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
The first major hurdle for any new journal is to achieve acceptance into Medline/PubMed. I am pleased to report that BioArchitecture was accepted into Medline/PubMed in August 2012. This means that accepted manuscripts are immediately visible through their listing on PubMed. This is very welcome news to contributors to the journal and makes the journal a more attractive destination for publication of new research findings.
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
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.
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
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 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.
Bio-inspired material systems are derived from different living organisms such as plants, arthropods, mammals and marine organisms. These biomaterial systems from nature are always present in the form of composites, with molecular-scale interactions optimized to direct functional features. With interest in replacing synthetic materials with natural materials due to biocompatibility, sustainability and green chemistry issues, it is important to understand the molecular structure and chemistry of the raw component materials to also learn from their natural engineering, interfaces and interactions leading to durable and highly functional material architectures. This review will focus on applications of biomaterials in single material forms, as well as biomimetic composites inspired by natural organizational features. Examples of different natural composite systems will be described, followed by implementation of the principles underlying their composite organization into artificial bio-inspired systems for materials with new functional features for future medicine.
bio-inspired; cellulose; collagen; resilin; silk; SP1
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.
Aquifer microbial communities can be investigated using Bio-traps® (“bio-traps”), passive samplers containing Bio-Sep® beads (“bio-beads”) that are deployed in monitoring wells to be colonized by bacteria delivered via groundwater flow through the well. When bio-beads are “baited” with organic contaminants enriched in 13C, stable isotope probing allows assessment of the composition and activity of the microbial community. This study used an ex situ system fed by groundwater continuously extracted from an adjacent monitoring well within an experimentally-created aerobic zone treating a tert-butyl alcohol (TBA) plume. The goal was to evaluate aspects of bio-trap performance that cannot be studied quantitatively in situ. The measured groundwater flow through a bio-trap housing suggests that such traps might typically “sample” about 1.8 L per month. The desorption of TBA or methyl tert-butyl ether (MTBE) bait from bio-traps during a typical deployment duration of 6 weeks was approximately 90% and 45%, respectively, of the total initial bait load, with initially high rate of mass loss that decreased markedly after a few days. The concentration of TBA in groundwater flowing by the TBA-baited bio-beads was estimated to be as high as 3400 mg/L during the first few days, which would be expected to inhibit growth of TBA-degrading microbes. Initial inhibition was also implied for the MTBE-baited bio-trap, but at lower concentrations and for a shorter time. After a few days, concentrations in groundwater flowing through the bio-traps dropped below inhibitory concentrations but remained 4–5 orders of magnitude higher than TBA or MTBE concentrations within the aquifer at the experimental site. Desorption from the bio-beads during ex situ deployment occurred at first as predicted by prior sorption analyses of bio-beads but with apparent hysteresis thereafter, possibly due to mass transfer limitations caused by colonizing microbes. These results suggest that TBA- or MTBE-baited bio-traps could be baited at lower initial total mass loading with no detriment to trapping ability. The bio-traps were able to collect detectable amounts of microbial DNA and thus allow some insight into the sparse microbial community present in the aquifer during remediation of the low concentration plume.
MTBE; TBA; Bio-trap; In situ microcosm; Biodegradation; Stable isotope probing
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.
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.
There have been many studies that utilize the bio-impedance measurement method to analyze the movements of the upper and lower limbs. A fixed electrical current flows into the limbs through four standard disposable electrodes in this method. The current flows in the muscles and blood vessels, which have relatively low resistivity levels in the human body. This method is used to measure bio-impedance changes following volume changes of muscles and blood vessels around a knee joint. The result of the bio-impedance changes is used to evaluate the movements. However, the method using the standard disposable electrodes has a restriction related to its low bio-impedance changes: the standard disposable electrodes are only able to measure bio-impedance from a limited part of a muscle. Moreover, it is impossible to use continuously, as the electrodes are designed to be disposable. This paper describes a conductive fabric sensor (CFS) using a bio-impedance measurement method and determines the optimum configuration of the sensor for estimating knee joint movements.
The upper side of subjects' lower limbs was divided into two areas and the lower side of subjects' lower limbs was divided into three areas. The spots were matched and 6 pairs were selected. Subjects were composed of 15 males (age: 30.7 ± 5.3, weight: 69.8 ± 4.2 kg, and height: 173.5 ± 2.8 cm) with no known problems with their knee joints. Bio-impedance changes according to knee joint flexion/extension assessments were calculated and compared with bio-impedance changes by an ankle joint flexion/extension test (SNR I) and a hip joint flexion/extension test (SNR II).
The bio-impedance changes of the knee joint flexion/extension assessment were 35.4 ± 20.0 Ω on the (1, 5) pair. SNR I was 3.8 ± 8.4 and SNR II was 6.6 ± 7.9 on the (1, 5) pair.
The optimum conductive fabric sensor configuration for evaluating knee joint movements were represented by the (1, 5) pair.
The HL7 SGML/XML Special Interest Group is developing the HL7 Document Patient Record Architecture. This draft proposal strives to create a common data architecture for the interoperability of healthcare documents. Key components are that it is under the umbrella of HL7 standards, it is specified in Extensible Markup Language, the semantics are drawn from the HL7 Reference Information Model, and the document specifications form an architecture that, in aggregate, define the semantics and structural constraints necessary for the exchange of clinical documents. The proposal is a work in progress and has not yet been submitted to HL7's formal balloting process.
Data summarization and triage is one of the current top challenges in visual analytics. The goal is to let users visually inspect large data sets and examine or request data with particular characteristics. The need for summarization and visual analytics is also felt when dealing with digital representations of DNA sequences. Genomic data sets are growing rapidly, making their analysis increasingly more difficult, and raising the need for new, scalable tools. For example, being able to look at very large DNA sequences while immediately identifying potentially interesting regions would provide the biologist with a flexible exploratory and analytical tool. In this paper we present a new concept, the “information profile”, which provides a quantitative measure of the local complexity of a DNA sequence, independently of the direction of processing. The computation of the information profiles is computationally tractable: we show that it can be done in time proportional to the length of the sequence. We also describe a tool to compute the information profiles of a given DNA sequence, and use the genome of the fission yeast Schizosaccharomyces pombe strain 972 h− and five human chromosomes 22 for illustration. We show that information profiles are useful for detecting large-scale genomic regularities by visual inspection. Several discovery strategies are possible, including the standalone analysis of single sequences, the comparative analysis of sequences from individuals from the same species, and the comparative analysis of sequences from different organisms. The comparison scale can be varied, allowing the users to zoom-in on specific details, or obtain a broad overview of a long segment. Software applications have been made available for non-commercial use at http://bioinformatics.ua.pt/software/dna-at-glance.
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
Bio-responsive polymer architectures can empower medical therapies by engaging molecular feedback-response mechanisms resembling the homeostatic adaptation of living tissues to varying environmental constraints. Here we show that a blood coagulation-responsive hydrogel system can deliver heparin in amounts triggered by the environmental levels of thrombin, the key enzyme of the coagulation cascade, which—in turn—becomes inactivated due to released heparin. The bio-responsive hydrogel quantitatively quenches blood coagulation over several hours in the presence of pro-coagulant stimuli and during repeated incubation with fresh, non-anticoagulated blood. These features enable the introduced material to provide sustainable, autoregulated anticoagulation, addressing a key challenge of many medical therapies. Beyond that, the explored concept may facilitate the development of materials that allow the effective and controlled application of drugs and biomolecules.
Implementing biomolecular recognition mechanisms in synthetic materials may enable a wealth of biomedical and related applications. Here Maitz et al. present a bio-responsive hydrogel that releases the anticoagulant heparin in amounts proportional to the environmental levels of the procoagulatory protein thrombin.
A new protein immobilization and purification system has been developed based on the use of polyhydroxyalkanoates (PHAs, or bioplastics), which are biodegradable polymers accumulated as reserve granules in the cytoplasm of certain bacteria. The N-terminal domain of the PhaF phasin (a PHA-granule-associated protein) from Pseudomonas putida GPo1 was used as a polypeptide tag (BioF) to anchor fusion proteins to PHAs. This tag provides a novel way to immobilize proteins in vivo by using bioplastics as supports. The granules carrying the BioF fusion proteins can be isolated by a simple centrifugation step and used directly for some applications. Moreover, when required, a practically pure preparation of the soluble BioF fusion protein can be obtained by a mild detergent treatment of the granule. The efficiency of this system has been demonstrated by constructing two BioF fusion products, including a functional BioF-β-galactosidase. This is the first example of an active bioplastic consisting of a biodegradable matrix carrying an active enzyme.
Motivation: High-throughput technologies provide fundamental informations concerning thousands of genes. Many of the current research laboratories daily use one or more of these technologies and end-up with lists of genes. Assessing the originality of the results obtained includes being aware of the number of publications available concerning individual or multiple genes and accessing information about these publications. Faced with the exponential growth of publications avaliable and number of genes involved in a study, this task is becoming particularly difficult to achieve.
Results: We introduce GeneValorization, a web-based tool that gives a clear and handful overview of the bibliography available corresponding to the user input formed by (i) a gene list (expressed by gene names or ids from EntrezGene) and (ii) a context of study (expressed by keywords). From this input, GeneValorization provides a matrix containing the number of publications with co-occurrences of gene names and keywords. Graphics are automatically generated to assess the relative importance of genes within various contexts. Links to publications and other databases offering information on genes and keywords are also available. To illustrate how helpful GeneValorization is, we will consider the gene list of the OncotypeDX prognostic marker test.
Supplementary information: Supplementary data are available at Bioinformatics online.
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.
On the 4th of July, 2005, the Saline Systems editorial group launched the new online open access journal, Saline Systems, with BioMed Central as the publisher. The scope of the journal includes both basic and applied research on halophilic organisms and saline environments, from gene systems to ecosystems. The stated goal of the journal is to meet publication needs for researchers working in coastal and inland saline environments and provide an interdisciplinary and readily accessible forum for scientists worldwide. The inaugural volume of the journal contains a significant number of high quality original research papers and reviews on a wide range of relevant topics. At the end of the launch period, from January 1, 2006 onwards, the journal will be introducing article-processing charges to cover the cost of publication. Charges will be partly or completely waived for authors from BioMed Central institutional subscribers and in cases of financial hardship.
Considering that 80 genomes have been sequenced, providing us with the static information of the genome, it is still a long way to reveal the relationship between complex genotypes and phenotypes. The transcriptional regulation process is one of the obstacles that need to be understood to bridge our current information gap. It describes the first step from the genomic sequence information to RNA templates used for protein production or as direct functional units, like non-coding RNAs (e.g. micro RNAs). This introduction aims to highlight the key aspects of the transcriptional process from our current understanding.
Although mutation analysis serves as a key part in making a definitive diagnosis about a genetic disease, it still remains a time-consuming step to interpret their biological implications through integration of various lines of archived information about genes in question. To expedite this evaluation step of disease-causing genetic variations, here we developed Mutation@A Glance (http://rapid.rcai.riken.jp/mutation/), a highly integrated web-based analysis tool for analysing human disease mutations; it implements a user-friendly graphical interface to visualize about 40 000 known disease-associated mutations and genetic polymorphisms from more than 2600 protein-coding human disease-causing genes. Mutation@A Glance locates already known genetic variation data individually on the nucleotide and the amino acid sequences and makes it possible to cross-reference them with tertiary and/or quaternary protein structures and various functional features associated with specific amino acid residues in the proteins. We showed that the disease-associated missense mutations had a stronger tendency to reside in positions relevant to the structure/function of proteins than neutral genetic variations. From a practical viewpoint, Mutation@A Glance could certainly function as a ‘one-stop’ analysis platform for newly determined DNA sequences, which enables us to readily identify and evaluate new genetic variations by integrating multiple lines of information about the disease-causing candidate genes.
genetic disease; mutation; polymorphism; bioinformatics; protein structure
We present a soft bio-machine constructed from biological motors (actin/myosin). We have found that chemically cross-linked polymer-actin complex gel filaments can move on myosin coated surfaces with a velocity as high as that of native F-actin, by coupling to ATP hydrolysis. Additionally, it is shown that the velocity of polymer-actin complex gel depends on the species of polycations binding to the F-actins. Since the design of functional actuators of well-defined size and morphology is important, the structural behavior of polymer-actin complexes has been investigated. Our results show that the morphology and growth size of polymer-actin complex can be controlled by changes in the electrostatic interactions between F-actins and polycations. Our results indicate that bio actuators with desired shapes can be created by using a polymer-actin complex.
Biological motors; self-assembly; hierarchical structure; soft-bio-machine
Chemically modified nucleic acids (CNAs) are widely explored as antisense oligonucleotide or small interfering RNA (siRNA) candidates for therapeutic applications. CNAs are also of interest in diagnostics, high-throughput genomics and target validation, nanotechnology and as model systems in investigations directed at a better understanding of the etiology of nucleic acid structure as well as the physical-chemical and pairing properties of DNA and RNA and for probing protein-nucleic acid interactions. In this article we review research conducted by our laboratory over the past two decades with a focus on crystal structure analyses of CNAs and artificial pairing systems. We highlight key insights into issues ranging from conformational distortions as a consequence of modification to the modulation of pairing strength and RNA affinity by stereoelectronic effects and hydration. Although crystal structures have only been determined for a subset of the large number of modifications that were synthesized and analyzed in the oligonucleotide context to date, they have yielded guiding principles for the design of new analogs with tailormade properties, including pairing specificity, nuclease resistance and cellular uptake. And, perhaps less obviously, crystallographic studies of CNAs and synthetic pairing systems have shed light on fundamental aspects of DNA and RNA structure and function that would not have been disclosed by investigations solely focused on the natural nucleic acids.