Expertise In Biology Research Articles

Benson Earl Ginsburg (1918–2016): a pioneer in behavior genetics

Benson Earl Ginsburg (1918–2016): a pioneer in behavior genetics

Meeting Report From the Prostate Cancer Foundation Scientific Working Group on Radium-223.

The Prostate Cancer Foundation (PCF) convened a Scientific Working Group Meeting on Radium-223 on September 8, 2016, at The Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center. The meeting was attended by 18 investigators with expertise in radium-223, bone biology, molecular imaging, biomarkers, and prostate cancer clinical trials. The goal of this meeting was to discuss the known and unknown surroundings the therapeutic effects of the bone targeting agent radium-223, in bone metastatic prostate cancer therapy, and to outline the most critical studies needed to improve the clinical use of this agent. Three major topic areas were discussed: (1) the basic science of radium; (2) immuno-adjuvant properties of radium therapy; and (3) high impact clinical trials and correlative science. This article reviews the major topics discussed at the meeting for the purpose of accelerating studies that will improve the use of radium-223 in the treatment of prostate cancer patients. Prostate 77:245-254, 2017. © 2016 Wiley Periodicals, Inc.

The Eighth Central European Conference “Chemistry towards Biology”: Snapshot

The Eighth Central European Conference “Chemistry towards Biology” was held in Brno, Czech Republic, on August 28–September 1, 2016 to bring together experts in biology, chemistry and design of bioactive compounds; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topics of the conference covered “Chemistry towards Biology”, meaning that the event welcomed chemists working on biology-related problems, biologists using chemical methods, and students and other researchers of the respective areas that fall within the common scope of chemistry and biology. The authors of this manuscript are plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.

Region Growing for Segmenting Green Microalgae Images.

We describe a specialized methodology for segmenting 2D microscopy digital images of freshwater green microalgae. The goal is to obtain representative algae shapes to extract morphological features to be employed in a posterior step of taxonomical classification of the species. The proposed methodology relies on the seeded region growing principle and on a fine-tuned filtering preprocessing stage to smooth the input image. A contrast enhancement process then takes place to highlight algae regions on a binary pre-segmentation image. This binary image is also employed to determine where to place the seed points and to estimate the statistical probability distributions that characterize the target regions, i.e., the algae areas and the background, respectively. These preliminary stages produce the required information to set the homogeneity criterion for region growing. We evaluate the proposed methodology by comparing its resulting segmentations with a set of corresponding ground-truth segmentations (provided by an expert biologist) and also with segmentations obtained with existing strategies. The experimental results show that our solution achieves highly accurate segmentation rates with greater efficiency, as compared with the performance of standard segmentation approaches and with an alternative previous solution, based on level-sets, also specialized to handle this particular problem.

One Health: parasites and beyond

The field of parasitism is broad, encompassing relationships between organisms where one benefits at the expense of another. Traditionally the discipline focuses on eukaryotes, with the study of bacteria and viruses complementary but distinct. Nonetheless, parasites vary in size and complexity from single celled protozoa, to enormous plants like those in the genus Rafflesia. Lifecycles range from obligate intracellular to extensive exoparasitism. Examples of parasites include high-profile medical and zoonotic pathogens such as Plasmodium, veterinary pathogens of wild and captive animals and many of the agents which cause neglected tropical diseases, stretching to parasites which infect plants and other parasites (e.g. Kikuchi et al. 2011; Hotez et al. 2014; Blake et al. 2015; Hemingway, 2015; Meekums et al. 2015; Sandlund et al. 2015). The breadth of parasitology has been matched by the variety of ways in which parasites are studied, drawing upon biological, chemical, molecular, epidemiological and other expertise. Despite such breadth bridging between disciplines has commonly been problematic, regardless of extensive encouragement from government agencies, peer audiences and funding bodies promoting multidisciplinary research. Now, progress in understanding and collaboration can benefit from establishment of the One Health concept (Zinsstag et al. 2012; Stark et al. 2015). One Health draws upon biological, environmental, medical, veterinary and social science disciplines in order to improve human, animal and environmental health, although it remains tantalizingly difficult to engage many relevant parties. For infectious diseases traditional divides have been exacerbated as the importance of wildlife reservoirs, climate change, food production systems and socio-economic diversity have been recognized but often not addressed in a multidisciplinary manner. In response the 2015 Autumn Symposium organized by the British Society for Parasitology (BSP; https://www.bsp.uk.net/home/) was focused on One Health, running under the title 'One Health: parasites and beyond…'. The meeting, held at the Royal Veterinary College (RVC) in Camden, London from September 14th to 15th, drew upon a blend of specialist parasitology reinforced with additional complementary expertise. Scientists, advocates, policy makers and industry representatives were invited to present at the meeting, promoting and developing One Health understanding with relevance to parasitology. The decision to widen the scope of the meeting to non-parasitological, but informative topics, is reflected in the diversity of the articles included in this special issue. A key feature of the meeting was encouragement of early career scientists, with more than 35% of the delegates registered as students and 25 posters.

Cost and feasibility of a barrier to halt the spread of invasive cane toads in arid Australia: incorporating expert knowledge into model‐based decision‐making

Summary Active engagement with practitioners is a crucial component of model‐based decision‐making in conservation management; it can assist with data acquisition, improve models and help narrow the ‘knowing–doing’ gap. We worked with practitioners of one of the worst invasive species in Australia, the cane toad Rhinella marina, to revise a model that estimates the effectiveness of landscape barriers to contain spread. The original model predicted that the invasion could be contained by managing artificial watering points on pastoral properties, but was initially met with scepticism by practitioners, in part due to a lack of engagement during model development. We held a workshop with practitioners and experts in cane toad biology. Using structured decision‐making, we elicited concerns about the original model, revised its structure, updated relevant input data, added an economic component and found the most cost‐effective location for a barrier across a range of fixed budgets and management scenarios. We then conducted scenario analyses to test the sensitivity of management decisions to model revisions. We found that toad spread could be contained for all of the scenarios tested. Our modelling suggests a barrier could cost $4·5 M (2015 AUD) over 50 years for the most likely landscape scenario. The incorporation of practitioner knowledge into the model was crucial. As well as improving engagement, when we incorporated practitioner concerns (particularly regarding the effects of irrigation and dwellings on toad spread), we found a different location for the optimal barrier compared to a previously published study (Tingley et al. 2013). Synthesis and applications. Through engagement with practitioners, we turned an academic modelling exercise into a decision‐support tool that integrated local information, and considered more realistic scenarios and constraints. Active engagement with practitioners led to productive revisions of a model that estimates the effectiveness of a landscape barrier to contain spread of the invasive cane toad R. marina. Benefits also include greater confidence in model predictions, improving our assessment of the cost and feasibility of containing the spread of toads.

Semi-automated image analysis of gel electrophoresis of cerebrospinal fluid for oligoclonal band detection.

Detection of oligoclonal electrophoretic bands in cerebrospinal fluid (CSF) is an important diagnostic tool for Multiple Sclerosis (MS). Electrophoretic profiles are difficult to interpret due to low contrast and artefacts. A semi-automated method to ease analysis and to reduce subjectivity is presented. The method sequentially converts color images to grayscale, realigns bands, removes artifacts, then converts 2D images to a signal, before detecting, thresholding and editing peaks to optimize profiles. Such treated profiles (21 positive and 15 negative) are compared to ground truth analysis of an expert biologist. 16 profiles over 21 are well detected positive and 12 profiles over 15 are detected negative, results seem similar to inter-experts variability reported in literature.

Modelling with ANIMO: between fuzzy logic and differential equations.

BackgroundComputational support is essential in order to reason on the dynamics of biological systems. We have developed the software tool ANIMO (Analysis of Networks with Interactive MOdeling) to provide such computational support and allow insight into the complex networks of signaling events occurring in living cells. ANIMO makes use of timed automata as an underlying model, thereby enabling analysis techniques from computer science like model checking. Biology experts are able to use ANIMO via a user interface specifically tailored for biological applications. In this paper we compare the use of ANIMO with some established formalisms on two case studies.ResultsANIMO is a powerful and user-friendly tool that can compete with existing continuous and discrete paradigms. We show this by presenting ANIMO models for two case studies: Drosophila melanogaster circadian clock, and signal transduction events downstream of TNF α and EGF in HT-29 human colon carcinoma cells. The models were originally developed with ODEs and fuzzy logic, respectively.ConclusionsTwo biological case studies that have been modeled with respectively ODE and fuzzy logic models can be conveniently modeled using ANIMO. The ANIMO models require less parameters than ODEs and are more precise than fuzzy logic. For this reason we position the modelling paradigm of ANIMO between ODEs and fuzzy logic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0286-z) contains supplementary material, which is available to authorized users.

Leveraging a relationship with biology to expand a relationship with physics

Biology student's shifts in identity, affect, and epistemology in a physics course which leverages students' identity and expertise in biology to promote a stronger relationship with physics.

Pediatric high-grade glioma: biologically and clinically in need of new thinking.

High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management.

Proceedings of the International Summit on Human Gene Editing: a global discussion-Washington, D.C., December 1-3, 2015.

The US Academies of Sciences and Medicine, the Royal Society, and the Chinese Academy of Sciences convened a summit of experts in biology, medicine, law, ethics, sociology, and journalism, in December 2015 to review the state of the art in gene editing technology and discuss the medical and social ramifications of the technologies. The summit concluded with the following consensus recommendations: (1) intensive basic and preclinical research in animal and human models should proceed with appropriate legal and ethical oversight; (2) clinical applications in somatic cells must be rigorously evaluated within existing and evolving regulatory frameworks for gene therapy; (3) it would be irresponsible to proceed with any clinical use of germline editing until relevant safety and efficacy issues have been resolved and there is broad societal consensus about such a use; and (4) the international community should strive to establish generally acceptable uses of human germline editing.

Evaluating Viewpoint Entropy for Ribbon Representation of Protein Structure

AbstractWhile many measures of viewpoint goodness have been proposed in computer graphics, none have been evaluated for ribbon representations of protein secondary structure. To fill this gap, we conducted a user study on Amazon's Mechanical Turk platform, collecting human viewpoint preferences from 65 participants for 4 representative superfamilies of protein domains. In particular, we evaluated viewpoint entropy, which was previously shown to be a good predictor for human viewpoint preference of other, mostly non‐abstract objects. In a second study, we asked 7 experts in molecular biology to find the best viewpoint of the same protein domains and compared their choices with viewpoint entropy.Our results indicate that viewpoint entropy overall is a significant predictor of human viewpoint preference for ribbon representations of protein secondary structure. However, the accuracy depends on the type and composition of the structure: while most participants agree on good viewpoints for structures with mainly beta sheets, viewpoint preference varies considerably for complex arrangements of alpha helices. Finally, experts tend to choose viewpoints of both low and high viewpoint entropy to emphasize different aspects of the respective structure.

Exploring the MACH Model's Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms.

When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of the model in an undergraduate biology classroom as an educational tool to address some of the known challenges. To find out how well students' written explanations represent components of the MACH model before and after they were taught about it and why students think the MACH model was useful, we conducted an exploratory multiple case study with four interview participants. We characterize how two students explained biological mechanisms before and after a teaching intervention that used the MACH components. Inductive analysis of written explanations and interviews showed that MACH acted as an effective metacognitive tool for all four students by helping them to monitor their understanding, communicate explanations, and identify explanatory gaps. Further research, though, is needed to more fully substantiate the general usefulness of MACH for promoting students' metacognition about their understanding of biological mechanisms.

Badapple: promiscuity patterns from noisy evidence.

BackgroundBioassay data analysis continues to be an essential, routine, yet challenging task in modern drug discovery and chemical biology research. The challenge is to infer reliable knowledge from big and noisy data. Some aspects of this problem are general with solutions informed by existing and emerging data science best practices. Some aspects are domain specific, and rely on expertise in bioassay methodology and chemical biology. Testing compounds for biological activity requires complex and innovative methodology, producing results varying widely in accuracy, precision, and information content. Hit selection criteria involve optimizing such that the overall probability of success in a project is maximized, and resource-wasteful “false trails” are avoided. This “fail-early” approach is embraced both in pharmaceutical and academic drug discovery, since follow-up capacity is resource-limited. Thus, early identification of likely promiscuous compounds has practical value.ResultsHere we describe an algorithm for identifying likely promiscuous compounds via associated scaffolds which combines general and domain-specific features to assist and accelerate drug discovery informatics, called Badapple: bioassay-data associative promiscuity pattern learning engine. Results are described from an analysis using data from MLP assays via the BioAssay Research Database (BARD) http://bard.nih.gov. Specific examples are analyzed in the context of medicinal chemistry, to illustrate associations with mechanisms of promiscuity. Badapple has been developed at UNM, released and deployed for public use two ways: (1) BARD plugin, integrated into the public BARD REST API and BARD web client; and (2) public web app hosted at UNM.ConclusionsBadapple is a method for rapidly identifying likely promiscuous compounds via associated scaffolds. Badapple generates a score associated with a pragmatic, empirical definition of promiscuity, with the overall goal to identify “false trails” and streamline workflows. Unlike methods reliant on expert curation of chemical substructure patterns, Badapple is fully evidence-driven, automated, self-improving via integration of additional data, and focused on scaffolds. Badapple is robust with respect to noise and errors, and skeptical of scanty evidence.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-016-0137-3) contains supplementary material, which is available to authorized users.

The cellular microscopy phenotype ontology.

BackgroundPhenotypic data derived from high content screening is currently annotated using free-text, thus preventing the integration of independent datasets, including those generated in different biological domains, such as cell lines, mouse and human tissues.DescriptionWe present the Cellular Microscopy Phenotype Ontology (CMPO), a species neutral ontology for describing phenotypic observations relating to the whole cell, cellular components, cellular processes and cell populations. CMPO is compatible with related ontology efforts, allowing for future cross-species integration of phenotypic data. CMPO was developed following a curator-driven approach where phenotype data were annotated by expert biologists following the Entity-Quality (EQ) pattern. These EQs were subsequently transformed into new CMPO terms following an established post composition process.ConclusionCMPO is currently being utilized to annotate phenotypes associated with high content screening datasets stored in several image repositories including the Image Data Repository (IDR), MitoSys project database and the Cellular Phenotype Database to facilitate data browsing and discoverability.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

Contribution of polymeric materials to progress in xenotransplantation of microencapsulated cells: a review.

Cell microencapsulation and subsequent transplantation of the microencapsulated cells require multidisciplinary approaches. Physical, chemical, biological, engineering, and medical expertise has to be combined. Several natural and synthetic polymeric materials and different technologies have been reported for the preparation of hydrogels, which are suitable to protect cells by microencapsulation. However, owing to the frequent lack of adequate characterization of the hydrogels and their components as well as incomplete description of the technology, many results of in vitro and in vivo studies appear contradictory or cannot reliably be reproduced. This review addresses the state of the art in cell microencapsulation with special focus on microencapsulated cells intended for xenotransplantation cell therapies. The choice of materials, the design and fabrication of the microspheres, as well as the conditions to be met during the cell microencapsulation process, are summarized and discussed prior to presenting research results of in vitro and in vivo studies. Overall, this review will serve to sensitize medically educated specialists for materials and technological aspects of cell microencapsulation.

Research Needs for Understanding the Biology of Overdiagnosis in Cancer Screening.

Many cancers offer an extended window of opportunity for early detection and therapeutic intervention that could lead to a reduction in cause-specific mortality. The pursuit of early detection in screening settings has resulted in decreased incidence and mortality for some cancers (e.g., colon and cervical cancers), and increased incidence with only modest or no effect on cause-specific mortality in others (e.g., breast and prostate). Whereas highly sensitive screening technologies are better at detecting a number of suspected "cancers" that are indolent and likely to remain clinically unimportant in the lifetime of a patient, defined as overdiagnosis, they often miss cancers that are aggressive and tend to present clinically between screenings, known as interval cancers. Unrecognized overdiagnosis leads to overtreatment with its attendant (often long-lasting) side effects, anxiety, and substantial financial harm. Existing methods often cannot differentiate indolent lesions from aggressive ones or understand the dynamics of neoplastic progression. To correctly identify the population that would benefit the most from screening and identify the lesions that would benefit most from treatment, the evolving genomic and molecular profiles of individual cancers during the clinical course of progression or indolence must be investigated, while taking into account an individual's genetic susceptibility, clinical and environmental risk factors, and the tumor microenvironment. Practical challenges lie not only in the lack of access to tissue specimens that are appropriate for the study of natural history, but also in the absence of targeted research strategies. This commentary summarizes the recommendations from a diverse group of scientists with expertise in basic biology, translational research, clinical research, statistics, and epidemiology and public health professionals convened to discuss research directions. J. Cell. Physiol. 231: 1870-1875, 2016. © 2015 Wiley Periodicals, Inc.

Translating the Science of Aging into Therapeutic Interventions.

Life and health span have been extended in experimental animals using drugs that are potentially translatable into humans. Considerable effort is needed beyond the usual steps in drug development to devise the models, and realistic preclinical and clinical trial strategies are required to advance these agents into clinical application. It will be important to focus on subjects who already have symptoms or are at imminent risk of developing disorders related to fundamental aging processes, to use short-term, clinically relevant outcomes, as opposed to long-term outcomes, such as health span or life span, and to validate endpoint measures so they are acceptable to regulatory agencies. Funding is a roadblock, as is shortage of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and investigational new drug clinical trials. Strategies for developing a path from the bench to the bedside are reviewed for interventions that target fundamental aging mechanisms.

THE DEVELOPMENT OF BIOLOGY MATERIAL RESOURCES BY METACOGNITIVE STRATEGY

The Development of Biology Material Resources by Metacognitive Strategy The study was aimed at finding out the suitability of Biology Materials using the metacognitive strategy. The materials were textbooks, self-understanding Evaluation Sheet and the key, lesson plan, and tests including the answer key. The criteria of appropriateness included the relevance of the resources with the content validity, face va­lidity and the language. This research and development study was carried out employing a 3D model, namely define, design and develop. At the define stage, three topics were selected for analysis, they were virus, Endocrine System, and Genetic material. During the design phase, the physical appearance of the materials was suited with the Metacognitive Strategy. At the develop phase, the material resources were examined and validated by two Biology experts and senior teachers of Biology. The results showed that the Biology material Resources using Metacognitive Strategy developed in the study has fell into the category of very good ( score > 3.31) and was therefore considered suitable.