This study describes a unique function of taurocholate in bile canalicular formation involving signaling through a cAMP-Epac-MEK-Rap1-LKB1-AMPK pathway. In rat hepatocyte sandwich cultures, polarization was manifested by sequential progression of bile canaliculi from small structures to a fully branched network. Taurocholate accelerated canalicular network formation and concomitantly increased cAMP, which were prevented by adenyl cyclase inhibitor. The cAMP-dependent PKA inhibitor did not prevent the taurocholate effect. In contrast, activation of Epac, another cAMP downstream kinase, accelerated canalicular network formation similar to the effect of taurocholate. Inhibition of Epac downstream targets, Rap1 and MEK, blocked the taurocholate effect. Taurocholate rapidly activated MEK, LKB1, and AMPK, which were prevented by inhibition of adenyl cyclase or MEK. Our previous study showed that activated-LKB1 and AMPK participate in canalicular network formation. Linkage between bile acid synthesis, hepatocyte polarization, and regulation of energy metabolism is likely important in normal hepatocyte development and disease.

While building information modeling (BIM) is widely embraced by the architectural, engineering and construction (AEC) industry, BIM adoption in facilities management (FM) is still relatively new and limited. BIM deliverables from design and construction generally do not fulfill FM needs unless they are clearly specified and carefully managed.

The Facilities Group responsible for the Janelia Research Campus of the Howard Hughes Medical Institute (HHMI) expects any BIM platform to provide value in operations and maintenance. Janelia’s BIM vision goes beyond transferring BIM data to computerized maintenance management software (CMMS) and integrated workplace management system (IWMS) platforms. Instead, Janelia creates and maintains FM-capable BIM, utilizes the models to solve operational challenges and improves safety and efficiency in various ways, including engineering analysis for heating, ventilation and air conditioning (HVAC), electrical and plumbing; building automation systems (BAS) analysis; operational impact analysis; and BIM-aided operation safety.

Myosin VI is the only minus-end actin motor and is coupled to various cellular processes ranging from endocytosis to transcription. This multi-potent nature is achieved through alternative isoform splicing and interactions with a network of binding partners. There is a complex interplay between isoforms and binding partners to regulate myosin VI. Here, we have compared the regulation of two myosin VI splice isoforms by two different binding partners. By combining biochemical and single-molecule approaches, we propose that myosin VI regulation follows a generic mechanism, independently of the spliced isoform and the binding partner involved. We describe how myosin VI adopts an autoinhibited backfolded state which is released by binding partners. This unfolding activates the motor, enhances actin binding and can subsequently trigger dimerization. We have further expanded our study by using single molecule imaging to investigate the impact of binding partners upon myosin VI molecular organisation and dynamics.

In the primate primary visual area (V1), the ocular dominance pattern consists of alternating monocular stripes. Stripe orientation follows systematic trends preserved across several species. I propose that these trends result from minimizing the length of intra-cortical wiring needed to recombine information from the two eyes in order to achieve the perception of depth. I argue that the stripe orientation at any point of V1 should follow the direction of binocular disparity in the corresponding point of the visual field. The optimal pattern of stripes determined from this argument agrees with the ocular dominance pattern of macaque and Cebus monkeys. This theory predicts that for any point in the visual field the limits of depth perception are greatest in the direction along the ocular dominance stripes at that point.

Quantitative phase imaging (QPI) has proven to be a valuable tool for advanced biological and pharmacological research, providing phase information for the study of cell features and physiology in label-free conditions. The next step for QPI to become a gold standard is the quantitative assessment of the phase gradients over the different microscopy setups. Given the large variety of QPI systems, a systematic comparison is a challenging task, and requires a calibration target representative of the living samples. In this paper, we introduce a tailor-made 3D-printed phantom derived from phase images of eukaryotic cells. It comprises typical morphologies and optical thicknesses found in biological cultures and is characterized with digital holographic microscopy (reference measurements). The performance of three different full field QPI optical systems, in terms of optical path difference and dry mass accuracy, were evaluated. This phantom opens up other possibilities for the validation of reconstruction algorithms and post-processing routines, and paves the way for calibration targets designed ad hoc for specific biological questions.

Aldolases are enzymes with potential applications in biosynthesis, depending on their activity, specificity and stability. In the present study, the genomes of Sulfolobus species were screened for aldolases. Two new KDGA [2-keto-3-deoxygluconate (2-oxo-3-deoxygluconate) aldolases] from Sulfolobus acidocaldarius and Sulfolobus tokodaii were identified, overexpressed in Escherichia coli and characterized. Both enzymes were found to have biochemical properties similar to the previously characterized S. solfataricus KDGA, including the condensation of pyruvate and either D,L-glyceraldehyde or D,L-glyceraldehyde 3-phosphate. The crystal structure of S. acidocaldarius KDGA revealed the presence of a novel phosphate-binding motif that allows the formation of multiple hydrogen-bonding interactions with the acceptor substrate, and enables high activity with glyceraldehyde 3-phosphate. Activity analyses with unnatural substrates revealed that these three KDGAs readily accept aldehydes with two to four carbon atoms, and that even aldoses with five carbon atoms are accepted to some extent. Water-mediated interactions permit binding of substrates in multiple conformations in the spacious hydrophilic binding site, and correlate with the observed broad substrate specificity.

Modern biological research relies heavily on microscopic imaging. The advanced genetic toolkit of Drosophila makes it possible to label molecular and cellular components with unprecedented level of specificity necessitating the application of the most sophisticated imaging technologies. Imaging in Drosophila spans all scales from single molecules to the entire populations of adult organisms, from electron microscopy to live imaging of developmental processes. As the imaging approaches become more complex and ambitious, there is an increasing need for quantitative, computer-mediated image processing and analysis to make sense of the imagery. Bioimage Informatics is an emerging research field that covers all aspects of biological image analysis from data handling, through processing, to quantitative measurements, analysis and data presentation. Some of the most advanced, large scale projects, combining cutting edge imaging with complex bioimage informatics pipelines, are realized in the Drosophila research community. In this review, we discuss the current research in biological image analysis specifically relevant to the type of systems level image datasets that are uniquely available for the Drosophila model system. We focus on how state-of-the-art computer vision algorithms are impacting the ability of Drosophila researchers to analyze biological systems in space and time. We pay particular attention to how these algorithmic advances from computer science are made usable to practicing biologists through open source platforms and how biologists can themselves participate in their further development.

In recent years, the deluge of complicated molecular and cellular microscopic images creates compelling challenges for the image computing community. There has been an increasing focus on developing novel image processing, data mining, database and visualization techniques to extract, compare, search and manage the biological knowledge in these data-intensive problems. This emerging new area of bioinformatics can be called ’bioimage informatics’. This article reviews the advances of this field from several aspects, including applications, key techniques, available tools and resources. Application examples such as high-throughput/high-content phenotyping and atlas building for model organisms demonstrate the importance of bioimage informatics. The essential techniques to the success of these applications, such as bioimage feature identification, segmentation and tracking, registration, annotation, mining, image data management and visualization, are further summarized, along with a brief overview of the available bioimage databases, analysis tools and other resources.