasing patient autonomy, and the willingness among physicians to contribute to efficient, fair and legitimate resource allocation.
Most tumors arise from epithelial tissues, such as mammary glands and lobules, and their initiation is associated with the disruption of a finely defined epithelial architecture. Progression from intraductal to invasive tumors is related to genetic mutations that occur at a subcellular level but manifest themselves as functional and morphological changes at the cellular and tissue scales, respectively. Elevated proliferation and loss of epithelial polarization are the two most noticeable changes in cell phenotypes during this process. As a result, many three-dimensional cultures of tumorigenic clones show highly aberrant morphologies when compared to regular epithelial monolayers enclosing the hollow lumen (acini). In order to shed light on phenotypic changes associated with tumor cells, we applied the bio-mechanical IBCell model of normal epithelial morphogenesis quantitatively matched to data acquired from the non-tumorigenic human mammary cell line, MCF10A. We then used a high-throughput simulation study to reveal how modifications in model parameters influence changes in the simulated architecture. Three parameters have been considered in our study, which define cell sensitivity to proliferative, apoptotic and cell-ECM adhesive cues. By mapping experimental morphologies of four MCF10A-derived cell lines carrying different oncogenic mutations onto the model parameter space, we identified changes in cellular processes potentially underlying structural modifications of these mutants. As a case study, we focused on MCF10A cells expressing an oncogenic mutant HER2-YVMA to quantitatively assess changes in cell doubling time, cell apoptotic rate, and cell sensitivity to ECM accumulation when compared to the parental non-tumorigenic cell line. By mapping in vitro mutant morphologies onto in silico ones we have generated a means of linking the morphological and molecular scales via computational modeling. Thus, IBCell in combination with 3D acini cultures can form a computational/experimental platform for suggesting the relationship between the histopathology of neoplastic lesions and their underlying molecular defects.
The majority of tumors arise in epithelial tissues that form monolayers of tightly packed cells enclosing the inner ductal or lobular cavities. Epithelial tumors (carcinomas) are associated with a disruption of epithelial architecture, such as filling of the inner lumen in the early stages of cancer, or the distortion of the ductal structure and spreading to the surrounding stroma in the subsequent invasive stages of tumor. Non-tumorigenic epithelial cells grown in 3D in vitro cultures form regular monolayered spheroids with hollow lumen (acini, Fig. 1a) resembling the architecture of normal epithelial cysts. In contrast, tumor cells taken from patients' biopsies and grown in 3D culture acquire various morphologies, often loosing the epithelial-like architecture. How these molecular defects produce such abnormal morphologies remains an open issue. We propose here to use the bio-mechanical model of epithelial morphogenesis, IBCell, to quantitatively investigate the phenotypical changes that the epithelial cells need to obtain in order to produce the aberrant morphologies observable experimentally and clinically. IBCell in combination with 3D acini cultures can form a computational/experimental platform for suggesting the link between histopathology of early tumors and underlying molecular defects.
Biocompatible synthetic polymers are largely used in the bio–medical domain, tissue engineering and in controlled release of medicines. Polymers can be used in the achievement of cardiac and vascular devices, mammary implants, eye lenses, surgical threads, nervous conduits, adhesives, blood substitutes, etc. Our study was axed on the development of cytotoxicity tests for 3 synthetic polymers, namely polyvinyl alcohol, polyethylene glycol and polyvinyl chloride. These tests targeted to determine the viability and morphology of cells (fibroblasts) that were in indirect contact with the studied polymers. Cell viability achieved for all the studied synthetic polymers allowed their frame in biocompatible material category. Cell morphology did not significantly change, thus accomplishing a new biocompatibility criterion. The degree of biocompatibility of the studied polymers varied. Polyvinyl alcohol presented the highest grade of biocompatibility and polyvinyl chloride placed itself at the lowest limit of biocompatibility. The results achieved allowed the selection of those polymers that (by enhancing their degrees of biocompatibility due to the association with various biopolymers) will be used in the development of new biocompatible materials, useful in nervous conduits manufacture.
Polyvinyl alcohol; polyethylenglycol; polyvinyl chloride; dermal fibroblasts; MTT test
Innovations in biological and biomedical imaging produce complex high-content and multivariate image data. For decision-making and generation of hypotheses, scientists need novel information technology tools that enable them to visually explore and analyze the data and to discuss and communicate results or findings with collaborating experts from various places.
In this paper, we present a novel Web2.0 approach, BioIMAX, for the collaborative exploration and analysis of multivariate image data by combining the webs collaboration and distribution architecture with the interface interactivity and computation power of desktop applications, recently called rich internet application.
BioIMAX allows scientists to discuss and share data or results with collaborating experts and to visualize, annotate, and explore multivariate image data within one web-based platform from any location via a standard web browser requiring only a username and a password. BioIMAX can be accessed at http://ani.cebitec.uni-bielefeld.de/BioIMAX with the username "test" and the password "test1" for testing purposes.
In an effort to identify previously unrecognized aspects of editorial decision-making, we explored the words and phrases that one group of editors used during their meetings.
We performed an observational study of discussions at manuscript meetings at JAMA, a major US general medical journal. One of us (KD) attended 12 editorial meetings in 2003 as a visitor and took notes recording phrases from discussion surrounding 102 manuscripts. In addition, editors attending the meetings completed a form for each manuscript considered, listing the reasons they were inclined to proceed to the next step in publication and reasons they were not (DR attended 4/12 meetings). We entered the spoken and written phrases into NVivo 2.0. We then developed a schema for classifying the editors' phrases, using an iterative approach.
Our classification schema has three main themes: science, journalism, and writing. We considered 2,463 phrases, of which 87 related mainly to the manuscript topic and were not classified (total 2,376 classified). Phrases related to science predominated (1,274 or 54%). The editors, most of whom were physicians, also placed major weight on goals important to JAMA's mission (journalism goals) such as importance to medicine, strategic emphasis for the journal, interest to the readership, and results (729 or 31% of phrases). About 16% (n = 373) of the phrases used related to writing issues, such as clarity and responses to the referees' comments.
Classification of editorial discourse provides insight into editorial decision making and concepts that need exploration in future studies.
Escherichia coli is one of the best studied microorganisms and finds multiple applications especially as tool in the heterologous production of interesting proteins of other organisms. The heterologous expression of special surface (S-) layer proteins caused the formation of extremely long E. coli cells which leave transparent tubes when they divide into single E. coli cells. Such natural structures are of high value as bio-templates for the development of bio-inorganic composites for many applications. In this study we used genetically modified filamentous Escherichia coli cells as template for the design of polyelectrolyte tubes that can be used as carrier for functional molecules or particles. Diversity of structures of biogenic materials has the potential to be used to construct inorganic or polymeric superior hybrid materials that reflect the form of the bio-template. Such bio-inspired materials are of great interest in diverse scientific fields like Biology, Chemistry and Material Science and can find application for the construction of functional materials or the bio-inspired synthesis of inorganic nanoparticles.
Genetically modified filamentous E. coli cells were fixed in 2% glutaraldehyde and coated with alternating six layers of the polyanion polyelectrolyte poly(sodium-4styrenesulfonate) (PSS) and polycation polyelectrolyte poly(allylamine-hydrochloride) (PAH). Afterwards we dissolved the E. coli cells with 1.2% sodium hypochlorite, thus obtaining hollow polyelectrolyte tubes of 0.7 μm in diameter and 5–50 μm in length. For functionalisation the polyelectrolyte tubes were coated with S-layer protein polymers followed by metallisation with Pd(0) particles. These assemblies were analysed with light microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and transmission electron microscopy.
The thus constructed new material offers possibilities for diverse applications like novel catalysts or metal nanowires for electrical devices. The novelty of this work is the use of filamentous E. coli templates and the use of S-layer proteins in a new material construct.
Escherichia coli; S-layer; Polyelectrolytes; Layer-by-layer (LbL); Palladium; SEM; TEM; Nanoparticle
The underlying goal of synthetic biology is to make the process of engineering biological systems easier. Recent work has focused on defining and developing standard biological parts. The technical standard that has gained the most traction in the synthetic biology community is the BioBrick standard for physical composition of genetic parts. Parts that conform to the BioBrick assembly standard are BioBrick standard biological parts. To date, over 2,000 BioBrick parts have been contributed to, and are available from, the Registry of Standard Biological Parts.
Here we extended the same advantages of BioBrick standard biological parts to the plasmid-based vectors that are used to provide and propagate BioBrick parts. We developed a process for engineering BioBrick vectors from BioBrick parts. We designed a new set of BioBrick parts that encode many useful vector functions. We combined the new parts to make a BioBrick base vector that facilitates BioBrick vector construction. We demonstrated the utility of the process by constructing seven new BioBrick vectors. We also successfully used the resulting vectors to assemble and propagate other BioBrick standard biological parts.
We extended the principles of part reuse and standardization to BioBrick vectors. As a result, myriad new BioBrick vectors can be readily produced from all existing and newly designed BioBrick parts. We invite the synthetic biology community to (1) use the process to make and share new BioBrick vectors; (2) expand the current collection of BioBrick vector parts; and (3) characterize and improve the available collection of BioBrick vector parts.
Cells divide and accurately inherit genomic and cellular content through synchronized changes in cellular organization and chromosome dynamics. Although DNA segregation, nuclear reformation and cytokinesis/abscission temporally overlap, little is known about how these distinct events are coordinated to ensure accurate cell division. Recently, we found that disruption of postmitotic nuclear pore complex assembly, an essential aspect of the newly forming nuclear envelope, triggers an Aurora B-dependent delay in abscission. This delay is further characterized by mislocalized, aberrantly active Aurora B in the cytoplasm of midbody-stage cells. These results support a model in which an Aurora B-mediated abscission checkpoint provides surveillance of nuclear pore complex formation to ensure that elements of nuclear architecture are fully formed before daughter cells are physically separated. Here we discuss the process of nuclear pore complex assembly, describe potential mechanisms that may explain how this process could be coordinated with abscission and postulate why such a checkpoint mechanism may exist.
abscission; aurora B; cytokinesis; nuclear basket; nuclear pore assembly; nuclear pore complex; Nup153; Nup50; Tpr
Estrogens and androgens play a key role in regulating bone mass. However, their clinical use as bone anabolic agents is limited due to unwanted side effects, particularly in reproductive organs. In 2002, the synthetic ligand estren was described to reproduce the bone anabolic, nongenotropic effects of sex steroids while having no effect on the uterus or seminal vesicles. But in the current issue of the JCI, Windahl et al. provide data showing that estrens are not as suitable a replacement for estrogen as was initially reported (see the related article beginning on page 2500). Though not catabolic, estrens triggered only minor, nonsignificant increases in bone mass in gonadectomized mice, all the while inducing hypertrophy of reproductive organs. Does this mean estrens should not be pursued as a therapy for osteoporosis?
Lactobacillus reuteri strain ATCC 55730 (LB BIO) was isolated as a pure culture from a Reuteri tablet purchased from the BioGaia company. This probiotic strain produces a soluble glucan (reuteran), in which the majority of the linkages are of the α-(1→4) glucosidic type (∼70%). This reuteran also contains α-(1→6)- linked glucosyl units and 4,6-disubstituted α-glucosyl units at the branching points. The LB BIO glucansucrase gene (gtfO) was cloned and expressed in Escherichia coli, and the GTFO enzyme was purified. The recombinant GTFO enzyme and the LB BIO culture supernatants synthesized identical glucan polymers with respect to linkage type and size distribution. GTFO thus is a reuteransucrase, responsible for synthesis of this reuteran polymer in LB BIO. The preference of GTFO for synthesizing α-(1→4) linkages is also evident from the oligosaccharides produced from sucrose with different acceptor substrates, e.g., isopanose from isomaltose. GTFO has a relatively high hydrolysis/transferase activity ratio. Complete conversion of 100 mM sucrose by GTFO nevertheless yielded large amounts of reuteran, although more than 50% of sucrose was converted into glucose. This is only the second example of the isolation and characterization of a reuteransucrase and its reuteran product, both found in different L. reuteri strains. GTFO synthesizes a reuteran with the highest amount of α-(1→4) linkages reported to date.