Perceived Disgust and Personal Experiences are Associated with Acceptance of Dissections in Schools

ERIC Educational Resources Information Center

Fancovicova, Jana; Prokop, Pavol; Leskova, Andrea

2013-01-01

Animal dissections are essential parts of anatomy/zoology courses, but their effectiveness is influenced by student attitudes and emotions. Here we examined attitudes toward dissections in 397 prospective biology teachers enrolling two Slovak universities. Perceived disgust of dissections negatively correlated with other attitudes toward…

Rapid, Optimized Interactomic Screening

PubMed Central

Hakhverdyan, Zhanna; Domanski, Michal; Hough, Loren; Oroskar, Asha A.; Oroskar, Anil R.; Keegan, Sarah; Dilworth, David J.; Molloy, Kelly R.; Sherman, Vadim; Aitchison, John D.; Fenyö, David; Chait, Brian T.; Jensen, Torben Heick; Rout, Michael P.; LaCava, John

2015-01-01

We must reliably map the interactomes of cellular macromolecular complexes in order to fully explore and understand biological systems. However, there are no methods to accurately predict how to capture a given macromolecular complex with its physiological binding partners. Here, we present a screen that comprehensively explores the parameters affecting the stability of interactions in affinity-captured complexes, enabling the discovery of physiological binding partners and the elucidation of their functional interactions in unparalleled detail. We have implemented this screen on several macromolecular complexes from a variety of organisms, revealing novel profiles even for well-studied proteins. Our approach is robust, economical and automatable, providing an inroad to the rigorous, systematic dissection of cellular interactomes. PMID:25938370

Justifying the Dissection of Animals in Biology Teaching.

ERIC Educational Resources Information Center

Wheeler, Anthony G.

1993-01-01

Presents the idea that several points should be considered in animal dissection: (1) ethics; (2) the animal's position; (3) the law; and (4) the actual benefits to society. Recommends that students be carefully prepared for animal dissection. Contains 21 references. (DDR)

Beyond Dissection: Innovative Tools for Biology Education.

ERIC Educational Resources Information Center

Larson, Sandra, Ed.

This catalog lists resources available for classroom use in teaching about anatomy and physiology which are alternatives to dissection. The entries are provided under three main categories: (1) Whole Animal Dissection/Vivisection; (2) Animal Organ or System Anatomy and Physiology; and (3) Other, including animal behavior, biotechnology,…

Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM.

PubMed

Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

2015-01-01

Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

Systems Pharmacology Dissecting Holistic Medicine for Treatment of Complex Diseases: An Example Using Cardiocerebrovascular Diseases Treated by TCM

PubMed Central

Wang, Yonghua; Zheng, Chunli; Huang, Chao; Li, Yan; Chen, Xuetong; Wu, Ziyin; Wang, Zhenzhong; Xiao, Wei; Zhang, Boli

2015-01-01

Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future. PMID:26101539

"Dissection" of a Hair Dryer

ERIC Educational Resources Information Center

Eisenstein, Stan; Simpson, Jeff

2008-01-01

The electrical design of the common hair dryer is based almost entirely on relatively simple principles learned in introductory physics classes. Just as biology students dissect a frog to see the principles of anatomy in action, physics students can "dissect" a hair dryer to see how principles of electricity are used in a real system. They can…

Science Laboratory Depth of Learning: Interactive Multimedia Simulation and Virtual Dissection Software

ERIC Educational Resources Information Center

Yuza, Steve C.

2010-01-01

The purpose of this study was to determine the effects of interactive multimedia simulations and virtual dissection software on depth of learning among students participating in biology and chemistry laboratory courses. By understanding more about how simulation and virtual dissection software changes depth of learning, educators will have the…

Systems Biology Approaches to Dissecting Plant Cell Wall Biosynthesis Genes in Poplus (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

ScienceCinema

Glass, N. Louise; Pennacchio, Len

2018-02-13

N. Louise Glass from the University of California, Berkeley, presents a talk titled "Systems Biology Approaches to Dissecting Plant Cell Wall Biosynthesis Genes in Poplus" at the JGI 7th Annual Users Meeting: Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

A Laboratory Manual for Stepwise Cerebral White Matter Fiber Dissection.

PubMed

Koutsarnakis, Christos; Liakos, Faidon; Kalyvas, Aristotelis V; Sakas, Damianos E; Stranjalis, George

2015-08-01

White matter fiber dissection is an important method in acquiring a thorough neuroanatomic knowledge for surgical practice. Previous studies have definitely improved our understanding of intrinsic brain anatomy and emphasized on the significance of this technique in modern neurosurgery. However, current literature lacks a complete and concentrated laboratory guide about the entire dissection procedure. Hence, our primary objective is to introduce a detailed laboratory manual for cerebral white matter dissection by highlighting consecutive dissection steps, and to stress important technical comments facilitating this complex procedure. Twenty adult, formalin-fixed cerebral hemispheres were included in the study. Ten specimens were dissected in the lateromedial and 10 in the mediolateral direction, respectively, using the fiber dissection technique and the microscope. Eleven and 8 consecutive and distinctive dissection steps are recommended for the lateromedial and mediolateral dissection procedures, respectively. Photographs highlighting various anatomic landmarks accompany every step. Technical recommendations, facilitating the dissection process, are also indicated. The fiber dissection technique, although complex and time consuming, offers a three-dimensional knowledge of intrinsic brain anatomy and architecture, thus improving both the quality of microneurosurgery and the patient's standard of care. The present anatomic study provides a thorough dissection manual to those who study brain anatomy using this technique. Copyright © 2015 Elsevier Inc. All rights reserved.

Complex genetic diseases: controversy over the Croesus code.

PubMed

Wright, A F; Hastie, N D

2001-01-01

The polarization of views on how best to exploit new information from the Human Genome Project for medicine reflects our ignorance of the genetic architecture underlying common diseases: are susceptibility alleles common or rare, neutral or deleterious, few or many? Single-nucleotide polymorphism (SNP) technology is almost in place to dissect such diseases and to create a personalized medicine, but success is critically dependent on the biology and "Nature to be commanded must be obeyed" (Francis Bacon, 1620, Novum Organum).

Teachers' and Learners' Inclinations towards Animal Organ Dissection and Its Use in Problem-Solving

ERIC Educational Resources Information Center

Kavai, Portia; de Villiers, Rian; Fraser, William

2017-01-01

In Life Sciences (biology) education, both nationally and internationally, the study of animal and organ morphology has traditionally involved dissection since the early 19th century. This study focused on the inclinations of teachers and learners towards animal organ dissection, and its use in problem-solving in Grade 11 Life Sciences education…

A comparison of retention of anatomical knowledge in an introductory college biology course: Traditional dissection vs. virtual dissection

NASA Astrophysics Data System (ADS)

Taeger, Kelli Rae

Dissection has always played a crucial role in biology and anatomy courses at all levels of education. However, in recent years, ethical concerns, as well as improved technology, have brought to the forefront the issue of whether virtual dissection is as effective or whether it is more effective than traditional dissection. Most prior research indicated the two methods produced equal results. However, none of those studies examined retention of information past the initial test of knowledge. Two groups of college students currently enrolled in an introductory level college biology course were given one hour to complete a frog dissection. One group performed a traditional frog dissection, making cuts in an actual preserved frog specimen with scalpels and scissors. The other group performed a virtual frog dissection, using "The Digital Frog 2" software. Immediately after the dissections were completed, each group was given an examination consisting of questions on actual specimens, pictures generated from the computer software, and illustrations that neither group had seen. Two weeks later, unannounced, the groups took the same exam in order to test retention. The traditional dissection group scored significantly higher on two of the three sections, as well as the total score on the initial exam. However, with the exception of specimen questions (on which the traditional group retained significantly more information), there was no significant difference in the retention from exam 1 to exam 2 between the two groups. These results, along with the majority of prior studies, show that the two methods produce, for the most part, the same end results. Therefore, the decision of which method to employ should be based on the goals and preferences of the instructor(s) and the department. If that department's goals include: Being at the forefront of new technology, increasing time management, increasing student: teacher ratio for economic reasons, and/or ethical issues, then the choice should be the use of computer software. If the goals include: Students gaining a 3-dimensional feel for the location and relationship of parts to one another, students being able to see various naturally occurring anomalies, and increased experience with manipulation of dissection tools, then the choice should be dissection of actual specimens. It is important to note, however, that regardless of which method is chosen, the effectiveness of that method is very much dependent on the skill and enthusiasm of the instructor.

Animal Rights Activism Threatens Dissection.

ERIC Educational Resources Information Center

Holden, Constance

1990-01-01

Discussed is the movement against the use of dissections in science laboratories. Examples of protests across the United States are included. Compared is the plight of using animals in a biology classroom and the demise of the teaching of evolution in some areas. (KR)

Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

PubMed

Maple, Jodi; Møller, Simon G

2007-10-01

Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

Antiviral Innate Immunity through the lens of Systems Biology

PubMed Central

Tripathi, Shashank; García-Sastre, Adolfo

2015-01-01

Cellular innate immunity poses the first hurdle against invading viruses in their attempt to establish infection. This antiviral response is manifested with the detection of viral components by the host cell, followed by transduction of antiviral signals, transcription and translation of antiviral effectors and leads to the establishment of an antiviral state. These events occur in a rather branched and interconnected sequence than a linear path. Traditionally, these processes were studied in the context of a single virus and a host component. However, with the advent of rapid and affordable OMICS technologies it has become feasible to address such questions on a global scale. In the discipline of Systems Biology’, extensive omics datasets are assimilated using computational tools and mathematical models to acquire deeper understanding of complex biological processes. In this review we have catalogued and discussed the application of Systems Biology approaches in dissecting the antiviral innate immune responses. PMID:26657882

High affinity ligands from in vitro selection: Complex targets

PubMed Central

Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry

1998-01-01

Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188

Cat dissection and human cadaver prosection versus sculpting human structures from clay: A comparison of alternate approaches to human anatomy laboratory education

NASA Astrophysics Data System (ADS)

Waters, John R.

Dissection and vivisection are traditional approaches to biology laboratory education. In the case of human anatomy teaching laboratories, there is a long tradition of using human and animal cadaver specimens in the classroom. In a review of the literature comparing traditional dissection and vivisection lessons to alternative lessons designed to reduce the time spent dissecting or the numbers of animals used, we conclude that it is difficult to come to any conclusion regarding the efficacy of different approaches. An analysis of the literature is confounded because many studies have very low statistical power or other methodological weaknesses, and investigators rely on a wide variety of testing instruments to measure an equally varied number of course objectives. Additional well designed studies are necessary before educators can reach any informed conclusions about the efficacy of traditional versus alternative approaches to laboratory education. In our experiments, we compared a traditional cat dissection based undergraduate human anatomy lesson to an alternative where students sculpted human muscles onto plastic human skeletons. Students in the alternative treatment performed significantly better than their peers in the traditional treatment when answering both lower and higher order human anatomy questions. In a subsequent experiment with a similar design, we concluded that the superior performance of the students in the alternative treatment on anatomy exams was likely due to the similarity between the human anatomy representation studied in lab, and the human anatomy questions asked on the exams. When the anatomy questions were presented in the context of a cat specimen, students in the traditional cat dissection treatment outperformed their peers in the alternative treatment. In a final experiment where student performance on a human anatomy exam was compared between a traditional prosected human cadaver treatment and the alternative clay sculpting treatment, no significant difference were detected, suggesting that the complexity or simplicity of the anatomy representation is less important than the similarity between the learning experience and the testing experience.

Dissecting genome-wide association signals for loss-of-function phenotypes in sorghum flavonoid pigmentation traits

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWAS) are a powerful method to dissect the genetic basis of traits, though in practice the effects of complex genetic architecture and population structure remain poorly understood. To compare mapping strategies we dissect the genetic control of flavonoid pigmentatio...

Synthetic fossilization of soft biological tissues and their shape-preserving transformation into silica or electron-conductive replicas

DOE PAGES

Townson, Jason L.; Lin, Yu-Shen; Chou, Stanley S.; ...

2014-12-08

Structural preservation of complex biological systems from the subcellular to whole organism level in robust forms, enabling dissection and imaging while preserving 3D context, represents an enduring grand challenge in biology. Here we report a simple immersion method for structurally preserving intact organisms via conformal stabilization within silica. This self-limiting process, which we refer to as silica bioreplication, occurs by condensation of water-soluble silicic acid proximally to biomolecular interfaces throughout the organism. Conformal nanoscopic silicification of all biomolecular features imparts structural rigidity enabling the preservation of shape and nano-to-macroscale dimensional features upon drying to form a biocomposite and further highmore » temperature oxidative calcination to form silica replicas or reductive pyrolysis to form electrically conductive carbon replicas of complete organisms. Ultimately, the simplicity and generalizability of this approach should facilitate efforts in biological preservation and analysis and could enable the development of new classes of biomimetic composite materials.« less

Nested association mapping for dissecting complex traits using Peanut 58K SNP array

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWAS) and linkage mapping have been the two most predominant strategies to dissect complex traits, but are limited by the occurrence of false positives reported for GWAS, and low resolution in the case of linkage analysis. This has led to the development of a joint a...

Synthetic Biology: Putting Synthesis into Biology

PubMed Central

Liang, Jing; Luo, Yunzi; Zhao, Huimin

2010-01-01

The ability to manipulate living organisms is at the heart of a range of emerging technologies that serve to address important and current problems in environment, energy, and health. However, with all its complexity and interconnectivity, biology has for many years been recalcitrant to engineering manipulations. The recent advances in synthesis, analysis, and modeling methods have finally provided the tools necessary to manipulate living systems in meaningful ways, and have led to the coining of a field named synthetic biology. The scope of synthetic biology is as complicated as life itself – encompassing many branches of science, and across many scales of application. New DNA synthesis and assembly techniques have made routine the customization of very large DNA molecules. This in turn has allowed the incorporation of multiple genes and pathways. By coupling these with techniques that allow for the modeling and design of protein functions, scientists have now gained the tools to create completely novel biological machineries. Even the ultimate biological machinery – a self-replicating organism – is being pursued at this moment. It is the purpose of this review to dissect and organize these various components of synthetic biology into a coherent picture. PMID:21064036

A Rare Complication of TEVAR Performed for Complex Acute Stanford B Aortic Dissection.

PubMed

Awad, George; Zardo, Patrick; Baraki, Hassina; Kutschka, Ingo

2017-01-01

Management of aortic dissection with a novel endovascular technique known as thoracic endovascular aortic repair (TEVAR) paired with surgical debranching as a less invasive alternative to conventional repair has gained widespread acceptance. However, experience for complicated, Stanford type B dissection involving the aortic arch is still limited.

One-stage hybrid surgery for acute Stanford type A aortic dissection with David operation, aortic arch debranching, and endovascular graft: a case report

PubMed Central

Liu, Lulu; Qin, Chaoyi; Hou, Jianglong; Zhu, Da; Zhang, Bengui; Ma, Hao

2016-01-01

Acute Stanford type A aortic dissection requires an extremely complex surgical strategy and presents high risk of complications. Although many different procedures were reported to treat this aortic dissection, high mortality rate and incidences of complications still exist. This study presents a 59-year-old lady with acute Stanford type A aortic dissection, which originated from the aortic root to proximal part of right external iliac artery and involved the brachiocephalic trunk, left carotid artery, celiac trunk, and left renal artery. The patient underwent one-stage hybrid surgery of David procedures, debranching, and endovascular aortic repair under ultrasound-guided aortic arch cannulation cardiopulmonary bypass (CPB). The surgery was successfully performed, and the patient showed no post-operative complication. The one-staged hybrid surgery of David procedures, debranching, and endovascular aortic repair provides novel and well-designed combined techniques for treating complex acute Stanford type A aortic dissection. Our techniques significantly lowered the risks, thereby expanding the indications of surgical intervention for acute Stanford type A aortic dissection. PMID:28149590

One-stage hybrid surgery for acute Stanford type A aortic dissection with David operation, aortic arch debranching, and endovascular graft: a case report.

PubMed

Liu, Lulu; Qin, Chaoyi; Hou, Jianglong; Zhu, Da; Zhang, Bengui; Ma, Hao; Guo, Yingqiang

2016-12-01

Acute Stanford type A aortic dissection requires an extremely complex surgical strategy and presents high risk of complications. Although many different procedures were reported to treat this aortic dissection, high mortality rate and incidences of complications still exist. This study presents a 59-year-old lady with acute Stanford type A aortic dissection, which originated from the aortic root to proximal part of right external iliac artery and involved the brachiocephalic trunk, left carotid artery, celiac trunk, and left renal artery. The patient underwent one-stage hybrid surgery of David procedures, debranching, and endovascular aortic repair under ultrasound-guided aortic arch cannulation cardiopulmonary bypass (CPB). The surgery was successfully performed, and the patient showed no post-operative complication. The one-staged hybrid surgery of David procedures, debranching, and endovascular aortic repair provides novel and well-designed combined techniques for treating complex acute Stanford type A aortic dissection. Our techniques significantly lowered the risks, thereby expanding the indications of surgical intervention for acute Stanford type A aortic dissection.

Intravital imaging reveals new ancillary mechanisms co-opted by cancer cells to drive tumor progression

PubMed Central

Lucas, Morghan C.; Timpson, Paul

2016-01-01

Intravital imaging is providing new insights into the dynamics of tumor progression in native tissues and has started to reveal the layers of complexity found in cancer. Recent advances in intravital imaging have allowed us to look deeper into cancer behavior and to dissect the interactions between tumor cells and the ancillary host niche that promote cancer development. In this review, we provide an insight into the latest advances in cancer biology achieved by intravital imaging, focusing on recently discovered mechanisms by which tumor cells manipulate normal tissue to facilitate disease progression. PMID:27239290

Cow's Eye Dissection in the Physics Lab.

ERIC Educational Resources Information Center

Lapp, David R.; Keenan, James E.

1991-01-01

Proposes the science demonstration of dissecting a cow's eye to integrate biology and physics in the study of optics and lenses. Reviews the anatomy of the eye, describes the visual process and covers topics as index of refraction of the cornea, microscopic receptors, the lens, and the retina. (MDH)

Bio-Physics Manifesto -- for the Future of Physics and Biology

NASA Astrophysics Data System (ADS)

Oono, Y.

2008-04-01

The Newtonian revolution taught us how to dissect phenomena into contingencies (e.g., initial conditions) and fundamental laws (e.g., equations of motion). Since then, `fundamental physics' has been pursuing purer and leaner fundamental laws. Consequently, to explain real phenomena a lot of auxiliary conditions become required. Isn't it now the time to start studying `auxiliary conditions' seriously? The study of biological systems has a possibility of shedding light on this neglected side of phenomena in physics, because we organisms were constructed by our parents who supplied indispensable auxiliary conditions; we never self-organize. Thus, studying the systems lacking self-organizing capability (such as complex systems) may indicate new directions to physics and biology (biophysics). There have been attempts to construct a `general theoretical framework' of biology, but most of them never seriously looked at the actual biological world. Every serious natural science must start with establishing a phenomenological framework. Therefore, this must be the main part of bio-physics. However, this article is addressed mainly to theoretical physicists and discusses only certain theoretical aspects (with real illustrative examples).

Systems Biology Approaches to the Study of Biological Networks Underlying Alzheimer's Disease: Role of miRNAs.

PubMed

Roth, Wera; Hecker, David; Fava, Eugenio

2016-01-01

MicroRNAs (miRNAs) are emerging as significant regulators of mRNA complexity in the human central nervous system (CNS) thereby controlling distinct gene expression profiles in a spatio-temporal manner during development, neuronal plasticity, aging and (age-related) neurodegeneration, including Alzheimer's disease (AD). Increasing effort is expended towards dissecting and deciphering the molecular and genetic mechanisms of neurobiological and pathological functions of these brain-enriched miRNAs. Along these lines, recent data pinpoint distinct miRNAs and miRNA networks being linked to APP splicing, processing and Aβ pathology (Lukiw et al., Front Genet 3:327, 2013), and furthermore, to the regulation of tau and its cellular subnetworks (Lau et al., EMBO Mol Med 5:1613, 2013), altogether underlying the onset and propagation of Alzheimer's disease. MicroRNA profiling studies in Alzheimer's disease suffer from poor consensus which is an acknowledged concern in the field, and constitutes one of the current technical challenges. Hence, a strong demand for experimental and computational systems biology approaches arises, to incorporate and integrate distinct levels of information and scientific knowledge into a complex system of miRNA networks in the context of the transcriptome, proteome and metabolome in a given cellular environment. Here, we will discuss the state-of-the-art technologies and computational approaches on hand that may lead to a deeper understanding of the complex biological networks underlying the pathogenesis of Alzheimer's disease.

Comparison of oral toxicological properties of botulinum neurotoxin serotypes A and B.

PubMed

Cheng, Luisa W; Henderson, Thomas D

2011-07-01

Botulinum neurotoxins (BoNTs) are among the most potent biological toxins for humans. Of the seven known serotypes (A-G) of BoNT, serotypes A, B and E cause most of the foodborne intoxications in humans. BoNTs in nature are associated with non-toxic accessory proteins known as neurotoxin-associated proteins (NAPs), forming large complexes that have been shown to play important roles in oral toxicity. Using mouse intraperitoneal and oral models of botulism, we determined the dose response to both BoNT/B holotoxin and complex toxins, and compared the toxicities of BoNT/B and BoNT/A complexes. Although serotype A and B complexes have similar NAP composition, BoNT/B formed larger-sized complexes, and was approximately 90 times more lethal in mouse oral intoxications than BoNT/A complexes. When normalized by mean lethal dose, mice orally treated with high doses of BoNT/B complex showed a delayed time-to-death when compared with mice treated with BoNT/A complex. Furthermore, we determined the effect of various food matrices on oral toxicity of BoNT/A and BoNT/B complexes. BoNT/B complexes showed lower oral bioavailability in liquid egg matrices when compared to BoNT/A complexes. In summary, our studies revealed several factors that can either enhance or reduce the toxicity and oral bioavailability of BoNTs. Dissecting the complexities of the different BoNT serotypes and their roles in foodborne botulism will lead to a better understanding of toxin biology and aid future food risk assessments. Published by Elsevier Ltd.

Is there a superior simulator for human anatomy education? How virtual dissection can overcome the anatomic and pedagogic limitations of cadaveric dissection.

PubMed

Darras, Kathryn E; de Bruin, Anique B H; Nicolaou, Savvas; Dahlström, Nils; Persson, Anders; van Merriënboer, Jeroen; Forster, Bruce B

2018-03-23

Educators must select the best tools to teach anatomy to future physicians and traditionally, cadavers have always been considered the "gold standard" simulator for living anatomy. However, new advances in technology and radiology have created new teaching tools, such as virtual dissection, which provide students with new learning opportunities. Virtual dissection is a novel way of studying human anatomy through patient computed tomography (CT) scans. Through touchscreen technology, students can work together in groups to "virtually dissect" the CT scans to better understand complex anatomic relationships. This article presents the anatomic and pedagogic limitations of cadaveric dissection and explains what virtual dissection is and how this new technology may be used to overcome these limitations.

Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle

PubMed Central

Rendl, Michael; Lewis, Lisa

2005-01-01

De novo hair follicle formation in embryonic skin and new hair growth in adult skin are initiated when specialized mesenchymal dermal papilla (DP) cells send cues to multipotent epithelial stem cells. Subsequently, DP cells are enveloped by epithelial stem cell progeny and other cell types to form a niche orchestrating hair growth. Understanding the general biological principles that govern the mesenchymal–epithelial interactions within the DP niche, however, has been hampered so far by the lack of systematic approaches to dissect the complete molecular make-up of this complex tissue. Here, we take a novel multicolor labeling approach, using cell type–specific transgenic expression of red and green fluorescent proteins in combination with immunolabeling of specific antigens, to isolate pure populations of DP and four of its surrounding cell types: dermal fibroblasts, melanocytes, and two different populations of epithelial progenitors (matrix and outer root sheath cells). By defining their transcriptional profiles, we develop molecular signatures characteristic for the DP and its niche. Validating the functional importance of these signatures is a group of genes linked to hair disorders that have been largely unexplored. Additionally, the DP signature reveals novel signaling and transcription regulators that distinguish them from other cell types. The mesenchymal–epithelial signatures include key factors previously implicated in ectodermal-neural fate determination, as well as a myriad of regulators of bone morphogenetic protein signaling. These findings establish a foundation for future functional analyses of the roles of these genes in hair development. Overall, our strategy illustrates how knowledge of the genes uniquely expressed by each cell type residing in a complex niche can reveal important new insights into the biology of the tissue and its associated disease states. PMID:16162033

Biochemical systems approaches for the analysis of histone modification readout.

PubMed

Soldi, Monica; Bremang, Michael; Bonaldi, Tiziana

2014-08-01

Chromatin is the macromolecular nucleoprotein complex that governs the organization of genetic material in the nucleus of eukaryotic cells. In chromatin, DNA is packed with histone proteins into nucleosomes. Core histones are prototypes of hyper-modified proteins, being decorated by a large number of site-specific reversible and irreversible post-translational modifications (PTMs), which contribute to the maintenance and modulation of chromatin plasticity, gene activation, and a variety of other biological processes and disease states. The observations of the variety, frequency and co-occurrence of histone modifications in distinct patterns at specific genomic loci have led to the idea that hPTMs can create a molecular barcode, read by effector proteins that translate it into a specific transcriptional state, or process, on the underlying DNA. However, despite the fact that this histone-code hypothesis was proposed more than 10 years ago, the molecular details of its working mechanisms are only partially characterized. In particular, two questions deserve specific investigation: how the different modifications associate and synergize into patterns and how these PTM configurations are read and translated by multi-protein complexes into a specific functional outcome on the genome. Mass spectrometry (MS) has emerged as a versatile tool to investigate chromatin biology, useful for both identifying and validating hPTMs, and to dissect the molecular determinants of histone modification readout systems. We review here the MS techniques and the proteomics methods that have been developed to address these fundamental questions in epigenetics research, emphasizing approaches based on the proteomic dissection of distinct native chromatin regions, with a critical evaluation of their present challenges and future potential. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of a Dissection Video Clip on Anxiety, Affect, and Self-Efficacy in Educational Dissection: A Treatment Study

PubMed Central

Randler, Christoph; Demirhan, Eda; Wüst-Ackermann, Peter; Desch, Inga H.

2016-01-01

In science education, dissections of animals are an integral part of teaching, but they often evoke negative emotions. We aimed at reducing negative emotions (anxiety, negative affect [NA]) and increasing positive affect (PA) and self-efficacy by an experimental intervention using a predissection video to instruct students about fish dissection. We compared this treatment with another group that watched a life history video about the fish. The participants were 135 students studying to become biology teachers. Seventy received the treatment with the dissection video, and 65 viewed the life history video. We applied a pre/posttest treatment-comparison design and used the Positive and Negative Affect Schedule (PANAS), the State–Trait–Anxiety Inventory for State (STAI-S), and a self-efficacy measure three times: before the lesson (pretest), after the film treatment (posttest 1), and after the dissection (posttest 2). The dissection film group scored higher in PA, NA, and state anxiety (STAI-S) after the dissection video treatment and higher in self-efficacy after the dissection. The life history group showed no differences between the pretest and posttest 1. The dissection film has clear benefits—increasing PA and self-efficacy—that come at the cost of higher NA and higher STAI-S. PMID:27290738

Influence of a Dissection Video Clip on Anxiety, Affect, and Self-Efficacy in Educational Dissection: A Treatment Study.

PubMed

Randler, Christoph; Demirhan, Eda; Wüst-Ackermann, Peter; Desch, Inga H

2016-01-01

In science education, dissections of animals are an integral part of teaching, but they often evoke negative emotions. We aimed at reducing negative emotions (anxiety, negative affect [NA]) and increasing positive affect (PA) and self-efficacy by an experimental intervention using a predissection video to instruct students about fish dissection. We compared this treatment with another group that watched a life history video about the fish. The participants were 135 students studying to become biology teachers. Seventy received the treatment with the dissection video, and 65 viewed the life history video. We applied a pre/posttest treatment-comparison design and used the Positive and Negative Affect Schedule (PANAS), the State-Trait-Anxiety Inventory for State (STAI-S), and a self-efficacy measure three times: before the lesson (pretest), after the film treatment (posttest 1), and after the dissection (posttest 2). The dissection film group scored higher in PA, NA, and state anxiety (STAI-S) after the dissection video treatment and higher in self-efficacy after the dissection. The life history group showed no differences between the pretest and posttest 1. The dissection film has clear benefits - increasing PA and self-efficacy - that come at the cost of higher NA and higher STAI-S.

Cancer systems biology in the genome sequencing era: part 1, dissecting and modeling of tumor clones and their networks.

PubMed

Wang, Edwin; Zou, Jinfeng; Zaman, Naif; Beitel, Lenore K; Trifiro, Mark; Paliouras, Miltiadis

2013-08-01

Recent tumor genome sequencing confirmed that one tumor often consists of multiple cell subpopulations (clones) which bear different, but related, genetic profiles such as mutation and copy number variation profiles. Thus far, one tumor has been viewed as a whole entity in cancer functional studies. With the advances of genome sequencing and computational analysis, we are able to quantify and computationally dissect clones from tumors, and then conduct clone-based analysis. Emerging technologies such as single-cell genome sequencing and RNA-Seq could profile tumor clones. Thus, we should reconsider how to conduct cancer systems biology studies in the genome sequencing era. We will outline new directions for conducting cancer systems biology by considering that genome sequencing technology can be used for dissecting, quantifying and genetically characterizing clones from tumors. Topics discussed in Part 1 of this review include computationally quantifying of tumor subpopulations; clone-based network modeling, cancer hallmark-based networks and their high-order rewiring principles and the principles of cell survival networks of fast-growing clones. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans.

PubMed

Andrusiak, Matthew G; Jin, Yishi

2016-04-08

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundwormCaenorhabditis eleganswas developed as a system to study genes required for development and nervous system function. The powerful genetics ofC. elegansin combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components inC. elegans. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Standardized Profiling of The Membrane-Enriched Proteome of Mouse Dorsal Root Ganglia (DRG) Provides Novel Insights Into Chronic Pain.

PubMed

Rouwette, Tom; Sondermann, Julia; Avenali, Luca; Gomez-Varela, David; Schmidt, Manuela

2016-06-01

Chronic pain is a complex disease with limited treatment options. Several profiling efforts have been employed with the aim to dissect its molecular underpinnings. However, generated results are often inconsistent and nonoverlapping, which is largely because of inherent technical constraints. Emerging data-independent acquisition (DIA)-mass spectrometry (MS) has the potential to provide unbiased, reproducible and quantitative proteome maps - a prerequisite for standardization among experiments. Here, we designed a DIA-based proteomics workflow to profile changes in the abundance of dorsal root ganglia (DRG) proteins in two mouse models of chronic pain, inflammatory and neuropathic. We generated a DRG-specific spectral library containing 3067 DRG proteins, which enables their standardized quantification by means of DIA-MS in any laboratory. Using this resource, we profiled 2526 DRG proteins in each biological replicate of both chronic pain models and respective controls with unprecedented reproducibility. We detected numerous differentially regulated proteins, the majority of which exhibited pain model-specificity. Our approach recapitulates known biology and discovers dozens of proteins that have not been characterized in the somatosensory system before. Functional validation experiments and analysis of mouse pain behaviors demonstrate that indeed meaningful protein alterations were discovered. These results illustrate how the application of DIA-MS can open new avenues to achieve the long-awaited standardization in the molecular dissection of pathologies of the somatosensory system. Therefore, our findings provide a valuable framework to qualitatively extend our understanding of chronic pain and somatosensation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Computer-Based Learning Packages Have a Role, but Care Needs to Be Given as to When They Are Delivered

ERIC Educational Resources Information Center

Quinn, Joseph G.; King, Karen; Roberts, David; Carey, Linda; Mousley, Angela

2009-01-01

It is compulsory for first year biological science students at Queens University Belfast to complete a range of assessed, laboratory-based practicals in various scientific procedures including dissection. This study investigates student performance and attitudes when they have to complete a traditional dissection and a computer based learning…

The Influence of Emotion on Students' Performance in Dissection Exercises

ERIC Educational Resources Information Center

Holstermann, Nina; Grube, Dietmar; Bogeholz, Susanne

2009-01-01

This paper investigates the issue of how emotions such as disgust influence students' self-efficacy belief in terms of mastering a dissection task and also how these affect their interest in the biology of the heart. Following models of intrinsic motivation and the development of motivation, we expected disgust to negatively impact on students'…

Investment in plant research and development bears fruit in China.

PubMed

Chong, Kang; Xu, Zhihong

2014-04-01

Recent rapid progress in plant science and biotechnology in China demonstrates that China's stronger support for funding in plant research and development (R&D) has borne fruit. Chinese groups have contributed major advances in a range of fields, such as rice biology, plant hormone and developmental biology, genomics and evolution, plant genetics and epigenetics, as well as plant biotechnology. Strigolactone studies including those identifying its receptor and dissecting its complex structure and signaling are representative of the recent researches from China at the forefront of the field. These advances are attributable in large part to interdisciplinary studies among scientists from plant science, chemistry, bioinformatics, structural biology, and agronomy. The platforms provided by national facilities facilitate this collaboration. As well, efficient restructuring of the top-down organization of state programs and free exploration of scientists' interests have accelerated achievements by Chinese researchers. Here, we provide a general outline of China's progress in plant R&D to highlight fields in which Chinese research has made significant contributions.

Cognitive Load in Mastoidectomy Skills Training: Virtual Reality Simulation and Traditional Dissection Compared.

PubMed

Andersen, Steven Arild Wuyts; Mikkelsen, Peter Trier; Konge, Lars; Cayé-Thomasen, Per; Sørensen, Mads Sølvsten

2016-01-01

The cognitive load (CL) theoretical framework suggests that working memory is limited, which has implications for learning and skills acquisition. Complex learning situations such as surgical skills training can potentially induce a cognitive overload, inhibiting learning. This study aims to compare CL in traditional cadaveric dissection training and virtual reality (VR) simulation training of mastoidectomy. A prospective, crossover study. Participants performed cadaveric dissection before VR simulation of the procedure or vice versa. CL was estimated by secondary-task reaction time testing at baseline and during the procedure in both training modalities. The national Danish temporal bone course. A total of 40 novice otorhinolaryngology residents. Reaction time was increased by 20% in VR simulation training and 55% in cadaveric dissection training of mastoidectomy compared with baseline measurements. Traditional dissection training increased CL significantly more than VR simulation training (p < 0.001). VR simulation training imposed a lower CL than traditional cadaveric dissection training of mastoidectomy. Learning complex surgical skills can be a challenge for the novice and mastoidectomy skills training could potentially be optimized by employing VR simulation training first because of the lower CL. Traditional dissection training could then be used to supplement skills training after basic competencies have been acquired in the VR simulation. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

PubMed

Niu, Guoqing; Tan, Huarong

2015-02-01

The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics. Copyright © 2014. Published by Elsevier Ltd.

Network Analysis Reveals Putative Genes Affecting Meat Quality in Angus Cattle.

PubMed

Mateescu, Raluca G; Garrick, Dorian J; Reecy, James M

2017-01-01

Improvements in eating satisfaction will benefit consumers and should increase beef demand which is of interest to the beef industry. Tenderness, juiciness, and flavor are major determinants of the palatability of beef and are often used to reflect eating satisfaction. Carcass qualities are used as indicator traits for meat quality, with higher quality grade carcasses expected to relate to more tender and palatable meat. However, meat quality is a complex concept determined by many component traits making interpretation of genome-wide association studies (GWAS) on any one component challenging to interpret. Recent approaches combining traditional GWAS with gene network interactions theory could be more efficient in dissecting the genetic architecture of complex traits. Phenotypic measures of 23 traits reflecting carcass characteristics, components of meat quality, along with mineral and peptide concentrations were used along with Illumina 54k bovine SNP genotypes to derive an annotated gene network associated with meat quality in 2,110 Angus beef cattle. The efficient mixed model association (EMMAX) approach in combination with a genomic relationship matrix was used to directly estimate the associations between 54k SNP genotypes and each of the 23 component traits. Genomic correlated regions were identified by partial correlations which were further used along with an information theory algorithm to derive gene network clusters. Correlated SNP across 23 component traits were subjected to network scoring and visualization software to identify significant SNP. Significant pathways implicated in the meat quality complex through GO term enrichment analysis included angiogenesis, inflammation, transmembrane transporter activity, and receptor activity. These results suggest that network analysis using partial correlations and annotation of significant SNP can reveal the genetic architecture of complex traits and provide novel information regarding biological mechanisms and genes that lead to complex phenotypes, like meat quality, and the nutritional and healthfulness value of beef. Improvements in genome annotation and knowledge of gene function will contribute to more comprehensive analyses that will advance our ability to dissect the complex architecture of complex traits.

Positional cloning in mice and its use for molecular dissection of inflammatory arthritis.

PubMed

Abe, Koichiro; Yu, Philipp

2009-02-01

One of the upcoming next quests in the field of genetics might be molecular dissection of the genetic and environmental components of human complex diseases. In humans, however, there are certain experimental limitations for identification of a single component of the complex interactions by genetic analyses. Experimental animals offer simplified models for genetic and environmental interactions in human complex diseases. In particular, mice are the best mammalian models because of a long history and ample experience for genetic analyses. Forward genetics, which includes genetic screen and subsequent positional cloning of the causative genes, is a powerful strategy to dissect a complex phenomenon without preliminarily molecular knowledge of the process. In this review, first, we describe a general scheme of positional cloning in mice. Next, recent accomplishments on the patho-mechanisms of inflammatory arthritis by forward genetics approaches are introduced; Positional cloning effort for skg, Ali5, Ali18, cmo, and lupo mutants are provided as examples for the application to human complex diseases. As seen in the examples, the identification of genetic factors by positional cloning in the mouse have potential in solving molecular complexity of gene-environment interactions in human complex diseases.

Retrograde renal hilar dissection and segmental arterial clamping: a simple modification to achieve super-selective robotic partial nephrectomy.

PubMed

Greene, Richard N; Sutherland, Douglas E; Tausch, Timothy J; Perez, Deo S

2014-03-01

Super-selective vascular control prior to robotic partial nephrectomy (also known as 'zero-ischemia') is a novel surgical technique that promises to reduce warm ischemia time. The technique has been shown to be feasible but adds substantial technical complexity and cost to the procedure. We present a simplified retrograde dissection of the renal hilum to achieve selective vascular control during robotic partial nephrectomy. Consecutive patients with stage 1 solid and complex cystic renal masses underwent robotic partial nephrectomies with selective vascular control using a modification to previously described super-selective robotic partial nephrectomy. In each case, the renal arterial branch supplying the mass and surrounding parenchyma was dissected in a retrograde fashion from the tumor. Intra-renal dissection of the interlobular artery was not performed. Intra-operative immunofluorescence was not utilized as assessment of parenchymal ischemia was documented before partial nephrectomy. Data was prospectively collected in an IRB-approved partial nephrectomy database. Operative variables between patients undergoing super-selective versus standard robotic partial nephrectomy were compared. Super-selective partial nephrectomy with retrograde hilar dissection was successfully completed in five consecutive patients. There were no complications or conversions to traditional partial nephrectomy. All were diagnosed with renal cell carcinoma and surgical margins were all negative. Estimated blood loss, warm ischemia time, operative time and length of stay were all comparable between patients undergoing super-selective and standard robotic partial nephrectomy. Retrograde hilar dissection appears to be a feasible and safe approach to super-selective partial nephrectomy without adding complex renovascular surgical techniques or cost to the procedure.

Arabidopsis P-glycoprotein19 participates in the inhibition of gravitropism by gravacin.

PubMed

Rojas-Pierce, Marcela; Titapiwatanakun, Boosaree; Sohn, Eun Ju; Fang, Fang; Larive, Cynthia K; Blakeslee, Joshua; Cheng, Yan; Cutler, Sean R; Cuttler, Sean; Peer, Wendy A; Murphy, Angus S; Raikhel, Natasha V

2007-12-01

ATP-binding cassette (ABC) transporters have been implicated in a multitude of biological pathways. In plants, some ABC transporters are involved in the polar transport of the plant hormone auxin and the gravitropic response. We previously identified Gravacin as a potent inhibitor of gravitropism in Arabidopsis thaliana. We demonstrate that P-glycoprotein19 (PGP19) is a target for Gravacin and participates in its inhibition of gravitropism. Gravacin inhibited the auxin transport activity of PGP19 and PGP19-PIN complexes. Furthermore, we identified E1174 as an important residue for PGP19 activity and its ability to form active transport complexes with PIN1. Gravacin is an auxin transport inhibitor that inhibits PGPs, particularly PGP19, which can be used to further dissect the role of PGP19 without the inhibition of other auxin transporters, namely PIN proteins.

Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation

PubMed Central

Rihel, Jason; Prober, David A.; Arvanites, Anthony; Lam, Kelvin; Zimmerman, Steven; Jang, Sumin; Haggarty, Stephen J.; Kokel, David; Rubin, Lee L.; Peterson, Randall T.; Schier, Alexander F.

2010-01-01

A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multi-dimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go-related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors. PMID:20075256

There Is More to the Dissection of a Pig's Heart

ERIC Educational Resources Information Center

Lee, Yeung Chung

2004-01-01

The dissection of the mammalian heart in secondary biology classes need not be restricted to revealing the internal structure of the heart and its function. It could also be used to demonstrate other important aspects of blood circulation, including the blood supply to the heart itself as well as the causes and effects of coronary heart disease.…

Subclavian artery dissection during diagnostic cardiac catheterization: the role of conservative management.

PubMed

Frohwein, S; Ververis, J J; Marshall, J J

1995-04-01

Dissection of the subclavian artery during routine cardiac catheterization while obtaining cannulation to the left internal mammary artery is an unusual complication and to our knowledge has never been reported. Conservative management of this vascular injury can avoid the sequelae of high-risk surgical repairs made difficult by a complex operative exposure. We describe a case in which dissection of the left subclavian artery was treated conservatively with an excellent outcome.

Entropy in molecular recognition by proteins

PubMed Central

Caro, José A.; Harpole, Kyle W.; Kasinath, Vignesh; Lim, Jackwee; Granja, Jeffrey; Valentine, Kathleen G.; Sharp, Kim A.

2017-01-01

Molecular recognition by proteins is fundamental to molecular biology. Dissection of the thermodynamic energy terms governing protein–ligand interactions has proven difficult, with determination of entropic contributions being particularly elusive. NMR relaxation measurements have suggested that changes in protein conformational entropy can be quantitatively obtained through a dynamical proxy, but the generality of this relationship has not been shown. Twenty-eight protein–ligand complexes are used to show a quantitative relationship between measures of fast side-chain motion and the underlying conformational entropy. We find that the contribution of conformational entropy can range from favorable to unfavorable, which demonstrates the potential of this thermodynamic variable to modulate protein–ligand interactions. For about one-quarter of these complexes, the absence of conformational entropy would render the resulting affinity biologically meaningless. The dynamical proxy for conformational entropy or “entropy meter” also allows for refinement of the contributions of solvent entropy and the loss in rotational-translational entropy accompanying formation of high-affinity complexes. Furthermore, structure-based application of the approach can also provide insight into long-lived specific water–protein interactions that escape the generic treatments of solvent entropy based simply on changes in accessible surface area. These results provide a comprehensive and unified view of the general role of entropy in high-affinity molecular recognition by proteins. PMID:28584100

Entropy in molecular recognition by proteins.

PubMed

Caro, José A; Harpole, Kyle W; Kasinath, Vignesh; Lim, Jackwee; Granja, Jeffrey; Valentine, Kathleen G; Sharp, Kim A; Wand, A Joshua

2017-06-20

Molecular recognition by proteins is fundamental to molecular biology. Dissection of the thermodynamic energy terms governing protein-ligand interactions has proven difficult, with determination of entropic contributions being particularly elusive. NMR relaxation measurements have suggested that changes in protein conformational entropy can be quantitatively obtained through a dynamical proxy, but the generality of this relationship has not been shown. Twenty-eight protein-ligand complexes are used to show a quantitative relationship between measures of fast side-chain motion and the underlying conformational entropy. We find that the contribution of conformational entropy can range from favorable to unfavorable, which demonstrates the potential of this thermodynamic variable to modulate protein-ligand interactions. For about one-quarter of these complexes, the absence of conformational entropy would render the resulting affinity biologically meaningless. The dynamical proxy for conformational entropy or "entropy meter" also allows for refinement of the contributions of solvent entropy and the loss in rotational-translational entropy accompanying formation of high-affinity complexes. Furthermore, structure-based application of the approach can also provide insight into long-lived specific water-protein interactions that escape the generic treatments of solvent entropy based simply on changes in accessible surface area. These results provide a comprehensive and unified view of the general role of entropy in high-affinity molecular recognition by proteins.

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†

PubMed Central

Kirsten, Holger; Al-Hasani, Hoor; Holdt, Lesca; Gross, Arnd; Beutner, Frank; Krohn, Knut; Horn, Katrin; Ahnert, Peter; Burkhardt, Ralph; Reiche, Kristin; Hackermüller, Jörg; Löffler, Markus; Teupser, Daniel; Thiery, Joachim; Scholz, Markus

2015-01-01

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes. PMID:26019233

Multilayered Genetic and Omics Dissection of Mitochondrial Activity in a Mouse Reference Population

PubMed Central

Wu, Yibo; Williams, Evan G.; Dubuis, Sébastien; Mottis, Adrienne; Jovaisaite, Virginija; Houten, Sander M.; Argmann, Carmen A.; Faridi, Pouya; Wolski, Witold; Kutalik, Zoltán; Zamboni, Nicola; Auwerx, Johan; Aebersold, Ruedi

2014-01-01

SUMMARY The manner by which genotype and environment affect complex phenotypes is one of the fundamental questions in biology. In this study, we quantified the transcriptome—a subset of the metabolome—and, using targeted proteomics, quantified a subset of the liver proteome from 40 strains of the BXD mouse genetic reference population on two diverse diets. We discovered dozens of transcript, protein, and metabolite QTLs, several of which linked to metabolic phenotypes. Most prominently, Dhtkd1 was identified as a primary regulator of 2-aminoadipate, explaining variance in fasted glucose and diabetes status in both mice and humans. These integrated molecular profiles also allowed further characterization of complex pathways, particularly the mitochondrial unfolded protein response (UPRmt). UPRmt shows strikingly variant responses at the transcript and protein level that are remarkably conserved among C. elegans, mice, and humans. Overall, these examples demonstrate the value of an integrated multilayered omics approach to characterize complex metabolic phenotypes. PMID:25215496

[Robot-assisted Pylorus-Preserving Partial Pancreaticoduodenectomy (Kausch-Whipple Procedure)].

PubMed

Aselmann, H; Egberts, J-H; Hinz, S; Jünemann, K-P; Becker, T

2016-04-01

The surgical treatment of pancreatic head tumours is one of the most complex procedures in general surgery. In contrast to colorectal surgery, minimally-invasive techniques are not very commonly applied in pancreatic surgery. Both the delicate dissection along peri- and retropancreatic vessels and the extrahepatic bile ducts and subsequent reconstruction are very demanding with rigid standard laparoscopic instruments. The 4-arm robotic surgery system with angled instruments, unidirectional movement of instruments with adjustable transmission, tremor elimination and a stable, surgeon-controlled 3D-HD view is a promising platform to overcome the limitations of standard laparoscopic surgery regarding precise dissection and reconstruction in pancreatic surgery. Pancreatic head resection for mixed-type IPMN of the pancreatic head. Robot-assisted, minimally-invasive pylorus-preserving pancreaticoduodenectomy (Kausch-Whipple procedure). The robotic approach is particularly suited for complex procedures such as pylorus-preserving pancreatic head resections. The fully robotic Kausch-Whipple procedure is technically feasible and safe. The advantages of the robotic system are apparent in the delicate dissection near vascular structures, in lymph node dissection, the precise dissection of the uncinate process and, especially, bile duct and pancreatic anastomosis. Georg Thieme Verlag KG Stuttgart · New York.

Aortocoronary dissection with acute left main artery occlusion: successful treatment with emergent stenting.

PubMed

Wykrzykowska, Joanna J; Carrozza, Joseph; Laham, Roger J

2006-08-01

Iatrogenic aortocoronary dissection is a rare but devastating complication of percutaneous coronary interventions and cardiac surgery, with a mortality rate up to 35%. Of the type-A dissections in the International Registry of Aortic Dissections (IRAD), 27% were caused by coronary interventions. The mechanism involves an initial dissection in the coronary artery, which then propagates in a retrograde fashion past the sinuses of Valsalva, often several centimeters beyond the aortic valve. With the advent of complex interventions such as left main stent implantation, revascularization of chronic total occlusions and mechanical thrombectomy, this complication may become more prevalent. Here we present a unique case of percutaneous coronary intervention (PCI) of the left circumflex (LCx) artery complicated by a left main coronary dissection that propagated approximately 8 cm into the ascending aorta and caused abrupt left main coronary artery occlusion and hemodynamic collapse. Rescue of the left main artery and sealing of the aortic dissection with stabilization of the patient was possible with rapid ostial left main artery stenting.

Does the end justify the means? The contemporary role of dissection/re-entry strategies for recanalization of coronary chronic total occlusions.

PubMed

Karatasakis, Aris; Brilakis, Emmanouil S

2017-11-01

Antegrade and retrograde dissection/re-entry techniques are frequently utilized in contemporary CTO PCI, especially for complex lesions. One-year outcomes with modern dissection/re-entry techniques appear favorable and comparable with those achieved after intraplaque crossing, supporting their increased use. Randomized data on the procedural safety, efficiency, and long-term outcomes of subadventitial CTO PCI techniques are needed. © 2017 Wiley Periodicals, Inc.

Association weight matrix for the genetic dissection of puberty in beef cattle.

PubMed

Fortes, Marina R S; Reverter, Antonio; Zhang, Yuandan; Collis, Eliza; Nagaraj, Shivashankar H; Jonsson, Nick N; Prayaga, Kishore C; Barris, Wes; Hawken, Rachel J

2010-08-03

We describe a systems biology approach for the genetic dissection of complex traits based on applying gene network theory to the results from genome-wide associations. The associations of single-nucleotide polymorphisms (SNP) that were individually associated with a primary phenotype of interest, age at puberty in our study, were explored across 22 related traits. Genomic regions were surveyed for genes harboring the selected SNP. As a result, an association weight matrix (AWM) was constructed with as many rows as genes and as many columns as traits. Each {i, j} cell value in the AWM corresponds to the z-score normalized additive effect of the ith gene (via its neighboring SNP) on the jth trait. Columnwise, the AWM recovered the genetic correlations estimated via pedigree-based restricted maximum-likelihood methods. Rowwise, a combination of hierarchical clustering, gene network, and pathway analyses identified genetic drivers that would have been missed by standard genome-wide association studies. Finally, the promoter regions of the AWM-predicted targets of three key transcription factors (TFs), estrogen-related receptor gamma (ESRRG), Pal3 motif, bound by a PPAR-gamma homodimer, IR3 sites (PPARG), and Prophet of Pit 1, PROP paired-like homeobox 1 (PROP1), were surveyed to identify binding sites corresponding to those TFs. Applied to our case, the AWM results recapitulate the known biology of puberty, captured experimentally validated binding sites, and identified candidate genes and gene-gene interactions for further investigation.

Association weight matrix for the genetic dissection of puberty in beef cattle

PubMed Central

Fortes, Marina R. S.; Reverter, Antonio; Zhang, Yuandan; Collis, Eliza; Nagaraj, Shivashankar H.; Jonsson, Nick N.; Prayaga, Kishore C.; Barris, Wes; Hawken, Rachel J.

2010-01-01

We describe a systems biology approach for the genetic dissection of complex traits based on applying gene network theory to the results from genome-wide associations. The associations of single-nucleotide polymorphisms (SNP) that were individually associated with a primary phenotype of interest, age at puberty in our study, were explored across 22 related traits. Genomic regions were surveyed for genes harboring the selected SNP. As a result, an association weight matrix (AWM) was constructed with as many rows as genes and as many columns as traits. Each {i, j} cell value in the AWM corresponds to the z-score normalized additive effect of the ith gene (via its neighboring SNP) on the jth trait. Columnwise, the AWM recovered the genetic correlations estimated via pedigree-based restricted maximum-likelihood methods. Rowwise, a combination of hierarchical clustering, gene network, and pathway analyses identified genetic drivers that would have been missed by standard genome-wide association studies. Finally, the promoter regions of the AWM-predicted targets of three key transcription factors (TFs), estrogen-related receptor γ (ESRRG), Pal3 motif, bound by a PPAR-γ homodimer, IR3 sites (PPARG), and Prophet of Pit 1, PROP paired-like homeobox 1 (PROP1), were surveyed to identify binding sites corresponding to those TFs. Applied to our case, the AWM results recapitulate the known biology of puberty, captured experimentally validated binding sites, and identified candidate genes and gene–gene interactions for further investigation. PMID:20643938

Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response

PubMed Central

McKibbin, Craig; Mares, Alina; Piacenti, Michela; Williams, Helen; Roboti, Peristera; Puumalainen, Marjo; Callan, Anna C.; Lesiak-Mieczkowska, Karolina; Linder, Stig; Harant, Hanna; High, Stephen; Flitsch, Sabine L.; Whitehead, Roger C.; Swanton, Eileithyia

2011-01-01

Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel mechanism that contributes to UPR activation. PMID:22145777

Rapidly evolving homing CRISPR barcodes

PubMed Central

Kalhor, Reza; Mali, Prashant; Church, George M.

2017-01-01

We present here an approach for engineering evolving DNA barcodes in living cells. The methodology entails using a homing guide RNA (hgRNA) scaffold that directs the Cas9-hgRNA complex to target the DNA locus of the hgRNA itself. We show that this homing CRISPR-Cas9 system acts as an expressed genetic barcode that diversifies its sequence and that the rate of diversification can be controlled in cultured cells. We further evaluate these barcodes in cell populations and show the barcode RNAs can be assayed as single molecules in situ . This integrated approach will have wide ranging applications, such as in deep lineage tracing, cellular barcoding, molecular recording, dissecting cancer biology, and connectome mapping. PMID:27918539

Techniques for Preservation of the Frontotemporal Branch of Facial Nerve during Orbitozygomatic Approaches

PubMed Central

Spiriev, Toma; Poulsgaard, Lars; Fugleholm, Kaare

2014-01-01

Background During orbitozygomatic (OZ) approaches, the frontotemporal branch (FTB) of the facial nerve is exposed to injury if proper measures are not taken. This article describes in detail the nuances of the two most common techniques (interfascial and subfascial dissection). Design The FTB of the facial nerve was dissected and followed in its tissue planes on fresh-frozen cadaver heads. The interfascial and subfascial dissections were performed, and every step was photographed and examined. Results The interfascial dissection is safe to be started from the most anterior part of the superior temporal line and followed to the root of the zygoma. The dissection is continued on the deep temporalis fascia (DTF), and the interfascial fat pad is elevated. With the subfascial dissection, both the superficial temporalis fascia and the DTF are elevated. The interfascial dissection exposes the zygomatic arch directly, whereas the subfascial dissection requires an additional cut on the DTF to expose the zygomatic arch. Proper subperiosteal dissection on the zygomatic arch is another important step in FTB preservation. Conclusion Detailed understanding of the complex relationship of the tissue planes in the frontotemporal region is needed to perform OZ exposures safely. PMID:26225300

Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research.

PubMed

Kalueff, Allan V; Echevarria, David J; Homechaudhuri, Sumit; Stewart, Adam Michael; Collier, Adam D; Kaluyeva, Aleksandra A; Li, Shaomin; Liu, Yingcong; Chen, Peirong; Wang, JiaJia; Yang, Lei; Mitra, Anisa; Pal, Subharthi; Chaudhuri, Adwitiya; Roy, Anwesha; Biswas, Missidona; Roy, Dola; Podder, Anupam; Poudel, Manoj K; Katare, Deepshikha P; Mani, Ruchi J; Kyzar, Evan J; Gaikwad, Siddharth; Nguyen, Michael; Song, Cai

2016-01-01

Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other 'omics' (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. Copyright © 2015 Elsevier B.V. All rights reserved.

Deconstructing and constructing innate immune functions using molecular sensors and actuators

NASA Astrophysics Data System (ADS)

Coutinho, Kester; Inoue, Takanari

2016-05-01

White blood cells such as neutrophils and macrophages are made competent for chemotaxis and phagocytosis -- the dynamic cellular behaviors that are hallmarks of their innate immune functions -- by the reorganization of complex biological circuits during differentiation. Conventional loss-of-function approaches have revealed that more than 100 genes participate in these cellular functions, and we have begun to understand the intricate signaling circuits that are built up from these gene products. We now appreciate: (1) that these circuits come in a variety of flavors -- so that we can make a distinction between genetic circuits, metabolic circuits and signaling circuits; and (2) that they are usually so complex that the assumption of multiple feedback loops, as well as that of crosstalk between seemingly independent pathways, is now routine. It has not escaped our notice, however, that just as physicists and electrical engineers have long been able to disentangle complex electric circuits simply by repetitive cycles of probing and measuring electric currents using a voltmeter, we might similarly be able to dissect these intricate biological circuits by incorporating equivalent approaches in the fields of cell biology and bioengineering. Existing techniques in biology for probing individual circuit components are unfortunately lacking, so that the overarching goal of drawing an exact circuit diagram for the whole cell -- complete with kinetic parameters for connections between individual circuit components -- is not yet in near sight. My laboratory and others have thus begun the development of a new series of molecular tools that can measurably investigate the circuit connectivity inside living cells, as if we were doing so on a silicon board. In these proceedings, I will introduce some of these techniques, provide examples of their implementation, and offer a perspective on directions moving forward.

``Dissection'' of a Hair Dryer

NASA Astrophysics Data System (ADS)

Eisenstein, Stan; Simpson, Jeff

2008-12-01

The electrical design of the common hair dryer is based almost entirely on relatively simple principles learned in introductory physics classes. Just as biology students dissect a frog to see the principles of anatomy in action, physics students can "dissect" a hair dryer to see how principles of electricity are used in a real system. They can discover how engineers solve problems such as how to vary between low and high heat and fan speed by simply moving the position of a single switch. Principles of alternating versus direct current, series and parallel circuits, electrical safety, voltage dividing, ac rectification, power, and measurement of resistance and continuity all come in to play.

Building mental models by dissecting physical models.

PubMed

Srivastava, Anveshna

2016-01-01

When students build physical models from prefabricated components to learn about model systems, there is an implicit trade-off between the physical degrees of freedom in building the model and the intensity of instructor supervision needed. Models that are too flexible, permitting multiple possible constructions require greater supervision to ensure focused learning; models that are too constrained require less supervision, but can be constructed mechanically, with little to no conceptual engagement. We propose "model-dissection" as an alternative to "model-building," whereby instructors could make efficient use of supervisory resources, while simultaneously promoting focused learning. We report empirical results from a study conducted with biology undergraduate students, where we demonstrate that asking them to "dissect" out specific conceptual structures from an already built 3D physical model leads to a significant improvement in performance than asking them to build the 3D model from simpler components. Using questionnaires to measure understanding both before and after model-based interventions for two cohorts of students, we find that both the "builders" and the "dissectors" improve in the post-test, but it is the latter group who show statistically significant improvement. These results, in addition to the intrinsic time-efficiency of "model dissection," suggest that it could be a valuable pedagogical tool. © 2015 The International Union of Biochemistry and Molecular Biology.

Repetition rate dependency of low-density plasma effects during femtosecond-laser-based surgery of biological tissue

NASA Astrophysics Data System (ADS)

Kuetemeyer, K.; Baumgart, J.; Lubatschowski, H.; Heisterkamp, A.

2009-11-01

Femtosecond laser based nanosurgery of biological tissue is usually done in two different regimes. Depending on the application, low kHz repetition rates above the optical breakdown threshold or high MHz repetition rates in the low-density plasma regime are used. In contrast to the well understood optical breakdown, mechanisms leading to dissection below this threshold are not well known due to the complexity of chemical effects with high numbers of interacting molecules. Furthermore, the laser repetition rate may influence their efficiency. In this paper, we present our study on low-density plasma effects in biological tissue depending on repetition rate by static exposure of porcine corneal stroma to femtosecond pulses. We observed a continuous increase of the laser-induced damage with decreasing repetition rate over two orders of magnitude at constant numbers of applied laser pulses or constant laser pulse energies. Therefore, low repetition rates in the kHz regime are advantageous to minimize the total delivered energy to biological tissue during femtosecond laser irradiation. However, due to frequent excessive damage in this regime directly above the threshold, MHz repetition rates are preferable to create nanometer-sized cuts in the low-density plasma regime.

Does case misclassification threaten the validity of studies investigating the relationship between neck manipulation and vertebral artery dissection stroke? Yes.

PubMed

Paulus, Jessica K; Thaler, David E

2016-01-01

For patients and health care providers who are considering spinal manipulative therapy of the neck, it is crucial to establish if it is a trigger for cervical artery dissection and/or stroke, and if it is, the magnitude of the risk. We discuss the biological plausibility of how neck manipulation could cause cervical artery dissection. We also discuss how case misclassification threatens the validity of influential published studies that have investigated the relationship between neck manipulation and dissection. Our position is supported by the fact that the largest epidemiologic studies of neck manipulation safety with respect to neurological outcomes have relied on International Classification of Diseases-9 codes for case identification. However, the application of these codes in prior studies failed to identify dissections (rather than strokes in general) and so conclusions from those studies are invalid. There are several methodological challenges to understanding the association between neck manipulation and vertebral artery dissection. Addressing these issues is critical because even a modest association between neck manipulation and cervical artery dissection could translate into a significant number of avoidable dissections given the widespread use of neck manipulation by providers from various backgrounds. We believe that valid case classification, accurate measurement of manipulative procedures, and addressing reverse causation bias should be top priorities for future research.

Standard methods for Apis mellifera anatomy and dissection

USDA-ARS?s Scientific Manuscript database

An understanding of the anatomy and functions of internal and external structures are fundamental to many studies on the honey bee Apis mellifera. Similarly, proficiency in dissection techniques is vital for many more complex procedures. In this paper, which is a prelude to the other papers of the C...

Geometric Triangular Chiral Hexagon Crystal-Like Complexes Organization in Pathological Tissues Biological Collision Order

PubMed Central

Díaz, Jairo A.; Jaramillo, Natalia A.; Murillo, Mauricio F.

2007-01-01

The present study describes and documents self-assembly of geometric triangular chiral hexagon crystal like complex organizations (GTCHC) in human pathological tissues.The authors have found this architectural geometric expression at macroscopic and microscopic levels mainly in cancer processes. This study is based essentially on macroscopic and histopathologic analyses of 3000 surgical specimens: 2600 inflammatory lesions and 400 malignant tumours. Geometric complexes identified photographically at macroscopic level were located in the gross surgical specimen, and these areas were carefully dissected. Samples were taken to carry out histologic analysis. Based on the hypothesis of a collision genesis mechanism and because it is difficult to carry out an appropriate methodological observation in biological systems, the authors designed a model base on other dynamic systems to obtain indirect information in which a strong white flash wave light discharge, generated by an electronic device, hits over the lines of electrical conductance structured in helicoidal pattern. In their experimental model, the authors were able to reproduce and to predict polarity, chirality, helicoid geometry, triangular and hexagonal clusters through electromagnetic sequential collisions. They determined that similar events among constituents of extracelular matrix which drive and produce piezoelectric activity are responsible for the genesis of GTCHC complexes in pathological tissues. This research suggests that molecular crystals represented by triangular chiral hexagons derived from a collision-attraction event against collagen type I fibrils emerge at microscopic and macroscopic scales presenting a lateral assembly of each side of hypertrophy helicoid fibers, that represent energy flow in cooperative hierarchically chiral electromagnetic interaction in pathological tissues and arises as a geometry of the equilibrium in perturbed biological systems. Further interdisciplinary studies must be carried out to reproduce, manipulate and amplify their activity and probably use them as a base to develop new therapeutic strategies in cancer. PMID:18074008

How to Train a Cell - Cutting-Edge Molecular Tools

NASA Astrophysics Data System (ADS)

Czapiński, Jakub; Kiełbus, Michał; Kałafut, Joanna; Kos, Michał; Stepulak, Andrzej; Rivero-Müller, Adolfo

2017-03-01

In biological systems, the formation of molecular complexes is the currency for all cellular processes. Traditionally, functional experimentation was targeted to single molecular players in order to understand its effects in a cell or animal phenotype. In the last few years, we have been experiencing rapid progress in the development of ground-breaking molecular biology tools that affect the metabolic, structural, morphological, and (epi)genetic instructions of cells by chemical, optical (optogenetic) and mechanical inputs. Such precise dissection of cellular processes is not only essential for a better understanding of biological systems, but will also allow us to better diagnose and fix common dysfunctions. Here, we present several of these emerging and innovative techniques by providing the reader with elegant examples on how these tools have been implemented in cells, and, in some cases, organisms, to unravel molecular processes in minute detail. We also discuss their advantages and disadvantages with particular focus on their translation to multicellular organisms for in vivo spatiotemporal regulation. We envision that further developments of these tools will not only help solve the processes of life, but will give rise to novel clinical and industrial applications.

Nitric oxide, a double edged sword in cancer biology: searching for therapeutic opportunities.

PubMed

Mocellin, Simone; Bronte, Vincenzo; Nitti, Donato

2007-05-01

Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological and pathological processes. The last decade has witnessed major advances in dissecting NO biology and its role in cancer pathogenesis. However, the complexity of the interactions between different levels of NO and several aspects of tumor development/progression has led to apparently conflicting findings. Furthermore, both anti-NO and NO-based anticancer strategies appear effective in several preclinical models. This paradoxical dichotomy is leaving investigators with a double challenge: to determine the net impact of NO on cancer behavior and to define the therapeutic role of NO-centered anticancer strategies. Only a comprehensive and dynamic view of the cascade of molecular and cellular events underlying tumor biology and affected by NO will allow investigators to exploit the potential antitumor properties of drugs interfering with NO metabolism. Available data suggest that NO should be considered neither a universal target nor a magic bullet, but rather a signal transducer to be modulated according to the molecular makeup of each individual cancer and the interplay with conventional antineoplastic agents. (c) 2006 Wiley Periodicals, Inc.

The Influence of Perceived Disgust on Students' Motivation and Achievement

NASA Astrophysics Data System (ADS)

Randler, Christoph; Hummel, Eberhard; Wüst-Ackermann, Peter

2013-11-01

There are a wide range of student emotions in academic settings, but apart from emotions such as interest and well-being, disgust is a negative emotion which might be relevant in biology education, for instance, during dissection or when encountering living animals. This paper addresses the issue of situational disgust during a course at the university using living animals and prepared mounts. The course covers a wide range of organisms from protists (e.g. Paramecium) through invertebrates to vertebrates and uses many methods (e.g. microscopy, dissection, and behavioral observations) and specific content (anatomy, structure, and behavior). The dissection of the trout was rated as most disgusting, followed by working with living woodlice, living earthworms, and living snails. The least disgusting lessons were those dealing with microscopy, mammalian skulls, honeybee dance, and bird flight. Based on animals, macro-invertebrates were rated as most disgusting and mammals as least disgusting. Concerning methods, observing through a microscope was perceived as being least disgusting, followed by experiments without animals, then followed by experiments with living animals and, most disgusting, dissection. Disgust was correlated negatively with interest, well-being, and competence but positively with pressure and boredom. Thus, low disgust is related to high interest, well-being, and competence, while higher disgust is related to higher pressure and boredom. The results show a need for measuring situational disgust in addition to survey studies. They also suggest that perceived disgust negatively affects intrinsic motivation. This has implications for biology teaching, because carrying out dissections or experiencing living animals in the classroom may have a detrimental effect on motivation.

Pregnancy with aortic dissection in Ehler-Danlos syndrome. Staged replacement of the total aorta (10-year follow-up).

PubMed

Babatasi, G; Massetti, M; Bhoyroo, S; Khayat, A

1997-10-01

Pregnancy complicated by aortic dissection in patients with hereditary disorder of connective tissue presents interesting considerations including management of caesarean section with the unexpected need for cardiac surgery in emergency. Generalizations can be made on management principles with long-term follow-up requiring an aggressive individualized approach by a multidisciplinary team. A 33-year-old parturient presenting an aortic dissection at 37 weeks gestation required prompt diagnosis of Ehlers-Danlos syndrome in combination with correct surgical therapy resulted in the survival of both the mother and infant. During the 10-year follow-up, multiple complex dissection required transverse aortic arch and thoracoabdominal aortic replacement.

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

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

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We havemore » applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. Furthermore, a more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.« less

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing

DOE PAGES

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette; ...

2017-01-17

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We havemore » applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. Furthermore, a more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.« less

Network-based integration of systems genetics data reveals pathways associated with lignocellulosic biomass accumulation and processing.

PubMed

Mizrachi, Eshchar; Verbeke, Lieven; Christie, Nanette; Fierro, Ana C; Mansfield, Shawn D; Davis, Mark F; Gjersing, Erica; Tuskan, Gerald A; Van Montagu, Marc; Van de Peer, Yves; Marchal, Kathleen; Myburg, Alexander A

2017-01-31

As a consequence of their remarkable adaptability, fast growth, and superior wood properties, eucalypt tree plantations have emerged as key renewable feedstocks (over 20 million ha globally) for the production of pulp, paper, bioenergy, and other lignocellulosic products. However, most biomass properties such as growth, wood density, and wood chemistry are complex traits that are hard to improve in long-lived perennials. Systems genetics, a process of harnessing multiple levels of component trait information (e.g., transcript, protein, and metabolite variation) in populations that vary in complex traits, has proven effective for dissecting the genetics and biology of such traits. We have applied a network-based data integration (NBDI) method for a systems-level analysis of genes, processes and pathways underlying biomass and bioenergy-related traits using a segregating Eucalyptus hybrid population. We show that the integrative approach can link biologically meaningful sets of genes to complex traits and at the same time reveal the molecular basis of trait variation. Gene sets identified for related woody biomass traits were found to share regulatory loci, cluster in network neighborhoods, and exhibit enrichment for molecular functions such as xylan metabolism and cell wall development. These findings offer a framework for identifying the molecular underpinnings of complex biomass and bioprocessing-related traits. A more thorough understanding of the molecular basis of plant biomass traits should provide additional opportunities for the establishment of a sustainable bio-based economy.

Measuring Medical Students' Motivation to Learning Anatomy by Cadaveric Dissection

ERIC Educational Resources Information Center

Abdel Meguid, Eiman M.; Khalil, Mohammed K.

2017-01-01

Motivation and learning are inter-related. It is well known that motivating learners is clearly a complex endeavor, which can be influenced by the educational program and the learning environment. Limited research has been conducted to examine students' motivation as a method to assess the effectiveness of dissection in medical education. This…

Supportive techniques and devices for endoscopic submucosal dissection of gastric cancer.

PubMed

Sakurazawa, Nobuyuki; Kato, Shunji; Fujita, Itsuo; Kanazawa, Yoshikazu; Onodera, Hiroyuki; Uchida, Eiji

2012-06-16

The indications for endoscopic treatment have expanded in recent years, and relatively intestinal-type mucosal stomach carcinomas with a low potential for metastasis are now often resected en bloc by endoscopic submucosal dissection (ESD), even if they measure over 20 mm in size. However, ESD requires complex maneuvers, which entails a long operation time, and is often accompanied by complications such as bleeding and perforation. Many technical developments have been implemented to overcome these complications. The scope, cutting device, hemostasis device, and other supportive devices have been improved. However, even with these innovations, ESD remains a potentially complex procedure. One of the major difficulties is poor visualization of the submucosal layer resulting from the poor countertraction afforded during submucosal dissection. Recently, countertraction devices have been developed. In this paper, we introduce countertraction techniques and devices mainly for gastric cancer.

The Inflammasome and Danger Molecule Signaling: At the Crossroads of Inflammation and Pathogen Persistence in the Oral Cavity

PubMed Central

Yilmaz, Özlem; Lee, Kyu Lim

2014-01-01

Inflammasomes are an oligomeric assembly of multiprotein complexes that activate the caspase-1-dependent maturation and the subsequent secretion of inflammatory interleukin-1β and interleukin-18 cytokines in response to a ‘danger signal’ in vertebrates. The assessment of their significance continues to grow rapidly as the complex biology of various chronic inflammatory conditions are better dissected. Increasing evidence links inflammasomes and host-derived small ‘danger molecule ATP’-signaling strongly with the modulation of the host immune response by microbial colonizers as well as potential altering of the microbiome structure and inter-microbial interactions in host. All of these factors eventually lead to the destructive chronic inflammatory disease state. In the oral cavity, a highly dynamic and multifaceted interplay takes place between the endogenous danger molecule signaling and colonizing microbes on the mucosal surfaces. This interaction may redirect the local microenvironment to favor the conversion of the resident microbiome towards pathogenicity. This review outlines the major components of the known inflammasome complexes/mechanisms and highlights their regulation, in particular, by oral microorganisms in relation to the periodontal disease pathology. Better characterizations of the cellular and molecular biology of the inflammasome will likely present important potential therapeutic targets in the treatment and prevention of periodontal disease as well as other debilitating chronic diseases. PMID:26252403

From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

PubMed

Vella, Danila; Zoppis, Italo; Mauri, Giancarlo; Mauri, Pierluigi; Di Silvestre, Dario

2017-12-01

The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.

Coordination of Cell Polarity, Mechanics and Fate in Tissue Self-organization.

PubMed

Kim, Esther Jeong Yoon; Korotkevich, Ekaterina; Hiiragi, Takashi

2018-07-01

Self-organization guides robust, spatiotemporally ordered formation of complex tissues and ultimately whole organisms. While products of gene expression serve as building blocks of living matter, how these interact to give rise to tissues of distinct patterns and function remains a central question in biology. Tissue self-organization relies on dynamic interactions between constituents spanning a range of spatiotemporal scales with tuneable chemical and mechanical parameters. This review highlights recent studies dissecting mechanisms of these interactions. We propose that feedback interactions between cell polarity, mechanics, and fate are a key principle underlying tissue self-organization. We also provide a glimpse into how such processes can be studied in future endeavors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Arabidopsis non-host resistance to powdery mildews.

PubMed

Lipka, Ulrike; Fuchs, Rene; Lipka, Volker

2008-08-01

Immunity of an entire plant species against all genetic variants of a particular parasite is referred to as non-host resistance. Although non-host resistance represents the most common and durable form of plant resistance in nature, it has thus far been poorly understood at the molecular level. Recently, novel model systems have established the first mechanistic insights. The genetic dissection of Arabidopsis non-host resistance to non-adapted biotrophic powdery mildew fungi provided evidence for functionally redundant but operationally distinct pre- and post-invasion immune responses. Conceptually, these complex and successive defence mechanisms explain the durable and robust nature of non-host resistance. Pathogen lifestyle and infection biology, ecological parameters and the evolutionary relationship of the interaction partners determine differences and commonalities in other model systems.

[Thoracic aortic dissection revealed by systemic cholesterol embolism].

PubMed

Braem, L; Paule, P; Héno, P; Morand, J J; Mafart, B; La Folie, T; Varlet, P; Mioulet, D; Fourcade, L

2006-10-01

Systemic cholesterol embolism is a rare complication of atherosclerosis, and has various presentations. Arterial catheterisms are a common cause. However, the association with an aortic dissection has been exceptionally reported. We report the observation of a 70 year-old man, with coronary artery disease, hypertension, diabetes and dyslipidemia. Six months before hospitalization, a coronary angioplasty was performed due to recurrent angina. The association of purpuric lesions on the feet, with acute renal failure confirmed cholesterol embolism syndrome. Transoesophageal echocardiography showed a dissection of the descending thoracic aorta associated with complex atheroma. The evolution was marked by the pulpar necrosis of a toe and by a worsening of the renal failure, requiring definitive hemodialysis. Further echographic control highlighted the rupture of the intimal veil of the dissection. Cholesterol embolism syndrome may reveal an aortic dissection in patients without thoracic symptoms. In such cases, transoesophageal echocardiography is a useful and non-invasive examination.

Development of next-generation mapping populations: Multi-parent Advanced Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) populations in peanut

USDA-ARS?s Scientific Manuscript database

Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) have been proposed and used in many crops to dissect complex traits or QTL. MAGIC allows for dissecting genomic structure, and for improving breeding populations by integrating multiple alleles from different parents. MAR...

The effects of computer simulation versus hands-on dissection and the placement of computer simulation within the learning cycle on student achievement and attitude

NASA Astrophysics Data System (ADS)

Hopkins, Kathryn Susan

The value of dissection as an instructional strategy has been debated, but not evidenced in research literature. The purpose of this study was to examine the efficacy of using computer simulated frog dissection as a substitute for traditional hands-on frog dissection and to examine the possible enhancement of achievement by combining the two strategies in a specific sequence. In this study, 134 biology students at two Central Texas schools were divided into the five following treatment groups: computer simulation of frog dissection, computer simulation before dissection, traditional hands-on frog dissection, dissection before computer simulation, and textual worksheet materials. The effects on achievement were evaluated by labeling 10 structures on three diagrams, identifying 11 pinned structures on a prosected frog, and answering 9 multiple-choice questions over the dissection process. Attitude was evaluated using a thirty item survey with a five-point Likert scale. The quasi-experimental design was pretest/post-test/post-test nonequivalent group for both control and experimental groups, a 2 x 2 x 5 completely randomized factorial design (gender, school, five treatments). The pretest/post-test design was incorporated to control for prior knowledge using analysis of covariance. The dissection only group evidenced a significantly higher performance than all other treatments except dissection-then-computer on the post-test segment requiring students to label pinned anatomical parts on a prosected frog. Interactions between treatment and school in addition to interaction between treatment and gender were found to be significant. The diagram and attitude post-tests evidenced no significant difference. Results on the nine multiple-choice questions about dissection procedures indicated a significant difference between schools. The interaction between treatment and school was also found to be significant. On a delayed post-test, a significant difference in gender was found on the diagram labeling segment of the post-test. Males were reported to have the higher score. Since existing research conflicts with this study's results, additional research using authentic assessment is recommended. Instruction should be aligned with dissection content and process objectives for each treatment group, and the teacher variable should be controlled.

Functional annotation of the vlinc class of non-coding RNAs using systems biology approach

PubMed Central

Laurent, Georges St.; Vyatkin, Yuri; Antonets, Denis; Ri, Maxim; Qi, Yao; Saik, Olga; Shtokalo, Dmitry; de Hoon, Michiel J.L.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Arner, Erik; Forrest, Alistair R.R.; Nicolas, Estelle; McCaffrey, Timothy A.; Carninci, Piero; Hayashizaki, Yoshihide; Wahlestedt, Claes; Kapranov, Philipp

2016-01-01

Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlincRNAs genes likely function in cis to activate nearby genes. This effect while most pronounced in closely spaced vlincRNA–gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlincRNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs. PMID:27001520

Dissecting the function of Cullin-RING ubiquitin ligase complex genes in planarian regeneration.

PubMed

Strand, Nicholas S; Allen, John M; Ghulam, Mahjoobah; Taylor, Matthew R; Munday, Roma K; Carrillo, Melissa; Movsesyan, Artem; Zayas, Ricardo M

2018-01-15

The ubiquitin system plays a role in nearly every aspect of eukaryotic cell biology. The enzymes responsible for transferring ubiquitin onto specific substrates are the E3 ubiquitin ligases, a large and diverse family of proteins, for which biological roles and target substrates remain largely undefined. Studies using model organisms indicate that ubiquitin signaling mediates key steps in developmental processes and tissue regeneration. Here, we used the freshwater planarian, Schmidtea mediterranea, to investigate the role of Cullin-RING ubiquitin ligase (CRL) complexes in stem cell regulation during regeneration. We identified six S. mediterranea cullin genes, and used RNAi to uncover roles for homologs of Cullin-1, -3 and -4 in planarian regeneration. The cullin-1 RNAi phenotype included defects in blastema formation, organ regeneration, lesions, and lysis. To further investigate the function of cullin-1-mediated cellular processes in planarians, we examined genes encoding the adaptor protein Skp1 and F-box substrate-recognition proteins that are predicted to partner with Cullin-1. RNAi against skp1 resulted in phenotypes similar to cullin-1 RNAi, and an RNAi screen of the F-box genes identified 19 genes that recapitulated aspects of cullin-1 RNAi, including ones that in mammals are involved in stem cell regulation and cancer biology. Our data provides evidence that CRLs play discrete roles in regenerative processes and provide a platform to investigate how CRLs regulate stem cells in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Dissecting the hypothalamic pathways that underlie innate behaviors.

PubMed

Zha, Xi; Xu, Xiaohong

2015-12-01

Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.

Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†.

PubMed

Kirsten, Holger; Al-Hasani, Hoor; Holdt, Lesca; Gross, Arnd; Beutner, Frank; Krohn, Knut; Horn, Katrin; Ahnert, Peter; Burkhardt, Ralph; Reiche, Kristin; Hackermüller, Jörg; Löffler, Markus; Teupser, Daniel; Thiery, Joachim; Scholz, Markus

2015-08-15

Genetics of gene expression (eQTLs or expression QTLs) has proved an indispensable tool for understanding biological pathways and pathomechanisms of trait-associated SNPs. However, power of most genome-wide eQTL studies is still limited. We performed a large eQTL study in peripheral blood mononuclear cells of 2112 individuals increasing the power to detect trans-effects genome-wide. Going beyond univariate SNP-transcript associations, we analyse relations of eQTLs to biological pathways, polygenetic effects of expression regulation, trans-clusters and enrichment of co-localized functional elements. We found eQTLs for about 85% of analysed genes, and 18% of genes were trans-regulated. Local eSNPs were enriched up to a distance of 5 Mb to the transcript challenging typically implemented ranges of cis-regulations. Pathway enrichment within regulated genes of GWAS-related eSNPs supported functional relevance of identified eQTLs. We demonstrate that nearest genes of GWAS-SNPs might frequently be misleading functional candidates. We identified novel trans-clusters of potential functional relevance for GWAS-SNPs of several phenotypes including obesity-related traits, HDL-cholesterol levels and haematological phenotypes. We used chromatin immunoprecipitation data for demonstrating biological effects. Yet, we show for strongly heritable transcripts that still little trans-chromosomal heritability is explained by all identified trans-eSNPs; however, our data suggest that most cis-heritability of these transcripts seems explained. Dissection of co-localized functional elements indicated a prominent role of SNPs in loci of pseudogenes and non-coding RNAs for the regulation of coding genes. In summary, our study substantially increases the catalogue of human eQTLs and improves our understanding of the complex genetic regulation of gene expression, pathways and disease-related processes. © The Author 2015. Published by Oxford University Press.

Cross-study projections of genomic biomarkers: an evaluation in cancer genomics.

PubMed

Lucas, Joseph E; Carvalho, Carlos M; Chen, Julia Ling-Yu; Chi, Jen-Tsan; West, Mike

2009-01-01

Human disease studies using DNA microarrays in both clinical/observational and experimental/controlled studies are having increasing impact on our understanding of the complexity of human diseases. A fundamental concept is the use of gene expression as a "common currency" that links the results of in vitro controlled experiments to in vivo observational human studies. Many studies--in cancer and other diseases--have shown promise in using in vitro cell manipulations to improve understanding of in vivo biology, but experiments often simply fail to reflect the enormous phenotypic variation seen in human diseases. We address this with a framework and methods to dissect, enhance and extend the in vivo utility of in vitro derived gene expression signatures. From an experimentally defined gene expression signature we use statistical factor analysis to generate multiple quantitative factors in human cancer gene expression data. These factors retain their relationship to the original, one-dimensional in vitro signature but better describe the diversity of in vivo biology. In a breast cancer analysis, we show that factors can reflect fundamentally different biological processes linked to molecular and clinical features of human cancers, and that in combination they can improve prediction of clinical outcomes.

How to Train a Cell–Cutting-Edge Molecular Tools

PubMed Central

Czapiński, Jakub; Kiełbus, Michał; Kałafut, Joanna; Kos, Michał; Stepulak, Andrzej; Rivero-Müller, Adolfo

2017-01-01

In biological systems, the formation of molecular complexes is the currency for all cellular processes. Traditionally, functional experimentation was targeted to single molecular players in order to understand its effects in a cell or animal phenotype. In the last few years, we have been experiencing rapid progress in the development of ground-breaking molecular biology tools that affect the metabolic, structural, morphological, and (epi)genetic instructions of cells by chemical, optical (optogenetic) and mechanical inputs. Such precise dissection of cellular processes is not only essential for a better understanding of biological systems, but will also allow us to better diagnose and fix common dysfunctions. Here, we present several of these emerging and innovative techniques by providing the reader with elegant examples on how these tools have been implemented in cells, and, in some cases, organisms, to unravel molecular processes in minute detail. We also discuss their advantages and disadvantages with particular focus on their translation to multicellular organisms for in vivo spatiotemporal regulation. We envision that further developments of these tools will not only help solve the processes of life, but will give rise to novel clinical and industrial applications. PMID:28344971

Novel Insights into Tree Biology and Genome Evolution as Revealed Through Genomics.

PubMed

Neale, David B; Martínez-García, Pedro J; De La Torre, Amanda R; Montanari, Sara; Wei, Xiao-Xin

2017-04-28

Reference genome sequences are the key to the discovery of genes and gene families that determine traits of interest. Recent progress in sequencing technologies has enabled a rapid increase in genome sequencing of tree species, allowing the dissection of complex characters of economic importance, such as fruit and wood quality and resistance to biotic and abiotic stresses. Although the number of reference genome sequences for trees lags behind those for other plant species, it is not too early to gain insight into the unique features that distinguish trees from nontree plants. Our review of the published data suggests that, although many gene families are conserved among herbaceous and tree species, some gene families, such as those involved in resistance to biotic and abiotic stresses and in the synthesis and transport of sugars, are often expanded in tree genomes. As the genomes of more tree species are sequenced, comparative genomics will further elucidate the complexity of tree genomes and how this relates to traits unique to trees.

Microfluidic-based mini-metagenomics enables discovery of novel microbial lineages from complex environmental samples.

PubMed

Yu, Feiqiao Brian; Blainey, Paul C; Schulz, Frederik; Woyke, Tanja; Horowitz, Mark A; Quake, Stephen R

2017-07-05

Metagenomics and single-cell genomics have enabled genome discovery from unknown branches of life. However, extracting novel genomes from complex mixtures of metagenomic data can still be challenging and represents an ill-posed problem which is generally approached with ad hoc methods. Here we present a microfluidic-based mini-metagenomic method which offers a statistically rigorous approach to extract novel microbial genomes while preserving single-cell resolution. We used this approach to analyze two hot spring samples from Yellowstone National Park and extracted 29 new genomes, including three deeply branching lineages. The single-cell resolution enabled accurate quantification of genome function and abundance, down to 1% in relative abundance. Our analyses of genome level SNP distributions also revealed low to moderate environmental selection. The scale, resolution, and statistical power of microfluidic-based mini-metagenomics make it a powerful tool to dissect the genomic structure of microbial communities while effectively preserving the fundamental unit of biology, the single cell.

In Vitro Formation of Plant RNA-Induced Silencing Complexes Using an Extract of Evacuolated Tobacco Protoplasts.

PubMed

Iki, Taichiro; Ishikawa, Masayuki; Yoshikawa, Manabu

2017-01-01

Small RNA-mediated gene silencing is involved in a variety of biological processes among many eukaryotic organisms. The silencing effector, generally referred to as RNA-induced silencing complex (RISC), comprises an ARGONAUTE (AGO) protein and a small single-stranded guide RNA in its core. RISCs recognize target genes containing sequences complementary to the guide RNA and repress their expression transcriptionally or posttranscriptionally. In vitro systems that recapitulate RISC assembly are useful not only to decipher the molecular mechanisms underlying the assembly process itself but also to dissect the downstream silencing pathways mediated by RISCs. Here, we describe a method for in vitro plant RISC assembly, which relies on an extract of evacuolated protoplasts derived from Nicotiana tabacum BY-2 suspension-cultured cells. In this extract, synthetic duplexes of small RNAs are incorporated into AGO proteins that are synthesized by in vitro translation, and then duplex unwinding and selective strand elimination result in formation of mature RISCs.

DTWscore: differential expression and cell clustering analysis for time-series single-cell RNA-seq data.

PubMed

Wang, Zhuo; Jin, Shuilin; Liu, Guiyou; Zhang, Xiurui; Wang, Nan; Wu, Deliang; Hu, Yang; Zhang, Chiping; Jiang, Qinghua; Xu, Li; Wang, Yadong

2017-05-23

The development of single-cell RNA sequencing has enabled profound discoveries in biology, ranging from the dissection of the composition of complex tissues to the identification of novel cell types and dynamics in some specialized cellular environments. However, the large-scale generation of single-cell RNA-seq (scRNA-seq) data collected at multiple time points remains a challenge to effective measurement gene expression patterns in transcriptome analysis. We present an algorithm based on the Dynamic Time Warping score (DTWscore) combined with time-series data, that enables the detection of gene expression changes across scRNA-seq samples and recovery of potential cell types from complex mixtures of multiple cell types. The DTWscore successfully classify cells of different types with the most highly variable genes from time-series scRNA-seq data. The study was confined to methods that are implemented and available within the R framework. Sample datasets and R packages are available at https://github.com/xiaoxiaoxier/DTWscore .

[Biological characteristics and management of familial papillary thyroid carcinoma].

PubMed

Zhao, Jing; Yu, Yang; Xia, Ting-ting; Liu, You-zhong; Wei, Song-feng; Zheng, Xiang-qian; Gao, Ming

2011-11-01

To analyze the clinical biological characteristics and investigate the managements of familial papillary thyroid carcinoma (FPTC). Clinical data of 36 patients with PTC from 15 families were retrospectively analyzed compared with 95 control cases taken randomly from the patients with sporadic PTC diagnosed and treated in Tianjin Cancer Hospital between January 2010 and August 2011. Of the 36 patients with FPTC, 15 (41.7%) were ≥45 years old, 12 (33.3%) had bilateral carcinoma, 20 (55.6%) were multifocality, 27 (75.0%) had neck lymph node metastases, 17 (47.2%) coexisted thyroid benign tumors. Of the 95 patients with SPTC, 60 (63.2%) were ≥45 years old, 12(12.6%)had bilateral carcinomas, 21 (22.1%) were multifocality, 51 (53.7%) had neck lymph node metastases, and 26(27.4%)coexisted thyroid benign tumors. Of the 36 patients with FPTC, 22 (61.1%) underwent total thyroidectomy and 14 (38.9%) with unilateral thyroidectomy plus isthmusectomy, 3 (8.3%) received unilateral or bilateral lateral neck dissection and central compartment neck dissection (CND), 7 (19.4%) received unilateral or bilateral posterolateral neck dissection and CND, 6 (16.6%) received posterolateral neck dissection and bilateral CND, and 20 (55.6%) received unilateral or bilateral CND. Age at disease presentation of FPTC was younger than that of SPTC. FPTC has higher rates of multifocality and bilateral carcinoma coexisting with thyroid benign tumor than those of SPTC. It necessary to take family history in detail and to evaluate diseases before operation.

The Responsible Use of Animals in Biology Classrooms Including Alternatives to Dissection. Monograph IV.

ERIC Educational Resources Information Center

Hairston, Rosalina V., Ed.

This monograph discusses the care and maintenance of animals, suggests some alternative teaching strategies, and affirms the value of teaching biology as the study of living organisms, rather than dead specimens. The lessons in this monograph are intended as guidelines that teachers should adapt for their own particular classroom needs. Chapter 1,…

DISSECT: a new mnemonic-based approach to the categorization of aortic dissection.

PubMed

Dake, M D; Thompson, M; van Sambeek, M; Vermassen, F; Morales, J P

2013-08-01

Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic entity. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making. The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of six critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The six features of aortic dissection include: duration of disease; intimal tear location; size of the dissected aorta; segmental extent of aortic involvement; clinical complications of the dissection, and thrombus within the aortic false lumen. In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair in select cases of type B aortic dissection. Currently, endovascular aortic repair is not used for patients with type A aortic dissection, but catheter-based techniques directed at peripheral branch vessel ischemia that may complicate type A dissection are considered valuable adjunctive interventions, when indicated. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised more than 40 years ago, before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease process. Copyright © 2013 European Society for Vascular Surgery. All rights reserved.

Dissecting the actin cortex density and membrane-cortex distance in living cells by super-resolution microscopy

NASA Astrophysics Data System (ADS)

Clausen, M. P.; Colin-York, H.; Schneider, F.; Eggeling, C.; Fritzsche, M.

2017-02-01

Nanoscale spacing between the plasma membrane and the underlying cortical actin cytoskeleton profoundly modulates cellular morphology, mechanics, and function. Measuring this distance has been a key challenge in cell biology. Current methods for dissecting the nanoscale spacing either limit themselves to complex survey design using fixed samples or rely on diffraction-limited fluorescence imaging whose spatial resolution is insufficient to quantify distances on the nanoscale. Using dual-color super-resolution STED (stimulated-emission-depletion) microscopy, we here overcome this challenge and accurately measure the density distribution of the cortical actin cytoskeleton and the distance between the actin cortex and the membrane in live Jurkat T-cells. We found an asymmetric cortical actin density distribution with a mean width of 230 (+105/-125) nm. The spatial distances measured between the maximum density peaks of the cortex and the membrane were bi-modally distributed with mean values of 50  ±  15 nm and 120  ±  40 nm, respectively. Taken together with the finite width of the cortex, our results suggest that in some regions the cortical actin is closer than 10 nm to the membrane and a maximum of 20 nm in others.

Femtosecond laser dissection in C. elegans neural circuits

NASA Astrophysics Data System (ADS)

Samuel, Aravinthan D. T.; Chung, Samuel H.; Clark, Damon A.; Gabel, Christopher V.; Chang, Chieh; Murthy, Venkatesh; Mazur, Eric

2006-02-01

The nematode C. elegans, a millimeter-long roundworm, is a well-established model organism for studies of neural development and behavior, however physiological methods to manipulate and monitor the activity of its neural network have lagged behind the development of powerful methods in genetics and molecular biology. The small size and transparency of C. elegans make the worm an ideal test-bed for the development of physiological methods derived from optics and microscopy. We present the development and application of a new physiological tool: femtosecond laser dissection, which allows us to selectively ablate segments of individual neural fibers within live C. elegans. Femtosecond laser dissection provides a scalpel with submicrometer resolution, and we discuss its application in studies of neural growth, regenerative growth, and the neural basis of behavior.

Context Specificity of Stress-activated Mitogen-activated Protein (MAP) Kinase Signaling: The Story as Told by Caenorhabditis elegans*

PubMed Central

Andrusiak, Matthew G.; Jin, Yishi

2016-01-01

Stress-associated p38 and JNK mitogen-activated protein (MAP) kinase signaling cascades trigger specific cellular responses and are involved in multiple disease states. At the root of MAP kinase signaling complexity is the differential use of common components on a context-specific basis. The roundworm Caenorhabditis elegans was developed as a system to study genes required for development and nervous system function. The powerful genetics of C. elegans in combination with molecular and cellular dissections has led to a greater understanding of how p38 and JNK signaling affects many biological processes under normal and stress conditions. This review focuses on the studies revealing context specificity of different stress-activated MAPK components in C. elegans. PMID:26907690

Supermarket Marine Biology.

ERIC Educational Resources Information Center

Colby, Jennifer A.; And Others

1995-01-01

Describes a survey used to determine the availability of intact marine vertebrates and live invertebrates in supermarkets. Results shows that local supermarkets frequently provide a variety of intact marine organisms suitable for demonstrations, experiments, or dissections. (ZWH)

LLY-507, a cell-active, potent, and selective inhibitor of protein-lysine methyltransferase SMYD2

DOE PAGES

Nguyen, Hannah; Allali-Hassani, Abdellah; Antonysamy, Stephen; ...

2015-03-30

SMYD2 is a lysine methyltransferase that catalyzes the monomethylation of several protein substrates including p53. SMYD2 is overexpressed in a significant percentage of esophageal squamous primary carcinomas, and that overexpression correlates with poor patient survival. However, the mechanism(s) by which SMYD2 promotes oncogenesis is not understood. A small molecule probe for SMYD2 would allow for the pharmacological dissection of this biology. In this report, we disclose LLY-507, a cell-active, potent small molecule inhibitor of SMYD2. LLY-507 is >100-fold selective for SMYD2 over a broad range of methyltransferase and non-methyltransferase targets. A 1.63-Å resolution crystal structure of SMYD2 in complex withmore » LLY-507 shows the inhibitor binding in the substrate peptide binding pocket. LLY-507 is active in cells as measured by reduction of SMYD2-induced monomethylation of p53 Lys(370) at submicromolar concentrations. We used LLY-507 to further test other potential roles of SMYD2. Mass spectrometry-based proteomics showed that cellular global histone methylation levels were not significantly affected by SMYD2 inhibition with LLY-507, and subcellular fractionation studies indicate that SMYD2 is primarily cytoplasmic, suggesting that SMYD2 targets a very small subset of histones at specific chromatin loci and/or non-histone substrates. Breast and liver cancers were identified through in silico data mining as tumor types that display amplification and/or overexpression of SMYD2. LLY-507 inhibited the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner. As a result, these findings suggest that LLY-507 serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes.« less

LLY-507, a cell-active, potent, and selective inhibitor of protein-lysine methyltransferase SMYD2

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

Nguyen, Hannah; Allali-Hassani, Abdellah; Antonysamy, Stephen

SMYD2 is a lysine methyltransferase that catalyzes the monomethylation of several protein substrates including p53. SMYD2 is overexpressed in a significant percentage of esophageal squamous primary carcinomas, and that overexpression correlates with poor patient survival. However, the mechanism(s) by which SMYD2 promotes oncogenesis is not understood. A small molecule probe for SMYD2 would allow for the pharmacological dissection of this biology. In this report, we disclose LLY-507, a cell-active, potent small molecule inhibitor of SMYD2. LLY-507 is >100-fold selective for SMYD2 over a broad range of methyltransferase and non-methyltransferase targets. A 1.63-Å resolution crystal structure of SMYD2 in complex withmore » LLY-507 shows the inhibitor binding in the substrate peptide binding pocket. LLY-507 is active in cells as measured by reduction of SMYD2-induced monomethylation of p53 Lys(370) at submicromolar concentrations. We used LLY-507 to further test other potential roles of SMYD2. Mass spectrometry-based proteomics showed that cellular global histone methylation levels were not significantly affected by SMYD2 inhibition with LLY-507, and subcellular fractionation studies indicate that SMYD2 is primarily cytoplasmic, suggesting that SMYD2 targets a very small subset of histones at specific chromatin loci and/or non-histone substrates. Breast and liver cancers were identified through in silico data mining as tumor types that display amplification and/or overexpression of SMYD2. LLY-507 inhibited the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner. As a result, these findings suggest that LLY-507 serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes.« less

Biology and preliminary host range of Hydrotimetes natans Kolbe (Coleoptera:Curculionidae)a natural enemy candidate for biological control of Cabomba caroliniana Gray (Cabombaceae) in Australia

USDA-ARS?s Scientific Manuscript database

Cabomba caroliniana Gray (Cabombaceae), otherwise known as cabomba or water fanwort, is a submerged, rooted macrophyte with heavily dissected leaves that produces flowers that extend above the water’s surface. It has been disseminated around the world through the aquarium trade and has become a nox...

Resuscitating the Critical in the Biological Grotesque: Blood, Guts, Biomachismo in Science/Education and Human Guinea Pig Discourse

ERIC Educational Resources Information Center

Weinstein, Matthew; Broda, Matthew

2009-01-01

This article draws on Bakhtin and other cultural studies theorists to understand the role of the grotesque as a libratory moment in biology education. Four examples of texts and moments are analyzed: Sylvia Branzei's "Grossology" series of children's books about the grotesque, observations of a pig heart dissection, a standard high school…

COPS: Detecting Co-Occurrence and Spatial Arrangement of Transcription Factor Binding Motifs in Genome-Wide Datasets

PubMed Central

Lohmann, Ingrid

2012-01-01

In multi-cellular organisms, spatiotemporal activity of cis-regulatory DNA elements depends on their occupancy by different transcription factors (TFs). In recent years, genome-wide ChIP-on-Chip, ChIP-Seq and DamID assays have been extensively used to unravel the combinatorial interaction of TFs with cis-regulatory modules (CRMs) in the genome. Even though genome-wide binding profiles are increasingly becoming available for different TFs, single TF binding profiles are in most cases not sufficient for dissecting complex regulatory networks. Thus, potent computational tools detecting statistically significant and biologically relevant TF-motif co-occurrences in genome-wide datasets are essential for analyzing context-dependent transcriptional regulation. We have developed COPS (Co-Occurrence Pattern Search), a new bioinformatics tool based on a combination of association rules and Markov chain models, which detects co-occurring TF binding sites (BSs) on genomic regions of interest. COPS scans DNA sequences for frequent motif patterns using a Frequent-Pattern tree based data mining approach, which allows efficient performance of the software with respect to both data structure and implementation speed, in particular when mining large datasets. Since transcriptional gene regulation very often relies on the formation of regulatory protein complexes mediated by closely adjoining TF binding sites on CRMs, COPS additionally detects preferred short distance between co-occurring TF motifs. The performance of our software with respect to biological significance was evaluated using three published datasets containing genomic regions that are independently bound by several TFs involved in a defined biological process. In sum, COPS is a fast, efficient and user-friendly tool mining statistically and biologically significant TFBS co-occurrences and therefore allows the identification of TFs that combinatorially regulate gene expression. PMID:23272209

[Three-dimensional endoscopic endonasal study of skull base anatomy].

PubMed

Abarca-Olivas, Javier; Monjas-Cánovas, Irene; López-Álvarez, Beatriz; Lloret-García, Jaime; Sanchez-del Campo, Jose; Gras-Albert, Juan Ramon; Moreno-López, Pedro

2014-01-01

Training in dissection of the paranasal sinuses and the skull base is essential for anatomical understanding and correct surgical techniques. Three-dimensional (3D) visualisation of endoscopic skull base anatomy increases spatial orientation and allows depth perception. To show endoscopic skull base anatomy based on the 3D technique. We performed endoscopic dissection in cadaveric specimens fixed with formalin and with the Thiel technique, both prepared using intravascular injection of coloured material. Endonasal approaches were performed with conventional 2D endoscopes. Then we applied the 3D anaglyph technique to illustrate the pictures in 3D. The most important anatomical structures and landmarks of the sellar region under endonasal endoscopic vision are illustrated in 3D images. The skull base consists of complex bony and neurovascular structures. Experience with cadaver dissection is essential to understand complex anatomy and develop surgical skills. A 3D view constitutes a useful tool for understanding skull base anatomy. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response

PubMed Central

Adamson, Britt; Norman, Thomas M.; Jost, Marco; Cho, Min Y.; Nuñez, James K.; Chen, Yuwen; Villalta, Jacqueline E.; Gilbert, Luke A.; Horlbeck, Max A.; Hein, Marco Y.; Pak, Ryan A.; Gray, Andrew N.; Gross, Carol A.; Dixit, Atray; Parnas, Oren; Regev, Aviv; Weissman, Jonathan S.

2016-01-01

SUMMARY Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ~100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses. PMID:27984733

Measuring medical students' motivation to learning anatomy by cadaveric dissection.

PubMed

Abdel Meguid, Eiman M; Khalil, Mohammed K

2017-07-01

Motivation and learning are inter-related. It is well known that motivating learners is clearly a complex endeavor, which can be influenced by the educational program and the learning environment. Limited research has been conducted to examine students' motivation as a method to assess the effectiveness of dissection in medical education. This study aimed to assess and analyze students' motivation following their dissection experience. A 29-item survey was developed based on the Attention, Relevance, Confidence, and Satisfaction model of motivation. Descriptive statistics were undertaken to describe students' motivation to the dissection experience. T-test and ANOVA were used to compare differences in motivational scores between gender and educational characteristics of students. Dissection activities appear to promote students' motivation. Gender difference was statistically significant as males were more motivated by the dissection experience than females. Comparison between students with different knowledge of anatomy was also significantly different. The study is an important step in the motivational design to improve students' motivation to learn. The outcome of this study provides guidance to the selection of specific strategies to increase motivation by generating motivational strategies/tactics to facilitate learning. Anat Sci Educ 10: 363-371. © 2016 American Association of Anatomists. © 2016 American Association of Anatomists.

Laboratory Techniques for the Blind

ERIC Educational Resources Information Center

Tombaugh, Dorothy

1972-01-01

Describes modifications of laboratory procedures for the BSCS Green Version biology, including dissection, microbiology, animal behavior, physiology, biochemistry, and genetics that make the methods suitable for direct experimentation by blind students. Discusses models as substitutes for microscopy. (AL)

[Molecular Biology on the Mechanisms of Autism Spectrum Disorder for Clinical Psychiatrists].

PubMed

Makinodan, Manabu

2015-01-01

While, in general, a certain number of clinical psychiatrists might not be familiar with molecular biology, the mechanisms of mental illnesses have been uncovered by molecular biology for decades. Among mental illnesses, even biological psychiatrists and neuroscientists have paid less attention to the biological treatment of autism spectrum disorder (ASD) than Alzheimer's disease and schizophrenia since ASD has been regarded as a developmental disorder that was seemingly untreatable. However, multifaceted methods of molecular biology have revealed the mechanisms that would lead to the medication of ASD. In this article, how molecular biology dissects the pathobiology of ASD is described in order to announce the possibilities of biological treatment for clinical psychiatrists.

Integrated genomics and molecular breeding approaches for dissecting the complex quantitative traits in crop plants.

PubMed

Kujur, Alice; Saxena, Maneesha S; Bajaj, Deepak; Laxmi; Parida, Swarup K

2013-12-01

The enormous population growth, climate change and global warming are now considered major threats to agriculture and world's food security. To improve the productivity and sustainability of agriculture, the development of highyielding and durable abiotic and biotic stress-tolerant cultivars and/climate resilient crops is essential. Henceforth, understanding the molecular mechanism and dissection of complex quantitative yield and stress tolerance traits is the prime objective in current agricultural biotechnology research. In recent years, tremendous progress has been made in plant genomics and molecular breeding research pertaining to conventional and next-generation whole genome, transcriptome and epigenome sequencing efforts, generation of huge genomic, transcriptomic and epigenomic resources and development of modern genomics-assisted breeding approaches in diverse crop genotypes with contrasting yield and abiotic stress tolerance traits. Unfortunately, the detailed molecular mechanism and gene regulatory networks controlling such complex quantitative traits is not yet well understood in crop plants. Therefore, we propose an integrated strategies involving available enormous and diverse traditional and modern -omics (structural, functional, comparative and epigenomics) approaches/resources and genomics-assisted breeding methods which agricultural biotechnologist can adopt/utilize to dissect and decode the molecular and gene regulatory networks involved in the complex quantitative yield and stress tolerance traits in crop plants. This would provide clues and much needed inputs for rapid selection of novel functionally relevant molecular tags regulating such complex traits to expedite traditional and modern marker-assisted genetic enhancement studies in target crop species for developing high-yielding stress-tolerant varieties.

Using checklists in a gross anatomy laboratory improves learning outcomes and dissection quality.

PubMed

Hofer, Ryan Engebretson; Nikolaus, O Brant; Pawlina, Wojciech

2011-01-01

Checklists have been widely used in the aviation industry ever since aircraft operations became more complex than any single pilot could reasonably remember. More recently, checklists have found their way into medicine, where cognitive function can be compromised by stress and fatigue. The use of checklists in medical education has rarely been reported, especially in the basic sciences. We explored whether the use of a checklist in the gross anatomy laboratory would improve learning outcomes, dissection quality, and students' satisfaction in the first-year Human Structure didactic block at Mayo Medical School. During the second half of a seven-week anatomy course, dissection teams were each day given a hardcopy checklist of the structures to be identified during that day's dissection. The first half of the course was considered the control, as students did not receive any checklists to utilize during dissection. The measured outcomes were scored on four practice practical examinations and four dissection quality assessments, two each from the first half (control) and second half of the course. A student satisfaction survey was distributed at the end of the course. Examination and dissection scores were analyzed for correlations between practice practical examination score and checklist use. Our data suggest that a daily hardcopy list of anatomical structures for active use in the gross anatomy laboratory increases practice practical examination scores and dissection quality. Students recommend the use of these checklists in future anatomy courses. Copyright © 2011 American Association of Anatomists.

Genome-wide protein-protein interactions and protein function exploration in cyanobacteria

PubMed Central

Lv, Qi; Ma, Weimin; Liu, Hui; Li, Jiang; Wang, Huan; Lu, Fang; Zhao, Chen; Shi, Tieliu

2015-01-01

Genome-wide network analysis is well implemented to study proteins of unknown function. Here, we effectively explored protein functions and the biological mechanism based on inferred high confident protein-protein interaction (PPI) network in cyanobacteria. We integrated data from seven different sources and predicted 1,997 PPIs, which were evaluated by experiments in molecular mechanism, text mining of literatures in proved direct/indirect evidences, and “interologs” in conservation. Combined the predicted PPIs with known PPIs, we obtained 4,715 no-redundant PPIs (involving 3,231 proteins covering over 90% of genome) to generate the PPI network. Based on the PPI network, terms in Gene ontology (GO) were assigned to function-unknown proteins. Functional modules were identified by dissecting the PPI network into sub-networks and analyzing pathway enrichment, with which we investigated novel function of underlying proteins in protein complexes and pathways. Examples of photosynthesis and DNA repair indicate that the network approach is a powerful tool in protein function analysis. Overall, this systems biology approach provides a new insight into posterior functional analysis of PPIs in cyanobacteria. PMID:26490033

Systems Biology Approach to the Dissection of the Complexity of Regulatory Networks in the S. scrofa Cardiocirculatory System

PubMed Central

Martini, Paolo; Sales, Gabriele; Calura, Enrica; Brugiolo, Mattia; Lanfranchi, Gerolamo; Romualdi, Chiara; Cagnin, Stefano

2013-01-01

Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets. PMID:24284405

[Current topics on cancer biology and research strategies for anti-cancer traditional Chinese medicine].

PubMed

Chen, Xiu-ping; Tang, Zheng-hai; Shi, Zhe; Lu, Jin-jian; Su, Huan-xing; Chen, Xin; Wang, Yi-tao

2015-09-01

Cancer, an abnormal cell proliferation resulted from multi-factors,has the highest morbidity and mortality among all the serious diseases. Considerable progress has been made in cancer biology in recent years. Tumor immunology, cancer stem cells (CSCs), autophagy, and epithelial-mesenchymal transition (EMT) have become hot topics of interests in this area. Detailed dissection of these biological processes will provide novel directions, targets, and strategies for the pharmacological evaluation, mechanism elucidation, and new drug development of traditional Chinese medicine.

Path lumping: An efficient algorithm to identify metastable path channels for conformational dynamics of multi-body systems

NASA Astrophysics Data System (ADS)

Meng, Luming; Sheong, Fu Kit; Zeng, Xiangze; Zhu, Lizhe; Huang, Xuhui

2017-07-01

Constructing Markov state models from large-scale molecular dynamics simulation trajectories is a promising approach to dissect the kinetic mechanisms of complex chemical and biological processes. Combined with transition path theory, Markov state models can be applied to identify all pathways connecting any conformational states of interest. However, the identified pathways can be too complex to comprehend, especially for multi-body processes where numerous parallel pathways with comparable flux probability often coexist. Here, we have developed a path lumping method to group these parallel pathways into metastable path channels for analysis. We define the similarity between two pathways as the intercrossing flux between them and then apply the spectral clustering algorithm to lump these pathways into groups. We demonstrate the power of our method by applying it to two systems: a 2D-potential consisting of four metastable energy channels and the hydrophobic collapse process of two hydrophobic molecules. In both cases, our algorithm successfully reveals the metastable path channels. We expect this path lumping algorithm to be a promising tool for revealing unprecedented insights into the kinetic mechanisms of complex multi-body processes.

Functional annotation of the vlinc class of non-coding RNAs using systems biology approach.

PubMed

St Laurent, Georges; Vyatkin, Yuri; Antonets, Denis; Ri, Maxim; Qi, Yao; Saik, Olga; Shtokalo, Dmitry; de Hoon, Michiel J L; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Arner, Erik; Forrest, Alistair R R; Nicolas, Estelle; McCaffrey, Timothy A; Carninci, Piero; Hayashizaki, Yoshihide; Wahlestedt, Claes; Kapranov, Philipp

2016-04-20

Functionality of the non-coding transcripts encoded by the human genome is the coveted goal of the modern genomics research. While commonly relied on the classical methods of forward genetics, integration of different genomics datasets in a global Systems Biology fashion presents a more productive avenue of achieving this very complex aim. Here we report application of a Systems Biology-based approach to dissect functionality of a newly identified vast class of very long intergenic non-coding (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, we show that these RNAs could be grouped into 1542 novel human genes based on analysis of insulators that we show here indeed function as genomic barrier elements. We show that vlinc RNAs genes likely function in cisto activate nearby genes. This effect while most pronounced in closely spaced vlinc RNA-gene pairs can be detected over relatively large genomic distances. Furthermore, we identified 101 vlinc RNA genes likely involved in early embryogenesis based on patterns of their expression and regulation. We also found another 109 such genes potentially involved in cellular functions also happening at early stages of development such as proliferation, migration and apoptosis. Overall, we show that Systems Biology-based methods have great promise for functional annotation of non-coding RNAs. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

A quantum informational approach for dissecting chemical reactions

NASA Astrophysics Data System (ADS)

Duperrouzel, Corinne; Tecmer, Paweł; Boguslawski, Katharina; Barcza, Gergely; Legeza, Örs; Ayers, Paul W.

2015-02-01

We present a conceptionally different approach to dissect bond-formation processes in metal-driven catalysis using concepts from quantum information theory. Our method uses the entanglement and correlation among molecular orbitals to analyze changes in electronic structure that accompany chemical processes. As a proof-of-principle example, the evolution of nickel-ethene bond-formation is dissected, which allows us to monitor the interplay of back-bonding and π-donation along the reaction coordinate. Furthermore, the reaction pathway of nickel-ethene complexation is analyzed using quantum chemistry methods, revealing the presence of a transition state. Our study supports the crucial role of metal-to-ligand back-donation in the bond-forming process of nickel-ethene.

Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy*

PubMed Central

Turk, Rolf; Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Pospisil, Tyler C.; Jones, Kayla S.; Campbell, Kevin P.; Wright, Michael E.

2016-01-01

Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research. PMID:27099343

High-Throughput Dissection of AAV-Host Interactions: The Fast and the Curious.

PubMed

Herrmann, Anne-Kathrin; Grimm, Dirk

2018-05-18

Over fifty years after its initial description, Adeno-associated virus (AAV) remains a most exciting but also most elusive study object in basic or applied virology. On the one hand, its simple structure not only facilitates investigations into virus biology, but combined with the availability of numerous natural AAV variants with distinct infection efficiency and specificity also makes AAV a preferred substrate for engineering of gene delivery vectors. On the other hand, it is striking to witness a recent flurry of reports that highlight and partially close persistent gaps in our understanding of AAV virus and vector biology. This is all the more perplexing considering that recombinant AAVs have already been used in >160 clinical trials and recently been commercialized as gene therapeutics. Here, we discuss a reason for these advances in AAV research, namely, the advent and application of powerful high-throughput technology for dissection of AAV-host interactions and optimization of AAV gene therapy vectors. As relevant examples, we focus on the discovery of (i) a "new" cellular AAV receptor, AAVR, (ii) host restriction factors for AAV entry, and (iii) AAV capsid determinants that mediate trafficking through the blood-brain barrier. While (i)/(ii) are prototypes of extra- or intracellular AAV host factors that were identified via high-throughput screenings, (iii) exemplifies the power of molecular evolution to investigate the virus itself. In the future, we anticipate that these and other key technologies will continue to accelerate the dissection of AAV biology and will yield a wealth of new designer viruses for clinical use. Copyright © 2018. Published by Elsevier Ltd.

The structure and function of cell membranes examined by atomic force microscopy and single-molecule force spectroscopy.

PubMed

Shan, Yuping; Wang, Hongda

2015-06-07

The cell membrane is one of the most complicated biological complexes, and long-term fierce debates regarding the cell membrane persist because of technical hurdles. With the rapid development of nanotechnology and single-molecule techniques, our understanding of cell membranes has substantially increased. Atomic force microscopy (AFM) has provided several unprecedented advances (e.g., high resolution, three-dimensional and in situ measurements) in the study of cell membranes and has been used to systematically dissect the membrane structure in situ from both sides of membranes; as a result, novel models of cell membranes have recently been proposed. This review summarizes the new progress regarding membrane structure using in situ AFM and single-molecule force spectroscopy (SMFS), which may shed light on the study of the structure and functions of cell membranes.

Dissecting biological “dark matter” with single-cell genetic analysis of rare and uncultivated TM7 microbes from the human mouth

PubMed Central

Marcy, Yann; Ouverney, Cleber; Bik, Elisabeth M.; Lösekann, Tina; Ivanova, Natalia; Martin, Hector Garcia; Szeto, Ernest; Platt, Darren; Hugenholtz, Philip; Relman, David A.; Quake, Stephen R.

2007-01-01

We have developed a microfluidic device that allows the isolation and genome amplification of individual microbial cells, thereby enabling organism-level genomic analysis of complex microbial ecosystems without the need for culture. This device was used to perform a directed survey of the human subgingival crevice and to isolate bacteria having rod-like morphology. Several isolated microbes had a 16S rRNA sequence that placed them in candidate phylum TM7, which has no cultivated or sequenced members. Genome amplification from individual TM7 cells allowed us to sequence and assemble >1,000 genes, providing insight into the physiology of members of this phylum. This approach enables single-cell genetic analysis of any uncultivated minority member of a microbial community. PMID:17620602

Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

PubMed

Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

2012-03-01

Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

One-year outcomes after successful chronic total occlusion percutaneous coronary intervention: The impact of dissection re-entry techniques.

PubMed

Wilson, W M; Walsh, S J; Bagnall, A; Yan, A T; Hanratty, C G; Egred, M; Smith, E; Oldroyd, K G; McEntegart, M; Irving, J; Douglas, H; Strange, J; Spratt, J C

2017-11-01

We aimed to determine clinical outcomes 1 year after successful chronic total occlusion (CTO) PCI and, in particular, whether use of dissection and re-entry strategies affects clinical outcomes. Hybrid approaches have increased the procedural success of CTO percutaneous coronary intervention (PCI) but longer-term outcomes are unknown, particularly in relation to dissection and re-entry techniques. Data were collected for consecutive CTO PCIs performed by hybrid-trained operators from 7 United Kingdom (UK) centres between 2012 and 2014. The primary endpoint (death, myocardial infarction, unplanned target vessel revascularization) was measured at 12 months along with angina status. One-year follow up data were available for 96% of successful cases (n = 805). In total, 85% of patients had a CCS angina class of 2-4 prior to CTO PCI. Final successful procedural strategy was antegrade wire escalation 48%; antegrade dissection and re-entry (ADR) 21%; retrograde wire escalation 5%; retrograde dissection and re-entry (RDR) 26%. Overall, 47% of CTOs were recanalized using dissection and re-entry strategies. During a mean follow up of 11.5 ± 3.8 months, the primary endpoint occurred in 8.6% (n = 69) of patients (10.3% (n = 39/375) in DART group and 7.0% (n = 30/430) in wire-based cases). The majority of patients (88%) had no or minimal angina (CCS class 0 or 1). ADR and RDR were used more frequently in more complex cases with greater disease burden, however, the only independent predictor of the primary endpoint was lesion length. CTO PCI in complex lesions using the hybrid approach is safe, effective and has a low one-year adverse event rate. The method used to recanalize arteries was not associated with adverse outcomes. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Annual Research Review: Discovery science strategies in studies of the pathophysiology of child and adolescent psychiatric disorders--promises and limitations.

PubMed

Zhao, Yihong; Castellanos, F Xavier

2016-03-01

Psychiatric science remains descriptive, with a categorical nosology intended to enhance interobserver reliability. Increased awareness of the mismatch between categorical classifications and the complexity of biological systems drives the search for novel frameworks including discovery science in Big Data. In this review, we provide an overview of incipient approaches, primarily focused on classically categorical diagnoses such as schizophrenia (SZ), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD), but also reference convincing, if focal, advances in cancer biology, to describe the challenges of Big Data and discovery science, and outline approaches being formulated to overcome existing obstacles. A paradigm shift from categorical diagnoses to a domain/structure-based nosology and from linear causal chains to complex causal network models of brain-behavior relationship is ongoing. This (r)evolution involves appreciating the complexity, dimensionality, and heterogeneity of neuropsychiatric data collected from multiple sources ('broad' data) along with data obtained at multiple levels of analysis, ranging from genes to molecules, cells, circuits, and behaviors ('deep' data). Both of these types of Big Data landscapes require the use and development of robust and powerful informatics and statistical approaches. Thus, we describe Big Data analysis pipelines and the promise and potential limitations in using Big Data approaches to study psychiatric disorders. We highlight key resources available for psychopathological studies and call for the application and development of Big Data approaches to dissect the causes and mechanisms of neuropsychiatric disorders and identify corresponding biomarkers for early diagnosis. © 2016 Association for Child and Adolescent Mental Health.

Annual Research Review: Discovery science strategies in studies of the pathophysiology of child and adolescent psychiatric disorders: promises and limitations

PubMed Central

Zhao, Yihong; Castellanos, F. Xavier

2015-01-01

Background and Scope Psychiatric science remains descriptive, with a categorical nosology intended to enhance inter-observer reliability. Increased awareness of the mismatch between categorical classifications and the complexity of biological systems drives the search for novel frameworks including discovery science in Big Data. In this review, we provide an overview of incipient approaches, primarily focused on classically categorical diagnoses such as schizophrenia (SZ), autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but also reference convincing, if focal, advances in cancer biology, to describe the challenges of Big Data and discovery science, and outline approaches being formulated to overcome existing obstacles. Findings A paradigm shift from categorical diagnoses to a domain/structure-based nosology and from linear causal chains to complex causal network models of brain-behavior relationship is ongoing. This (r)evolution involves appreciating the complexity, dimensionality and heterogeneity of neuropsychiatric data collected from multiple sources (“broad” data) along with data obtained at multiple levels of analysis, ranging from genes to molecules, cells, circuits and behaviors (“deep” data). Both of these types of Big Data landscapes require the use and development of robust and powerful informatics and statistical approaches. Thus, we describe Big Data analysis pipelines and the promise and potential limitations in using Big Data approaches to study psychiatric disorders. Conclusion We highlight key resources available for psychopathological studies and call for the application and development of Big Data approaches to dissect the causes and mechanisms of neuropsychiatric disorders and identify corresponding biomarkers for early diagnosis. PMID:26732133

Genome Wide Association Mapping in Arabidopsis thaliana Identifies Novel Genes Involved in Linking Allyl Glucosinolate to Altered Biomass and Defense.

PubMed

Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A; Lin, Catherine; Kerwin, Rachel E; Burow, Meike; Kliebenstein, Daniel J

2016-01-01

A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis.

The paranasal sinuses: the last frontier in craniofacial biology.

PubMed

Márquez, Samuel

2008-11-01

This special issue of the Anatomical Record explores the presence and diversity of paranasal sinuses in distinct vertebrate groups. The following topics are addressed in particular: dinosaur physiology; development; physiology; adaptation; imaging; and primate systematics. A variety of approaches and techniques are used to examine and characterize the diversity of paranasal sinus pneumatization in a wide spectrum of vertebrates. These range from dissection to histology, from plain X-rays to computer tomography, from comparative anatomy to natural experimental settings, from mathematical computation to computer model simulation, and 2D to 3D reconstructions. The articles in this issue are a combination of literature review and new, hypothesis-driven anatomical research that highlights the complexities of paranasal sinus growth and development; ontogenetic and disease processes; physiology; paleontology; primate systematics; and human evolution. The issue incorporates a wide variety of vertebrates, encompassing a period of over 65 million years, in an effort to offer insight into the diversity of the paranasal sinus complexes through time and space, and thereby providing a greater understanding and appreciation of these special spaces within the cranium. Copyright 2008 Wiley-Liss, Inc.

Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase

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

Xiong, Yan; Li, Fengling; Babault, Nicolas

G9a-like protein (GLP) and G9a are highly homologous protein lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP and G9a form a heterodimer complex and catalyze mono- and dimethylation of histone H3 lysine 9 and nonhistone substrates. Although they are closely related, GLP and G9a possess distinct physiological and pathophysiological functions. Thus, GLP or G9a selective small-molecule inhibitors are useful tools to dissect their distinct biological functions. We previously reported potent and selective G9a/GLP dual inhibitors including UNC0638 and UNC0642. Here we report the discovery of potent and selective GLP inhibitors including 4 (MS0124) and 18more » (MS012), which are >30-fold and 140-fold selective for GLP over G9a and other methyltransferases, respectively. The cocrystal structures of GLP and G9a in the complex with either 4 or 18 displayed virtually identical binding modes and interactions, highlighting the challenges in structure-based design of selective inhibitors for either enzyme.« less

Microfluidic-based mini-metagenomics enables discovery of novel microbial lineages from complex environmental samples

PubMed Central

Yu, Feiqiao Brian; Blainey, Paul C; Schulz, Frederik; Woyke, Tanja; Horowitz, Mark A; Quake, Stephen R

2017-01-01

Metagenomics and single-cell genomics have enabled genome discovery from unknown branches of life. However, extracting novel genomes from complex mixtures of metagenomic data can still be challenging and represents an ill-posed problem which is generally approached with ad hoc methods. Here we present a microfluidic-based mini-metagenomic method which offers a statistically rigorous approach to extract novel microbial genomes while preserving single-cell resolution. We used this approach to analyze two hot spring samples from Yellowstone National Park and extracted 29 new genomes, including three deeply branching lineages. The single-cell resolution enabled accurate quantification of genome function and abundance, down to 1% in relative abundance. Our analyses of genome level SNP distributions also revealed low to moderate environmental selection. The scale, resolution, and statistical power of microfluidic-based mini-metagenomics make it a powerful tool to dissect the genomic structure of microbial communities while effectively preserving the fundamental unit of biology, the single cell. DOI: http://dx.doi.org/10.7554/eLife.26580.001 PMID:28678007

Parallel evolution of Nitric Oxide signaling: Diversity of synthesis & memory pathways

PubMed Central

Moroz, Leonid L.; Kohn, Andrea B.

2014-01-01

The origin of NO signaling can be traceable back to the origin of life with the large scale of parallel evolution of NO synthases (NOSs). Inducible-like NOSs may be the most basal prototype of all NOSs and that neuronal-like NOS might have evolved several times from this prototype. Other enzymatic and non-enzymatic pathways for NO synthesis have been discovered using reduction of nitrites, an alternative source of NO. Diverse synthetic mechanisms can co-exist within the same cell providing a complex NO-oxygen microenvironment tightly coupled with cellular energetics. The dissection of multiple sources of NO formation is crucial in analysis of complex biological processes such as neuronal integration and learning mechanisms when NO can act as a volume transmitter within memory-forming circuits. In particular, the molecular analysis of learning mechanisms (most notably in insects and gastropod molluscs) opens conceptually different perspectives to understand the logic of recruiting evolutionarily conserved pathways for novel functions. Giant uniquely identified cells from Aplysia and related species precent unuque opportunities for integrative analysis of NO signaling at the single cell level. PMID:21622160

Stable isotope probing to study functional components of complex microbial ecosystems.

PubMed

Mazard, Sophie; Schäfer, Hendrik

2014-01-01

This protocol presents a method of dissecting the DNA or RNA of key organisms involved in a specific biochemical process within a complex ecosystem. Stable isotope probing (SIP) allows the labelling and separation of nucleic acids from community members that are involved in important biochemical transformations, yet are often not the most numerically abundant members of a community. This pure culture-independent technique circumvents limitations of traditional microbial isolation techniques or data mining from large-scale whole-community metagenomic studies to tease out the identities and genomic repertoires of microorganisms participating in biological nutrient cycles. SIP experiments can be applied to virtually any ecosystem and biochemical pathway under investigation provided a suitable stable isotope substrate is available. This versatile methodology allows a wide range of analyses to be performed, from fatty-acid analyses, community structure and ecology studies, and targeted metagenomics involving nucleic acid sequencing. SIP experiments provide an effective alternative to large-scale whole-community metagenomic studies by specifically targeting the organisms or biochemical transformations of interest, thereby reducing the sequencing effort and time-consuming bioinformatics analyses of large datasets.

Dissecting genetic architecture of startle response in Drosophila melanogaster using multi-omics information.

PubMed

Xue, Angli; Wang, Hongcheng; Zhu, Jun

2017-09-28

Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

Treatment of Intra- and Extracranial Arterial Dissections Using Stents and Embolization

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

Joo, Jin Yang; Ahn, Jung Yong, E-mail: jyahn@cha.ac.kr; Chung, Young Sun

2005-06-15

Purpose. To evaluate the safety and efficacy of stent placement for extracranial and intracranial arterial dissections. Methods. Eighteen patients underwent endovascular treatment of carotid and vertebral dissections using intraluminal stent placement. Five patients with arterial dissection were treated, 2 using one insertion of a single stent and 3 using placement of two stents. Patients with a dissecting aneurysm were treated as follows: 7 patients with insertion of one stent, 4 with placement of two stents, and 2 by stent-assisted Guglielmi detachable coil embolization. In the 18 patients in whom stenting was attempted, the overall success in reaching the target lesionmore » was 94.4%. Of the 17 patients treated with stents, stent release and positioning were considered optimal in 16 (94%) and suboptimal in one (6%). In patients who underwent a successful procedure, all parent arteries were preserved. There were no instances of postprocedural ischemic attacks, new neurologic deficits, or new minor or major strokes prior to patient discharge. In follow up, all patients were assessed, using the modified Rankin scale, as functionally improved or of stable clinical status. The reduction in dissection-induced stenosis or pseudoaneurysm, the patency rate obtained at follow-up, and the lack of strokes (ischemic or hemorrhagic) suggest that stent placement offers a viable alternative to complex surgical bypass or reconstructive procedures. The long-term efficacy and durability of stent placement for arterial dissection remain to be determined in a larger series.« less

Preoperative Embolization of a Tumor-Bearing Horseshoe Kidney Via Both Channels of a Concomitant Aortic Dissection

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

Palmowski, Moritz; Kiessling, Fabian; Lopez-Benitez, Ruben

2007-06-15

Renal cell carcinoma arising in a horseshoe kidney is a rare entity. Preoperative tumor embolization can be performed to prevent massive bleeding complications during organ-preserving surgery. We report the first case of a patient with a tumor-bearing horseshoe-kidney in whom the preoperative embolization, already complex because of the abnormal vascular supply, was additionally complicated by an aortic dissection. An aberrant, horseshoe-kidney-supplying artery originated from the false dissection channel of the aorta, and thus had to be catheterized separately while the other tumor-supplying vessels could be reached via the true aortic lumen. After devascularization of the tumor, organ-preserving surgery was performedmore » without bleeding complications.« less

Anterior subcarinal node dissection on the left side using video thoracoscopy: an easier technique.

PubMed

Baste, Jean-Marc; Haddad, Laura; Melki, Jean; Peillon, Christophe

2015-04-01

Lobectomy for lung carcinoma is usually associated with complete node dissection, but it is often difficult to perform using video thoracoscopy, especially on the left side. In this case, our team uses an anterior technique for subcarinal lymphadenectomy. After left lobectomy, we lift the bronchial stump by its anterior face to open and dissect the subcarinal space. Exposure is difficult using the more usual technique of posterior subcarinal lymphadenectomy, and the different techniques (often requiring retractors) remain complex because some vessels might be injured. We recommend using anterior lymphadenectomy, which should facilitate video thoracoscopy for lymphadenectomy on the left side. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Dissecting Arabidopsis G beta signal transduction on the protein surface

USDA-ARS?s Scientific Manuscript database

The heterotrimeric G protein complex provides signal amplification and target specificity. The Arabidopsis Gbeta subunit of this complex (AGB1) interacts with and modulates the activity of target cytoplasmic proteins. This specificity resides in the structure of the interface between AGB1 and its ta...

A 2-microm continuous-wave laser system for safe and high-precision dissection during NOTES procedures.

PubMed

Dray, Xavier; Donatelli, Gianfranco; Krishnamurty, Devi Mukkai; Dubcenco, Elena; Wroblewski, Ronald J; Assumpcao, Lia; Giday, Samuel A; Buscaglia, Jonathan M; Shin, Eun J; Magno, Priscilla; Pipitone, Laurie J; Marohn, Michael R; Kantsevoy, Sergey V; Kalloo, Anthony N

2010-09-01

Lasers 2-microm in wavelength offer efficient tissue cutting with limited thermal damage in biological tissue. To evaluate the dissection capabilities of a 2-microm continuous-wave laser for NOTES procedures. We conducted 18 acute animal experiments. Group 1 (three animals): transcolonic access to the peritoneal cavity (15-W transcolonic laser puncture, balloon dilation over the laser probe). Group 2 (six animals): transcolonic access with needle-knife puncture and balloon dilation. Group 3 (three animals): transgastric access to the peritoneal cavity (similar technique as group 1) followed by laser-assisted dissection of the kidney. In one animal of group 3, a therapeutic target (hematoma) was created by percutaneous puncture of the kidney. Group 4 (six animals): transgastric access (similar to the technique of group 2). Translumenal access to the peritoneal cavity was achieved in 2-3 min in group 1 (significantly shorter than with the needle-knife-assisted technique, 4-5 min, p=0.02) and in 7-10 min in group 3 (compared to 6-17 min in group 4, p=0.88). In group 3, laser dissection of the parietal peritoneum and of perinephric connective tissue allowed access to the retroperitoneum with complete removal of a blood collection in the animal with puncture trauma. Laser dissection demonstrated good maneuverability, clean and rapid cutting, and excellent hemostasis. Peritoneoscopy and necropsy showed no damage of targeted tissue and surrounding organs. The 2-microm continuous-wave laser system showed promising capabilities for highly precise and safe dissection during NOTES procedures.

Coil embolization of an aneurysmal type B dissection persistent false lumen after visceral hybrid repair.

PubMed

Riga, Celia; Bicknell, Colin; Jenkins, Michael; Hamady, Mohamad

2009-01-01

Complex aortic dissections with subsequent dilatation may be managed by using a visceral hybrid approach. In some cases, however, there is substantial retrograde blood flow into the false lumen, leaving a pressurized aneurysmal segment. The authors describe a novel treatment method whereby successful seal of a distal type 1 endoleak was achieved with coil embolization and a liquid injectable embolic agent. The patient was followed up for 2 years without further aortic dilatation or complications.

[Detection of entomopathogen nematode [EPN - sand flies (Phlebotomus tobbi)] caught in the wild in Aydın, Kuşadası town and its assessment as a biological control agent].

PubMed

Karakuş, Mehmet; Arserim, Suha K; Töz, Seray Özensoy; Özbel, Yusuf

2013-01-01

In this study, the midgut of the sand flies investigated with direct method for the presence of parasites and other organisms. Wild sand flies collected in Kuşadası Town-Aydın, were dissected and midgut contents were examined by light microscopy. After midgut dissection, the head and genitalia of sand fly specimens were clarified and mounted for species identification. During the study, a total of 1027 sand flies were dissected. Eight and two species belonging to Phlebotomus and Sergentomyia genera were determined, respectively. Phlebotomus tobbi was found to be most abundant species (61.34%). A third stage of infective Entomopathogen Nematode belonging to Steinernematidae family was observed in the hemocoel of one specimen of P. tobbi during the dissection process. This is the first finding related to entomopathogen nematodes found in sand flies in Turkey. In the study, the sand fly fauna was determined in Kuşadası Town. For the control of sand flies, entomopathogenic nematodes which are not harmful for non-target organisms, can be used instead of chemical insecticides that can cause unknown damage in the environment.

Dissecting Impulsivity and its Relationships to Drug Addictions

PubMed Central

Ashenhurst, James R.; Cervantes, M. Catalina; James, Alexander S.; Groman, Stephanie M.; Pennington, Zachary T.

2015-01-01

Addictions are often characterized as forms of impulsive behavior. That said, it is often noted that impulsivity is a multidimensional construct, spanning several psychological domains. This review describes the relationship between varieties of impulsivity and addiction-related behaviors, the nature of the causal relationship between the two and the underlying neurobiological mechanisms that promote impulsive behaviors. We conclude that the available data strongly supports the notion that impulsivity is both a risk factor for, and a consequence of, drug and alcohol consumption. While the evidence indicating that subtypes of impulsive behavior are uniquely informative – either biologically or with respect to their relationships to addictions – is convincing, multiple lines of study link “distinct” subtypes of impulsivity to low dopamine D2 receptor function and perturbed serotonergic transmission, revealing shared mechanisms between the subtypes. Therefore, a common biological framework involving monoaminergic transmitters in key frontostriatal circuits may link multiple forms of impulsivity to drug self-administration and addiction-related behaviors. Further dissection of these relationships is needed before the next phase of genetic and genomic discovery will be able to reveal the biological sources of the vulnerability for addiction indexed by impulsivity. PMID:24654857

Germline Transgenic Methods for Tracking Cells and Testing Gene Function during Regeneration in the Axolotl

PubMed Central

Khattak, Shahryar; Schuez, Maritta; Richter, Tobias; Knapp, Dunja; Haigo, Saori L.; Sandoval-Guzmán, Tatiana; Hradlikova, Kristyna; Duemmler, Annett; Kerney, Ryan; Tanaka, Elly M.

2013-01-01

The salamander is the only tetrapod that regenerates complex body structures throughout life. Deciphering the underlying molecular processes of regeneration is fundamental for regenerative medicine and developmental biology, but the model organism had limited tools for molecular analysis. We describe a comprehensive set of germline transgenic strains in the laboratory-bred salamander Ambystoma mexicanum (axolotl) that open up the cellular and molecular genetic dissection of regeneration. We demonstrate tissue-dependent control of gene expression in nerve, Schwann cells, oligodendrocytes, muscle, epidermis, and cartilage. Furthermore, we demonstrate the use of tamoxifen-induced Cre/loxP-mediated recombination to indelibly mark different cell types. Finally, we inducibly overexpress the cell-cycle inhibitor p16INK4a, which negatively regulates spinal cord regeneration. These tissue-specific germline axolotl lines and tightly inducible Cre drivers and LoxP reporter lines render this classical regeneration model molecularly accessible. PMID:24052945

Perspective: Dendrimer drugs for infection and inflammation.

PubMed

Shaunak, Sunil

2015-12-18

Biologists are dissecting complex biological pathways at breath taking speed. It is opening up new opportunities for the therapeutic evaluation of novel dendrimer drugs. This review focuses on studies of small dendrimers decorated with sulfate, phosphonate, N-acetyl-cysteine, glucosamine and mannose in animal model studies of infection and inflammation. It highlights those animal model studies which have demonstrated the most promising dendrimer drug constructs as potential new medicines. The issues relating to their analytical chemistry that are slowing the progress of dendrimer drugs into the clinic are highlighted. It should be possible to solve these with additional analytical expertise because it is small dendrimers with only 16-32 peripheral groups that make for the best infection and inflammation related medicines. Public-private partnerships are now needed to progress these dendrimer drugs into proof-of-concept clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Multifunctional-layered materials for creating membrane-restricted nanodomains and nanoscale imaging

NASA Astrophysics Data System (ADS)

Srinivasan, P.

2016-01-01

Experimental platform that allows precise spatial positioning of biomolecules with an exquisite control at nanometer length scales is a valuable tool to study the molecular mechanisms of membrane bound signaling. Using micromachined thin film gold (Au) in layered architecture, it is possible to add both optical and biochemical functionalities in in vitro. Towards this goal, here, I show that docking of complementary DNA tethered giant phospholiposomes on Au surface can create membrane-restricted nanodomains. These nanodomains are critical features to dissect molecular choreography of membrane signaling complexes. The excited surface plasmon resonance modes of Au allow label-free imaging at diffraction-limited resolution of stably docked DNA tethered phospholiposomes, and lipid-detergent bicelle structures. Such multifunctional building block enables realizing rigorously controlled in vitro set-up to model membrane anchored biological signaling, besides serving as an optical tool for nanoscale imaging.

Isolation and in vitro binding of mating type plus fertilization tubules from Chlamydomonas.

PubMed

Wilson, Nedra F

2008-01-01

During fertilization in Chlamydomonas, adhesion and fusion of gametes occur at the tip of specialized regions of the plasma membrane, known as mating structures. The mating type minus (mt[-]) structure is a slightly raised dome-shaped region located at the apical end of the cell body. In contrast, the activated mating type plus (mt[+]) structure is an actin-filled, microvillouslike organelle. Interestingly, a similar type of "fusion organelle" is conserved across diverse groups. Chlamydomonas provides an ideal model system for studying the process of gametic cell fusion in that it is amenable to genetic manipulations as well as cell and molecular biological approaches. Moreover, the ease of culturing Chlamydomonas combined with the ability to isolate the mt(+) fertilization tubule and the development of in vitro assays for adhesion makes it an ideal system for biochemical studies focused on dissecting the molecular mechanisms that underlie the complex process of gametic cell fusion.

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

Sunden, Fanny; Peck, Ariana; Salzman, Julia

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modesmore » of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.« less

Virus-Based MicroRNA Silencing in Plants1[C][W][OPEN

PubMed Central

Sha, Aihua; Zhao, Jinping; Yin, Kangquan; Tang, Yang; Wang, Yan; Wei, Xiang; Hong, Yiguo; Liu, Yule

2014-01-01

MicroRNAs (miRNAs) play pivotal roles in various biological processes across kingdoms. Many plant miRNAs have been experimentally identified or predicted by bioinformatics mining of small RNA databases. However, the functions of these miRNAs remain largely unknown due to the lack of effective genetic tools. Here, we report a virus-based microRNA silencing (VbMS) system that can be used for functional analysis of plant miRNAs. VbMS is performed through tobacco rattle virus-based expression of miRNA target mimics to silence endogenous miRNAs. VbMS of either miR172 or miR165/166 caused developmental defects in Nicotiana benthamiana. VbMS of miR319 reduced the complexity of tomato (Solanum lycopersicum) compound leaves. These results demonstrate that tobacco rattle virus-based VbMS is a powerful tool to silence endogenous miRNAs and to dissect their functions in different plant species. PMID:24296072

Genetic dissection of barley morphology and development.

PubMed

Druka, Arnis; Franckowiak, Jerome; Lundqvist, Udda; Bonar, Nicola; Alexander, Jill; Houston, Kelly; Radovic, Slobodanka; Shahinnia, Fahimeh; Vendramin, Vera; Morgante, Michele; Stein, Nils; Waugh, Robbie

2011-02-01

Since the early 20th century, barley (Hordeum vulgare) has been a model for investigating the effects of physical and chemical mutagens and for exploring the potential of mutation breeding in crop improvement. As a consequence, extensive and well-characterized collections of morphological and developmental mutants have been assembled that represent a valuable resource for exploring a wide range of complex and fundamental biological processes. We constructed a collection of 881 backcrossed lines containing mutant alleles that induce a majority of the morphological and developmental variation described in this species. After genotyping these lines with up to 3,072 single nucleotide polymorphisms, comparison to their recurrent parent defined the genetic location of 426 mutant alleles to chromosomal segments, each representing on average <3% of the barley genetic map. We show how the gene content in these segments can be predicted through conservation of synteny with model cereal genomes, providing a route to rapid gene identification.

LDAP: a web server for lncRNA-disease association prediction.

PubMed

Lan, Wei; Li, Min; Zhao, Kaijie; Liu, Jin; Wu, Fang-Xiang; Pan, Yi; Wang, Jianxin

2017-02-01

Increasing evidences have demonstrated that long noncoding RNAs (lncRNAs) play important roles in many human diseases. Therefore, predicting novel lncRNA-disease associations would contribute to dissect the complex mechanisms of disease pathogenesis. Some computational methods have been developed to infer lncRNA-disease associations. However, most of these methods infer lncRNA-disease associations only based on single data resource. In this paper, we propose a new computational method to predict lncRNA-disease associations by integrating multiple biological data resources. Then, we implement this method as a web server for lncRNA-disease association prediction (LDAP). The input of the LDAP server is the lncRNA sequence. The LDAP predicts potential lncRNA-disease associations by using a bagging SVM classifier based on lncRNA similarity and disease similarity. The web server is available at http://bioinformatics.csu.edu.cn/ldap jxwang@mail.csu.edu.cn. Supplementary data are available at Bioinformatics online.

Exploiting the Lichen Liaison.

ERIC Educational Resources Information Center

Raham, R. Gary

1978-01-01

For teachers in search of an easily obtainable, readily dissectable, and unique living specimen to arouse the interest of their students and illustrate important biological principles, lichens are the perfect selection. Background information and experiments on lichen anatomy, physiology, and chemistry are given. An appendix gives culture media.…

Using Digital Microscopy

ERIC Educational Resources Information Center

Travaille, Madelaine; Adams, Sandra D.

2006-01-01

Studying "Caenorhabditis elegans" ("C. elegans") live cultures provides excellent opportunities for authentic inquiry in a high school anatomy and physiology or other biology lab course. Using a digital dissection microscope, a student can photograph the organism during various stages of development and study and analyze the images. In this…

Biology of Schwann cells.

PubMed

Kidd, Grahame J; Ohno, Nobuhiko; Trapp, Bruce D

2013-01-01

The fundamental roles of Schwann cells during peripheral nerve formation and regeneration have been recognized for more than 100 years, but the cellular and molecular mechanisms that integrate Schwann cell and axonal functions continue to be elucidated. Derived from the embryonic neural crest, Schwann cells differentiate into myelinating cells or bundle multiple unmyelinated axons into Remak fibers. Axons dictate which differentiation path Schwann cells follow, and recent studies have established that axonal neuregulin1 signaling via ErbB2/B3 receptors on Schwann cells is essential for Schwann cell myelination. Extracellular matrix production and interactions mediated by specific integrin and dystroglycan complexes are also critical requisites for Schwann cell-axon interactions. Myelination entails expansion and specialization of the Schwann cell plasma membrane over millimeter distances. Many of the myelin-specific proteins have been identified, and transgenic manipulation of myelin genes have provided novel insights into myelin protein function, including maintenance of axonal integrity and survival. Cellular events that facilitate myelination, including microtubule-based protein and mRNA targeting, and actin based locomotion, have also begun to be understood. Arguably, the most remarkable facet of Schwann cell biology, however, is their vigorous response to axonal damage. Degradation of myelin, dedifferentiation, division, production of axonotrophic factors, and remyelination all underpin the substantial regenerative capacity of the Schwann cells and peripheral nerves. Many of these properties are not shared by CNS fibers, which are myelinated by oligodendrocytes. Dissecting the molecular mechanisms responsible for the complex biology of Schwann cells continues to have practical benefits in identifying novel therapeutic targets not only for Schwann cell-specific diseases but other disorders in which axons degenerate. Copyright © 2013 Elsevier B.V. All rights reserved.

Isolating Spermathecae and Determining Mating Status of Drosophila suzukii: A Protocol for Tissue Dissection and Its Applications

PubMed Central

Avanesyan, Alina; Jaffe, Benjamin D.; Guédot, Christelle

2017-01-01

The spotted wing drosophila, Drosophila suzukii (Diptera: Drosophilidae), is an emerging invasive pest, which attacks a wide variety of fruits and berries. Although previous studies have focused on different aspects of D. suzukii reproductive biology, there are no protocols available for determining the mating status of D. suzukii females and drosophilids in general. In this study, a step-by-step protocol for tissue dissection, isolating spermathecae, and determining the mating status of females was developed specifically for D. suzukii. This protocol is an effective and relatively quick method for determining female mating status. It has important applications from exploring reproductive output of D. suzukii females to understanding the biology of D. suzukii winter morph, which presumably plays the main role in the overwintering of this invasive species. We demonstrated applicability of this protocol for both field collected flies and flies reared in the lab, including fly specimens stored on a long-term basis. PMID:28287438

Anatomical characteristics of the styloid process in internal carotid artery dissection: Case-control study.

PubMed

Amorim, José M; Pereira, Daniela; Rodrigues, Marta G; Beato-Coelho, José; Lopes, Margarida; Cunha, André; Figueiredo, Sofia; Mendes-Pinto, Mafalda; Ferreira, Carla; Sargento-Freitas, João; Castro, Sérgio; Pinho, João

2018-06-01

Introduction Pathophysiology of cervical artery dissection is complex and poorly understood. In addition to well-known causative and predisposing factors, including major trauma and monogenic connective tissue disorders, morphological characteristics of the styloid process have been recently recognized as a possible risk factor for cervical internal carotid artery dissection. Aims To study the association of the anatomical characteristics of styloid process with internal carotid artery dissection. Methods Retrospective, multicenter, case-control study of patients with internal carotid artery dissection and age- and sex-matched controls. Consecutive patients with internal carotid artery dissection and controls with ischemic stroke or transient ischemic attack of any etiology excluding internal carotid artery dissection, who had performed computed tomography angiography, diagnosed between January 2010 and September 2016. Two independent observers measured styloid process length and styloid process distance to internal carotid artery. Results Sixty-two patients with internal carotid artery dissection and 70 controls were included. Interobserver agreement was good for styloid process length and styloid process-internal carotid artery distance (interclass correlation coefficient = 0.89 and 0.76, respectively). Styloid process ipsilateral to dissection was longer than left and right styloid process in controls (35.8 ± 14.4 mm versus 30.4 ± 8.9 mm and 30.3 ± 8.2 mm, p = 0.011 and p = 0.008, respectively). Styloid process-internal carotid artery distance ipsilateral to dissection was shorter than left and right distance in controls (6.3 ± 1.9 mm versus 7.2 ± 2.1 mm and 7.0 ± 2.3 mm, p = 0.003 and p = 0.026, respectively). Internal carotid artery dissection was associated with styloid process length (odds ratio = 1.04 mm -1 , 95% confidence interval = 1.01-1.08, p = 0.015) and styloid process-internal carotid artery distance (OR = 0.77 mm -1 , 95% confidence interval = 0.64-0.92, p = 0.004). Conclusion Longer styloid process and shorter distance between styloid process and cervical internal carotid artery are associated with cervical internal carotid artery dissection.

Complex Genetics of Behavior: BXDs in the Automated Home-Cage.

PubMed

Loos, Maarten; Verhage, Matthijs; Spijker, Sabine; Smit, August B

2017-01-01

This chapter describes a use case for the genetic dissection and automated analysis of complex behavioral traits using the genetically diverse panel of BXD mouse recombinant inbred strains. Strains of the BXD resource differ widely in terms of gene and protein expression in the brain, as well as in their behavioral repertoire. A large mouse resource opens the possibility for gene finding studies underlying distinct behavioral phenotypes, however, such a resource poses a challenge in behavioral phenotyping. To address the specifics of large-scale screening we describe how to investigate: (1) how to assess mouse behavior systematically in addressing a large genetic cohort, (2) how to dissect automation-derived longitudinal mouse behavior into quantitative parameters, and (3) how to map these quantitative traits to the genome, deriving loci underlying aspects of behavior.

Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut.

PubMed

Hemsworth, Glyn R; Thompson, Andrew J; Stepper, Judith; Sobala, Łukasz F; Coyle, Travis; Larsbrink, Johan; Spadiut, Oliver; Goddard-Borger, Ethan D; Stubbs, Keith A; Brumer, Harry; Davies, Gideon J

2016-07-01

The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta)genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-l-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins. © 2016 The Authors.

A Powerful Approach to Estimating Annotation-Stratified Genetic Covariance via GWAS Summary Statistics.

PubMed

Lu, Qiongshi; Li, Boyang; Ou, Derek; Erlendsdottir, Margret; Powles, Ryan L; Jiang, Tony; Hu, Yiming; Chang, David; Jin, Chentian; Dai, Wei; He, Qidu; Liu, Zefeng; Mukherjee, Shubhabrata; Crane, Paul K; Zhao, Hongyu

2017-12-07

Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses, we demonstrate that our method provides accurate covariance estimates, thereby enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (N total ≈ 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimer disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOAD's correlation with cognitive traits and hints at an autoimmune component for ALS. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

NetDecoder: a network biology platform that decodes context-specific biological networks and gene activities.

PubMed

da Rocha, Edroaldo Lummertz; Ung, Choong Yong; McGehee, Cordelia D; Correia, Cristina; Li, Hu

2016-06-02

The sequential chain of interactions altering the binary state of a biomolecule represents the 'information flow' within a cellular network that determines phenotypic properties. Given the lack of computational tools to dissect context-dependent networks and gene activities, we developed NetDecoder, a network biology platform that models context-dependent information flows using pairwise phenotypic comparative analyses of protein-protein interactions. Using breast cancer, dyslipidemia and Alzheimer's disease as case studies, we demonstrate NetDecoder dissects subnetworks to identify key players significantly impacting cell behaviour specific to a given disease context. We further show genes residing in disease-specific subnetworks are enriched in disease-related signalling pathways and information flow profiles, which drive the resulting disease phenotypes. We also devise a novel scoring scheme to quantify key genes-network routers, which influence many genes, key targets, which are influenced by many genes, and high impact genes, which experience a significant change in regulation. We show the robustness of our results against parameter changes. Our network biology platform includes freely available source code (http://www.NetDecoder.org) for researchers to explore genome-wide context-dependent information flow profiles and key genes, given a set of genes of particular interest and transcriptome data. More importantly, NetDecoder will enable researchers to uncover context-dependent drug targets. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Along the Central Dogma-Controlling Gene Expression with Small Molecules.

PubMed

Schneider-Poetsch, Tilman; Yoshida, Minoru

2018-05-04

The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Environmental and hormonal control of cambial stem cell dynamics.

PubMed

Bhalerao, Rishikesh P; Fischer, Urs

2017-01-01

Perennial trees have the amazing ability to adjust their growth rate to both adverse and favorable seasonally reoccurring environmental conditions over hundreds of years. In trunks and stems, the basis for the tuning of seasonal growth rate is the regulation of cambial stem cell activity. Cambial stem cell quiescence and dormancy protect the tree from potential physiological and genomic damage caused by adverse growing conditions and may permit a long lifespan. Cambial dormancy and longevity are both aspects of a tree's life for which the study of cambial stem cell behavior in the annual model plant Arabidopsis is inadequate. Recent functional analyses of hormone perception and catabolism mutants in Populus indicate that shoot-derived long-range signals, as well as local cues, steer cambial activity. Auxin is central to the regulation of cambial activity and probably also maintenance. Emerging genome editing and phenotyping technologies will enable the identification of down-stream targets of hormonal action and facilitate the genetic dissection of complex traits of cambial biology. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Investigation of pulsatile flowfield in healthy thoracic aorta models.

PubMed

Wen, Chih-Yung; Yang, An-Shik; Tseng, Li-Yu; Chai, Jyh-Wen

2010-02-01

Cardiovascular disease is the primary cause of morbidity and mortality in the western world. Complex hemodynamics plays a critical role in the development of aortic dissection and atherosclerosis, as well as many other diseases. Since fundamental fluid mechanics are important for the understanding of the blood flow in the cardiovascular circulatory system of the human body aspects, a joint experimental and numerical study was conducted in this study to determine the distributions of wall shear stress and pressure and oscillatory WSS index, and to examine their correlation with the aortic disorders, especially dissection. Experimentally, the Phase-Contrast Magnetic Resonance Imaging (PC-MRI) method was used to acquire the true geometry of a normal human thoracic aorta, which was readily converted into a transparent thoracic aorta model by the rapid prototyping (RP) technique. The thoracic aorta model was then used in the in vitro experiments and computations. Simulations were performed using the computational fluid dynamic (CFD) code ACE+((R)) to determine flow characteristics of the three-dimensional, pulsatile, incompressible, and Newtonian fluid in the thoracic aorta model. The unsteady boundary conditions at the inlet and the outlet of the aortic flow were specified from the measured flowrate and pressure results during in vitro experiments. For the code validation, the predicted axial velocity reasonably agrees with the PC-MRI experimental data in the oblique sagittal plane of the thoracic aorta model. The thorough analyses of the thoracic aorta flow, WSSs, WSS index (OSI), and wall pressures are presented. The predicted locations of the maxima of WSS and the wall pressure can be then correlated with that of the thoracic aorta dissection, and thereby may lead to a useful biological significance. The numerical results also suggest that the effects of low WSS and high OSI tend to cause wall thickening occurred along the inferior wall of the aortic arch and the anterior wall of the brachiocephalic artery, similar implication reported in a number of previous studies.

How to pattern a leaf

USDA-ARS?s Scientific Manuscript database

Leaf development presents a tremendous resource for tackling the question of patterning in biology. Leaves can be simple or highly dissected. They may have elaborated parts such as the tendrils of a pea leaf or the rolled blade of a carnivorous pitcher plant. Despite the variation in size, shape, an...

The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection

PubMed Central

Latini, Francesco; Hjortberg, Mats; Aldskogius, Håkan; Ryttlefors, Mats

2015-01-01

The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity. PMID:26063964

The effect of distributed virtual reality simulation training on cognitive load during subsequent dissection training.

PubMed

Andersen, Steven Arild Wuyts; Konge, Lars; Sørensen, Mads Sølvsten

2018-05-07

Complex tasks such as surgical procedures can induce excessive cognitive load (CL), which can have a negative effect on learning, especially for novices. To investigate if repeated and distributed virtual reality (VR) simulation practice induces a lower CL and higher performance in subsequent cadaveric dissection training. In a prospective, controlled cohort study, 37 residents in otorhinolaryngology received VR simulation training either as additional distributed practice prior to course participation (intervention) (9 participants) or as standard practice during the course (control) (28 participants). Cognitive load was estimated as the relative change in secondary-task reaction time during VR simulation and cadaveric procedures. Structured distributed VR simulation practice resulted in lower mean reaction times (32% vs. 47% for the intervention and control group, respectively, p < 0.01) as well as a superior final-product performance during subsequent cadaveric dissection training. Repeated and distributed VR simulation causes a lower CL to be induced when the learning situation is increased in complexity. A suggested mechanism is the formation of mental schemas and reduction of the intrinsic CL. This has potential implications for surgical skills training and suggests that structured, distributed training be systematically implemented in surgical training curricula.

A novel approach for the generation of genetically modified mammary epithelial cell cultures yields new insights into TGFβ signaling in the mammary gland

PubMed Central

2010-01-01

Introduction Molecular dissection of the signaling pathways that underlie complex biological responses in the mammary epithelium is limited by the difficulty of propagating large numbers of mouse mammary epithelial cells, and by the inability of ribonucleic acid interference-based knockdown approaches to fully ablate gene function. Here we describe a method for the generation of conditionally immortalized mammary epithelial cells with defined genetic defects, and we show how such cells can be used to investigate complex signal transduction processes using the transforming growth factor beta (TGFβ)/Smad pathway as an example. Methods We intercrossed the previously described H-2Kb-tsA58 transgenic mouse (Immortomouse), which expresses a temperature-sensitive mutant of the simian virus-40 large T-antigen (tsTAg), with mice of differing Smad genotypes. Conditionally immortalized mammary epithelial cell cultures were derived from the virgin mammary glands of offspring of these crosses and were used to assess the Smad dependency of different biological responses to TGFβ. Results IMECs could be propagated indefinitely at permissive temperatures and had a stable epithelial phenotype, resembling primary mammary epithelial cells with respect to several criteria, including responsiveness to TGFβ. Using this panel of cells, we demonstrated that Smad3, but not Smad2, is necessary for TGFβ-induced apoptotic, growth inhibitory and epithelial-to-mesenchymal transition responses, whereas either Smad2 or Smad3 can support TGFβ-induced invasion as long as a threshold level of total Smad is exceeded. Conclusions The present work demonstrates the practicality and utility of generating conditionally immortalized mammary epithelial cell lines from genetically modified Immortomice for detailed investigation of complex signaling pathways in the mammary epithelium. PMID:20942910

Use of Multivariate Linkage Analysis for Dissection of a Complex Cognitive Trait

PubMed Central

Marlow, Angela J.; Fisher, Simon E.; Francks, Clyde; MacPhie, I. Laurence; Cherny, Stacey S.; Richardson, Alex J.; Talcott, Joel B.; Stein, John F.; Monaco, Anthony P.; Cardon, Lon R.

2003-01-01

Replication of linkage results for complex traits has been exceedingly difficult, owing in part to the inability to measure the precise underlying phenotype, small sample sizes, genetic heterogeneity, and statistical methods employed in analysis. Often, in any particular study, multiple correlated traits have been collected, yet these have been analyzed independently or, at most, in bivariate analyses. Theoretical arguments suggest that full multivariate analysis of all available traits should offer more power to detect linkage; however, this has not yet been evaluated on a genomewide scale. Here, we conduct multivariate genomewide analyses of quantitative-trait loci that influence reading- and language-related measures in families affected with developmental dyslexia. The results of these analyses are substantially clearer than those of previous univariate analyses of the same data set, helping to resolve a number of key issues. These outcomes highlight the relevance of multivariate analysis for complex disorders for dissection of linkage results in correlated traits. The approach employed here may aid positional cloning of susceptibility genes in a wide spectrum of complex traits. PMID:12587094

Freeze-Drying as Sample Preparation for Micellar Electrokinetic Capillary Chromatography – Electrochemical Separations of Neurochemicals in Drosophila Brains

PubMed Central

Berglund, E. Carina; Kuklinski, Nicholas J.; Karagündüz, Ekin; Ucar, Kubra; Hanrieder, Jörg; Ewing, Andrew G.

2013-01-01

Micellar electrokinetic capillary chromatography with electrochemical detection has been used to quantify biogenic amines in freeze-dried Drosophila melanogaster brains. Freeze drying samples offers a way to preserve the biological sample while making dissection of these tiny samples easier and faster. Fly samples were extracted in cold acetone and dried in a rotary evaporator. Extraction and drying times were optimized in order to avoid contamination by red-pigment from the fly eyes and still have intact brain structures. Single freeze-dried fly-brain samples were found to produce representative electropherograms as a single hand-dissected brain sample. Utilizing the faster dissection time that freeze drying affords, the number of brains in a fixed homogenate volume can be increased to concentrate the sample. Thus, concentrated brain samples containing five or fifteen preserved brains were analyzed for their neurotransmitter content, and five analytes; dopamine N-acetyloctopamine, Nacetylserotonin, N-acetyltyramine, N-acetyldopamine were found to correspond well with previously reported values. PMID:23387977

Genomics and Genetics in the Biology of Adaptation to Exercise

PubMed Central

Bouchard, Claude; Rankinen, Tuomo; Timmons, James A.

2014-01-01

This chapter is devoted to the role of genetic variation and gene-exercise interactions in the biology of adaptation to exercise. There is evidence from genetic epidemiology research that DNA sequence differences contribute to human variation in physical activity level, cardiorespiratory fitness in the untrained state, cardiovascular and metabolic response to acute exercise, and responsiveness to regular exercise. Methodological and technological advances have made it possible to undertake the molecular dissection of the genetic component of complex, multifactorial traits, such as those of interest to exercise biology, in terms of tissue expression profile, genes, and allelic variants. The evidence from animal models and human studies is considered. Data on candidate genes, genome-wide linkage results, genome-wide association findings, expression arrays, and combinations of these approaches are reviewed. Combining transcriptomic and genomic technologies has been shown to be more powerful as evidenced by the development of a recent molecular predictor of the ability to increase VO2max with exercise training. For exercise as a behavior and physiological fitness as a state to be major players in public health policies will require that that the role of human individuality and the influence of DNA sequence differences be understood. Likewise, progress in the use of exercise in therapeutic medicine will depend to a large extent on our ability to identify the favorable responders for given physiological properties to a given exercise regimen. PMID:23733655

A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. | Office of Cancer Genomics

Cancer.gov

Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis.

Dissecting the HMO-benefits managers relationship: what to measure and why.

PubMed

Peltier, J W; Westfall, J

2000-01-01

The relationship between health maintenance organizations (HMO) and employee benefits managers (EBM) is multidimensional and complex. Relationship marketing theory is used to illustrate its role in strengthening interorganizational bonds and reducing defections to other health plans. The importance of various service dimensions in the HMO-EBM relationship can change depending on whether the measure used is overall satisfaction, overall quality, and loyalty to the HMO. By dissecting relationships in this way, HMOs can develop strategies that take multiple routes for building and maintaining strong partnerships with employee benefits managers.

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

PubMed Central

Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

2015-01-01

Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

Dissecting non-additive genetic effects for production and reproductive traits in dairy cattle

USDA-ARS?s Scientific Manuscript database

Genomic imprinting is an epigenetic mechanism by which a parent-of-origin-specific allele is silenced and only the other allele is expressed. Both dominance and imprinting play an important role in mammalian biology and development. Though one may naturally assume that dominance and imprinting effec...

Anatomy for Biomedical Engineers

ERIC Educational Resources Information Center

Carmichael, Stephen W.; Robb, Richard A.

2008-01-01

There is a perceived need for anatomy instruction for graduate students enrolled in a biomedical engineering program. This appeared especially important for students interested in and using medical images. These students typically did not have a strong background in biology. The authors arranged for students to dissect regions of the body that…

Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle

USDA-ARS?s Scientific Manuscript database

Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and wheth...

Evolutionary Biology Digital Dissection Project: Web-Based Laboratory Learning Opportunities for Students

ERIC Educational Resources Information Center

Fabian, Carole Ann

2004-01-01

A university in Buffalo introduced its students to evolution by providing them with information on evidence of evolution, mechanisms for evolution, principles of genetics, selection, adaptation, evolution and sociobiology. This method of teaching with technology enabled students to improve and expand their learning opportunities.

Time-saving and fail-safe dissection method for vestibulocochlear organs in gross anatomy classes.

PubMed

Suzuki, Ryoji; Konno, Naoaki; Ishizawa, Akimitsu; Kanatsu, Yoshinori; Funakoshi, Kodai; Akashi, Hideo; Zhou, Ming; Abe, Hiroshi

2017-09-01

Because the vestibulocochlear organs are tiny and complex, and are covered by the petrous part of the temporal bone, they are very difficult for medical students to dissect and visualize during gross anatomy classes. Here, we report a time-saving and fail-safe procedure we have devised, using a hand-held hobby router. Nine en bloc temporal bone samples from donated human cadavers were used as trial materials for devising an appropriate procedure for dissecting the vestibulocochlear organs. A hand-held hobby router was used to cut through the temporal bone. After trials, the most time-saving and fail-safe method was selected. The performance of the selected method was assessed by a survey of 242 sides of 121 cadavers during gross anatomy classes for vestibulocochlear dissection. The assessment was based on the observation ratio. The best procedure appeared to be removal of the external acoustic meatus roof and tympanic cavity roof together with removal of the internal acoustic meatus roof. The whole procedure was completed within two dissection classes, each lasting 4.5 hr. The ratio of surveillance for the chorda tympani and three semicircular canals by students was significantly improved during 2013 through 2016. In our dissection class, "removal of the external acoustic meatus roof and tympanic cavity roof together with removal of the internal acoustic meatus roof" was the best procedure for students in the limited time available. Clin. Anat. 30:703-710, 2017. © 2017Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Acute aortic syndromes: new insights from electrocardiographically gated computed tomography.

PubMed

Fleischmann, Dominik; Mitchell, R Scott; Miller, D Craig

2008-01-01

The development of retrospective electrocardiographic (ECG)-gating has proved to be a diagnostic and therapeutic boon for computed tomography (CT) imaging of patients with acute thoracic aortic diseases, such as aortic dissection/intramural hematoma (AD/IMH), penetrating atherosclerotic ulcer (APU), and ruptured/leaking aneurysm. The notorious pulsation motion artifacts in the ascending aorta confounding regular CT scanning can be eliminated, and involvement of the sinuses of Valsalva, the valve cusps, the aortic annulus, and the coronary arteries in aortic dissection can be clearly depicted or excluded. Motion-free images also allow reliable identification of the site of the primary intimal tear, the location, and extent of the intimomedial flap, and branch artery involvement. ECG-gated CTA also allows the detection of more subtle lesions and variants of aortic dissection, which may ultimately expand our understanding of these complex, life-threatening disorders.

Demonstration of pelvic anatomy by modified midline transection that maintains intact internal pelvic organs.

PubMed

Steinke, Hanno; Saito, Toshiyuki; Herrmann, Gudrun; Miyaki, Takayoshi; Hammer, Niels; Sandrock, Mara; Itoh, Masahiro; Spanel-Borowski, Katharina

2010-01-01

Gross dissection for demonstrating anatomy of the human pelvis has traditionally involved one of two approaches, each with advantages and disadvantages. Classic hemisection in the median plane through the pelvic ring transects the visceral organs but maintains two symmetric pelvic halves. An alternative paramedial transection compromises one side of the bony pelvis but leaves the internal organs intact. The authors propose a modified technique that combines advantages of both classical dissections. This novel approach involves dividing the pubic symphysis and sacrum in the median plane after shifting all internal organs to one side. The hemipelvis without internal organs is immediately available for further dissection of the lower limb. The hemipelvis with intact internal organs is ideal for showing the complex spatial relationships of the pelvic organs and vessels relative to the intact pelvic floor.

A guide for effective anatomical vascularization studies: useful ex vivo methods for both CT and MRI imaging before dissection.

PubMed

Renard, Yohann; Hossu, Gabriela; Chen, Bailiang; Krebs, Marine; Labrousse, Marc; Perez, Manuela

2018-01-01

The objective of this study was to develop a simple and useful injection protocol for imaging cadaveric vascularization and dissection. Mixtures of contrast agent and cast product should provide adequate contrast for two types of ex vivo imaging (MRI and CT) and should harden to allow gross dissection of the injected structures. We tested the most popular contrast agents and cast products, and selected the optimal mixture composition based on their availability and ease of use. All mixtures were first tested in vitro to adjust dilution parameters of each contrast agent and to fine-tune MR imaging acquisition sequences. Mixtures were then injected in 24 pig livers and one human pancreas for MR and computed tomography (CT) imaging before anatomical dissection. Colorized latex, gadobutrol and barite mixture met the above objective. Mixtures composed of copper sulfate (CuSO 4 ) gadoxetic acid (for MRI) and iodine (for CT) gave an inhomogeneous signal or extravasation of the contrast agent. Agar did not harden sufficiently for gross dissection but appears useful for CT and magnetic resonance imaging (MRI) studies without dissection. Silicone was very hard to inject but achieved the goals of the study. Resin is particularly difficult to use but could replace latex as an alternative for corrosion instead of dissection. This injection protocol allows CT and MRI images to be obtained of cadaveric vascularization and anatomical casts in the same anatomic specimen. Post-imaging processing software allow easy 3D reconstruction of complex anatomical structures using this technique. Applications are numerous, e.g. surgical training, teaching methods, postmortem anatomic studies, pathologic studies, and forensic diagnoses. © 2017 Anatomical Society.

On the necessity of dissecting sequence similarity scores into segment-specific contributions for inferring protein homology, function prediction and annotation

PubMed Central

2014-01-01

Background Protein sequence similarities to any types of non-globular segments (coiled coils, low complexity regions, transmembrane regions, long loops, etc. where either positional sequence conservation is the result of a very simple, physically induced pattern or rather integral sequence properties are critical) are pertinent sources for mistaken homologies. Regretfully, these considerations regularly escape attention in large-scale annotation studies since, often, there is no substitute to manual handling of these cases. Quantitative criteria are required to suppress events of function annotation transfer as a result of false homology assignments. Results The sequence homology concept is based on the similarity comparison between the structural elements, the basic building blocks for conferring the overall fold of a protein. We propose to dissect the total similarity score into fold-critical and other, remaining contributions and suggest that, for a valid homology statement, the fold-relevant score contribution should at least be significant on its own. As part of the article, we provide the DissectHMMER software program for dissecting HMMER2/3 scores into segment-specific contributions. We show that DissectHMMER reproduces HMMER2/3 scores with sufficient accuracy and that it is useful in automated decisions about homology for instructive sequence examples. To generalize the dissection concept for cases without 3D structural information, we find that a dissection based on alignment quality is an appropriate surrogate. The approach was applied to a large-scale study of SMART and PFAM domains in the space of seed sequences and in the space of UniProt/SwissProt. Conclusions Sequence similarity core dissection with regard to fold-critical and other contributions systematically suppresses false hits and, additionally, recovers previously obscured homology relationships such as the one between aquaporins and formate/nitrite transporters that, so far, was only supported by structure comparison. PMID:24890864

Three-Dimensional Anatomy of the White Matter Fibers of the Temporal Lobe: Surgical Implications.

PubMed

Pescatori, Lorenzo; Tropeano, Maria Pia; Manfreda, Andrea; Delfini, Roberto; Santoro, Antonio

2017-04-01

The aim of this work is to describe in detail the complex 3-dimensional organization of the white matter of the temporal lobe and discuss the surgical implications of the approaches to lesions located into the mesial temporal region and within the temporal horn and the atrium of the lateral ventricles. Sixteen human cerebral hemispheres fixed in a 10% formalin solution for at least 40 days were studied. After removal of the arachnoid membrane, the hemispheres were frozen at -15°C for at least 14 days, and the Klingler technique, which consists of the microscopic dissection and progressive identification of white matter fibers, was performed. The dissection allowed us to appreciate the topographical organization of the white matter of the temporal lobe identifying the most important association, projection, and commissural fasciculi. The dissection from the lateral side allowed the progressive visualization of the superior longitudinal fasciculus and its components, the extreme and external capsule, the uncinate fasciculus, the inferior fronto-occipital fasciculus, the anterior commissure, the internal capsule, and the optic radiations. The dissection was completed from the inferior and medial side for identification of the cingulum and the fornix. The complex 3-dimensional organization of the white matter substance of the temporal lobe is characterized by 2 main systems of boundaries: the sagittal stratum and the temporal stem. Their knowledge is essential for the appropriate treatment of pathologies localized in this region as demonstrated by the 2 clinical cases presented in this work. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of candidate genes with drought tolerance traits in diverse perennial ryegrass accessions

Treesearch

Xiaoqing Yu; Guihua Bai; Shuwei Liu; Na Luo; Ying Wang; Douglas S. Richmond; Paula M. Pijut; Scott A. Jackson; Jianming Yu; Yiwei Jiang

2013-01-01

Drought is a major environmental stress limiting growth of perennial grasses in temperate regions. Plant drought tolerance is a complex trait that is controlled by multiple genes. Candidate gene association mapping provides a powerful tool for dissection of complex traits. Candidate gene association mapping of drought tolerance traits was conducted in 192 diverse...

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.

PubMed

Willms, Eduard; Cabañas, Carlos; Mäger, Imre; Wood, Matthew J A; Vader, Pieter

2018-01-01

Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.

Acorns Alive.

ERIC Educational Resources Information Center

Matthews, Catherine; Vickers, Valerie; Patrick, Patricia

2002-01-01

Introduces a lesson plan on the role of the acorn and its complex community of biotic relationships between animal and fungal organisms. Introduces students to ecological concepts through acorn investigations including dissection of acorns and exploring the organisms' interaction web. (YDS)

Chromatin regulation at the frontier of synthetic biology.

PubMed

Keung, Albert J; Joung, J Keith; Khalil, Ahmad S; Collins, James J

2015-03-01

As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including 'epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication.

Chromatin regulation at the frontier of synthetic biology

PubMed Central

Keung, Albert J.; Joung, J. Keith; Khalil, Ahmad S.; Collins, James J.

2016-01-01

As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including `epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. PMID:25668787

Student-Centered Deliberations of Ethical Care & Use of Animals

ERIC Educational Resources Information Center

Pecore, John; Demetrikopoulos, Melissa; Frantz, Kyle

2007-01-01

Most biology teachers implement animal dissection (real or virtual) and often lead discussions on research involving animal subjects. Such activities provide excellent opportunities to explore ideas about ethical conduct in the care and use of animals. The challenge for teachers is to present information about animal care and use that enables…

Morphology of the female reproductive system and physiological age-grading of Megamelus scutellaris (Hemiptera: Delphacidae), a biological control agent of water hyacinth

USDA-ARS?s Scientific Manuscript database

The morphology of the female reproductive system in Megamelus scutellaris Berg (Hemiptera:Delphacidae), a biocontrol agent of Eichhornia crassipes (Mart.) Solms, was examined using standard light microscopy techniques. Ovaries extracted from individuals dissected in phosphate buffered saline were ex...

Bodily Experiences in Secondary School Biology

ERIC Educational Resources Information Center

Orlander, Auli Arvola; Wickman, Per-Olof

2011-01-01

This is a study of teaching about the human body. It is based on transcribed material from interviews with 15-year-old students and teachers about their experiences of sex education and from recordings of classroom interactions during a dissection. The analysis is focused on the relationship between what students are supposed to learn about the…

"No interest in human anatomy as such": Frederic Wood Jones dissects anatomical investigation in the United States in the 1920s.

PubMed

Jones, Ross L

2014-03-01

In 1926, Frederic Wood Jones, professor of Anatomy at the University of Adelaide and a leading figure in the British anatomical world, took a Rockefeller Foundation funded trip to the United States in order to inspect anatomy programmes and medical museums and to meet leading figures in the anatomical and anthropological world. His later reflections paint a picture of a discipline in transition. Physical anthropology and gross anatomy were coming to a crisis point in the United States, increasingly displaced by research in histology, embryology and radiological anatomy. Meanwhile, in Britain and its colonial outposts, anatomists such as Wood Jones were attempting to re-invigorate the discipline in the field, studying biological specimens as functional and active agents in their particular milieus, but with human dissection at the core. Thus, an examination of this trip allows us to see how the interaction between two traditions in anatomy informed the process of the development of human biology in this critical period. Copyright © 2013 Elsevier Ltd. All rights reserved.

Covering Science as a Mass Media Fellow

NASA Astrophysics Data System (ADS)

McMeeking, Gavin R.

2006-03-01

I remember my first unpleasant biology lab dissection in high school. I am not sure if the experience was worse for me or for the unfortunate fetal pig we dissected that day. The sights and smells of that fateful morning forever put me on a path toward the physical sciences, and probably have a lot to do with my ending up as a graduate student in atmospheric chemistry instead of at some medical school cutting up dead bodies. So imagine my horror after encountering the leg of a dead horse as I walked into a bioengineering laboratory to report on a story about artificial joint research. Subjecting myself to such biological horrors, though, was part of my duties as an AGU-sponsored American Association for the Advancement of Science Mass Media Fellow. The program places graduate students and recent graduates from scientific fields in major media outlets throughout the country. The aim of the program is to give science-trained individuals a taste of a career in science journalism as well as to help scientists develop better communication skills.

Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum

PubMed Central

2012-01-01

Background The post-genomic era of malaria research provided unprecedented insights into the biology of Plasmodium parasites. Due to the large evolutionary distance to model eukaryotes, however, we lack a profound understanding of many processes in Plasmodium biology. One example is the cell nucleus, which controls the parasite genome in a development- and cell cycle-specific manner through mostly unknown mechanisms. To study this important organelle in detail, we conducted an integrative analysis of the P. falciparum nuclear proteome. Results We combined high accuracy mass spectrometry and bioinformatic approaches to present for the first time an experimentally determined core nuclear proteome for P. falciparum. Besides a large number of factors implicated in known nuclear processes, one-third of all detected proteins carry no functional annotation, including many phylum- or genus-specific factors. Importantly, extensive experimental validation using 30 transgenic cell lines confirmed the high specificity of this inventory, and revealed distinct nuclear localization patterns of hitherto uncharacterized proteins. Further, our detailed analysis identified novel protein domains potentially implicated in gene transcription pathways, and sheds important new light on nuclear compartments and processes including regulatory complexes, the nucleolus, nuclear pores, and nuclear import pathways. Conclusion Our study provides comprehensive new insight into the biology of the Plasmodium nucleus and will serve as an important platform for dissecting general and parasite-specific nuclear processes in malaria parasites. Moreover, as the first nuclear proteome characterized in any protist organism, it will provide an important resource for studying evolutionary aspects of nuclear biology. PMID:23181666

Rapid response to changing environments during biological invasions: DNA methylation perspectives.

PubMed

Huang, Xuena; Li, Shiguo; Ni, Ping; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin

2017-12-01

Dissecting complex interactions between species and their environments has long been a research hot spot in the fields of ecology and evolutionary biology. The well-recognized Darwinian evolution has well-explained long-term adaptation scenarios; however, "rapid" processes of biological responses to environmental changes remain largely unexplored, particularly molecular mechanisms such as DNA methylation that have recently been proposed to play crucial roles in rapid environmental adaptation. Invasive species, which have capacities to successfully survive rapidly changing environments during biological invasions, provide great opportunities to study molecular mechanisms of rapid environmental adaptation. Here, we used the methylation-sensitive amplified polymorphism (MSAP) technique in an invasive model ascidian, Ciona savignyi, to investigate how species interact with rapidly changing environments at the whole-genome level. We detected quite rapid DNA methylation response: significant changes of DNA methylation frequency and epigenetic differentiation between treatment and control groups occurred only after 1 hr of high-temperature exposure or after 3 hr of low-salinity challenge. In addition, we detected time-dependent hemimethylation changes and increased intragroup epigenetic divergence induced by environmental stresses. Interestingly, we found evidence of DNA methylation resilience, as most stress-induced DNA methylation variation maintained shortly (~48 hr) and quickly returned back to the control levels. Our findings clearly showed that invasive species could rapidly respond to acute environmental changes through DNA methylation modifications, and rapid environmental changes left significant epigenetic signatures at the whole-genome level. All these results provide fundamental background to deeply investigate the contribution of DNA methylation mechanisms to rapid contemporary environmental adaptation. © 2017 John Wiley & Sons Ltd.

Advances in Procedural Techniques - Antegrade

PubMed Central

Wilson, William; Spratt, James C.

2014-01-01

There have been many technological advances in antegrade CTO PCI, but perhaps most importantly has been the evolution of the “hybrid’ approach where ideally there exists a seamless interplay of antegrade wiring, antegrade dissection re-entry and retrograde approaches as dictated by procedural factors. Antegrade wire escalation with intimal tracking remains the preferred initial strategy in short CTOs without proximal cap ambiguity. More complex CTOs, however, usually require either a retrograde or an antegrade dissection re-entry approach, or both. Antegrade dissection re-entry is well suited to long occlusions where there is a healthy distal vessel and limited “interventional” collaterals. Early use of a dissection re-entry strategy will increase success rates, reduce complications, and minimise radiation exposure, contrast use as well as procedural times. Antegrade dissection can be achieved with a knuckle wire technique or the CrossBoss catheter whilst re-entry will be achieved in the most reproducible and reliable fashion by the Stingray balloon/wire. It should be avoided where there is potential for loss of large side branches. It remains to be seen whether use of newer dissection re-entry strategies will be associated with lower restenosis rates compared with the more uncontrolled subintimal tracking strategies such as STAR and whether stent insertion in the subintimal space is associated with higher rates of late stent malapposition and stent thrombosis. It is to be hoped that the algorithms, which have been developed to guide CTO operators, allow for a better transfer of knowledge and skills to increase uptake and acceptance of CTO PCI as a whole. PMID:24694104

Anatomy of the Limbic White Matter Tracts as Revealed by Fiber Dissection and Tractography.

PubMed

Pascalau, Raluca; Popa Stănilă, Roxana; Sfrângeu, Silviu; Szabo, Bianca

2018-05-01

The limbic tracts are involved in crucial cerebral functions such as memory, emotion, and behavior. The complex architecture of the limbic circuit makes it harder to approach compared with other white matter networks. Our study aims to describe the 3-dimensional anatomy of the limbic white matter by the use of 2 complementary study methods, namely ex vivo fiber dissection and in vivo magnetic resonance imaging-based tractography. Three fiber dissection protocols were performed using blunt wooden instruments and a surgical microscope on formalin-fixed brains prepared according to the Klingler method. Diffusion tensor imaging acquisitions were done with a 3-Tesla magnetic resonance scanner on patients with head and neck pathology that did not involve the brain. Fiber tracking was performed with manually selected regions of interest. Cingulum, fornix, the anterior thalamic peduncle, the accumbofrontal bundle, medial forebrain bundle, the uncinate fasciculus, the mammillothalamic tract, ansa peduncularis, and stria terminalis were dissected and fiber tracked. For each tract, location, configuration, segmentation, dimensions, dissection and tractography particularities, anatomical relations, and terminations are described. The limbic white matter tracts were systematized as 2 concentric rings around the thalamus. The inner ring is formed by fornix, mammillothalamic tract, ansa peduncularis, stria terminalis, accumbofrontal fasciculus, and medial forebrain bundle and anterior thalamic peduncle, and the outer ring is formed by the cingulum and uncinate fasciculus. This paper proposes a fiber-tracking protocol for the limbic tracts inspired and validated by fiber dissection findings that can be used routinely in the clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessing the complex architecture of polygenic traits in diverged yeast populations.

PubMed

Cubillos, Francisco A; Billi, Eleonora; Zörgö, Enikö; Parts, Leopold; Fargier, Patrick; Omholt, Stig; Blomberg, Anders; Warringer, Jonas; Louis, Edward J; Liti, Gianni

2011-04-01

Phenotypic variation arising from populations adapting to different niches has a complex underlying genetic architecture. A major challenge in modern biology is to identify the causative variants driving phenotypic variation. Recently, the baker's yeast, Saccharomyces cerevisiae has emerged as a powerful model for dissecting complex traits. However, past studies using a laboratory strain were unable to reveal the complete architecture of polygenic traits. Here, we present a linkage study using 576 recombinant strains obtained from crosses of isolates representative of the major lineages. The meiotic recombinational landscape appears largely conserved between populations; however, strain-specific hotspots were also detected. Quantitative measurements of growth in 23 distinct ecologically relevant environments show that our recombinant population recapitulates most of the standing phenotypic variation described in the species. Linkage analysis detected an average of 6.3 distinct QTLs for each condition tested in all crosses, explaining on average 39% of the phenotypic variation. The QTLs detected are not constrained to a small number of loci, and the majority are specific to a single cross-combination and to a specific environment. Moreover, crosses between strains of similar phenotypes generate greater variation in the offspring, suggesting the presence of many antagonistic alleles and epistatic interactions. We found that subtelomeric regions play a key role in defining individual quantitative variation, emphasizing the importance of the adaptive nature of these regions in natural populations. This set of recombinant strains is a powerful tool for investigating the complex architecture of polygenic traits. © 2011 Blackwell Publishing Ltd.

ICGC PedBrain: Dissecting the genomic complexity underlying medulloblastoma

PubMed Central

Jones, David TW; Jäger, Natalie; Kool, Marcel; Zichner, Thomas; Hutter, Barbara; Sultan, Marc; Cho, Yoon-Jae; Pugh, Trevor J; Hovestadt, Volker; Stütz, Adrian M; Rausch, Tobias; Warnatz, Hans-Jörg; Ryzhova, Marina; Bender, Sebastian; Sturm, Dominik; Pleier, Sabrina; Cin, Huriye; Pfaff, Elke; Sieber, Laura; Wittmann, Andrea; Remke, Marc; Witt, Hendrik; Hutter, Sonja; Tzaridis, Theophilos; Weischenfeldt, Joachim; Raeder, Benjamin; Avci, Meryem; Amstislavskiy, Vyacheslav; Zapatka, Marc; Weber, Ursula D; Wang, Qi; Lasitschka, Bärbel; Bartholomae, Cynthia C; Schmidt, Manfred; von Kalle, Christof; Ast, Volker; Lawerenz, Chris; Eils, Jürgen; Kabbe, Rolf; Benes, Vladimir; van Sluis, Peter; Koster, Jan; Volckmann, Richard; Shih, David; Betts, Matthew J; Russell, Robert B; Coco, Simona; Tonini, Gian Paolo; Schüller, Ulrich; Hans, Volkmar; Graf, Norbert; Kim, Yoo-Jin; Monoranu, Camelia; Roggendorf, Wolfgang; Unterberg, Andreas; Herold-Mende, Christel; Milde, Till; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Maass, Eberhard; Rössler, Jochen; Ebinger, Martin; Schuhmann, Martin U; Frühwald, Michael C; Hasselblatt, Martin; Jabado, Nada; Rutkowski, Stefan; von Bueren, André O; Williamson, Dan; Clifford, Steven C; McCabe, Martin G; Collins, V. Peter; Wolf, Stephan; Wiemann, Stefan; Lehrach, Hans; Brors, Benedikt; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Northcott, Paul A; Taylor, Michael D; Meyerson, Matthew; Pomeroy, Scott L; Yaspo, Marie-Laure; Korbel, Jan O; Korshunov, Andrey; Eils, Roland; Pfister, Stefan M; Lichter, Peter

2013-01-01

Summary Medulloblastoma is an aggressively-growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and displays tremendous biological and clinical heterogeneity1. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently discriminated2,3. WNT tumours, displaying activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens4. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis2. Group 3 & 4 tumours are molecularly less well-characterised, and also present the greatest clinical challenges2,3,5. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs. Tetraploidy was identified as a frequent early event in Group 3 & 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA-sequencing confirmed these alterations, and revealed the expression of the first medulloblastoma fusion genes. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 & 4 patients. PMID:22832583

A computational study of anion-modulated cation-π interactions.

PubMed

Carrazana-García, Jorge A; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

2012-05-24

The interaction of anions with cation-π complexes formed by the guanidinium cation and benzene was thoroughly studied by means of computational methods. Potential energy surface scans were performed in order to evaluate the effect of the anion coming closer to the cation-π pair. Several structures of guanidinium-benzene complexes and anion approaching directions were examined. Supermolecule calculations were performed on ternary complexes formed by guanidinium, benzene, and one anion and the interaction energy was decomposed into its different two- and three-body contributions. The interaction energies were further dissected into their electrostatic, exchange, repulsion, polarization and dispersion contributions by means of local molecular orbital energy decomposition analysis. The results confirm that, besides the electrostatic cation-anion attraction, the effect of the anion over the cation-π interaction is mainly due to polarization and can be rationalized following the changes in the anion-π and the nonadditive (three-body) terms of the interaction. When the cation and the anion are on the same side of the π system, the three-body interaction is anticooperative, but when the anion and the cation are on opposite sides of the π system, the three-body interaction is cooperative. As far as we know, this is the first study where this kind of analysis is carried out with a structured cation as guanidinium with a significant biological interest.

Anatomic documentation of the G-spot complex role in the genesis of anterior vaginal wall ballooning.

PubMed

Ostrzenski, Adam

2014-09-01

To expand previous G-spot anatomical and histological investigations; to examine the G-spot complex anatomic role in the anterior vaginal wall ballooning bio-mechanisms; and to determine, which division of autonomic nervous system (sympathetic or parasympathetic) dominates at the time of female sudden death. A prospective-descriptive case series anatomical study on eleven consecutive fresh humane female cadavers was conducted. Anterior vaginal wall stratum-by-stratum macro-dissections were executed in axial, coronal and sagittal plains. Upon G-spot extirpations, micro-dissections were performed. The G-spot tissues were stained with hematoxilin and eosin for histological examinations to authenticate the G-spot anatomical and histological characteristic features. The G-spot complex was identified and present in all subjects on either the distal vaginal left (more often) or on the right side from the lateral margin of the urethra; the G-spot anatomical and microscopic characteristic features have been authenticated; the G-spot complex expansion elevated anterior vaginal walls in each subject; the autonomic parasympathetic nervous system was the dominant division at the time of female subject sudden death. This study advances our anatomical and histological understanding of the G-spot complex and its role in the genesis of anterior vaginal ballooning bio-mechanisms. The G-spot complex is under parasympathetic nervous system domination at the time of female sudden death. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Discussion on standardized implementation of laparoscopic radical lymphadenectomy for distal gastric cancer].

PubMed

Lyu, Zejian; Wang, Junjiang; Li, Yong

2017-08-25

Laparoscopic radical gastrectomy for gastric cancer has been widely applied in clinical practice, and its indications have been extended from early gastric cancer to advanced gastric cancer. It is acknowledged that laparoscopic radical gastrectomy is technically challenging because of the complexity of anatomy, rich blood supply, and extensive lymph node dissection. This paper primarily intends to share the experience of laparoscopic radical D2 gastrectomy for distal gastric cancer with details of choosing the location of Trocar, surgical approaches and the sequence of lymph node dissection. All the surgeries were performed at Department of General Surgery and Gastrointestinal Surgery, Guangdong General Hospital. The finding suggests that a correct laparoscopic Trocar placement is the foundation of adequate surgical field visualization. Under most circumstances, the observation hole should be around 2 cm below the umbilicus and the operating hole should be close to the bilateral clavicle midline. Furthermore, proper surgical approach and sequence of lymph node dissection are the prerequisites for successful laparoscopic radical D2 gastrectomy, as well as the reassurance of dissecting lymph node safely and comprehensively. The position of surgical team adopted in our center is that the surgeon stands to the left of the patient, with laparoscope operator stands in between patient's legs while the first assistant positions himself opposite the surgeon on the right side of the patient. This position correlates to the rules of sequential lymph node dissection, which is "from left to right", "from proximal to distal" and "from inferior to superior". Therefore, it is conductive to inferior and superior pylorus region dissection and it can effectively prevent subsidiary-injury. In our center, the procedure of lymph node dissection has been standardized: the initial step is to undergo station 4sb dissection and greater gastric curvature clearance; then change the patient's position to clean the sub-pyloric lymph node region and cut off the duodenum by linear stapler; followed by the clearance of inferior region of the pylorus and the upper margin of the pancreas; in the final step, the first and the third groups of lymph node dissection is performed. Although varied surgical approaches and sequences of lymph node dissection are applied in different hospitals, the techniques required for laparoscopic D2 radical gastrectomy for gastric cancer are sophisticated and advanced in general. Radical lymph node dissection is complicated, urging surgeons to familiarize themselves with the anatomy of gastric peripheral vascular system and characteristics of lymph node drainage. By designing and implementing effective strategies, such as formulating a regular team, positioning surgical team reasonably, changing a patient's posture during operation, choosing an appropriate surgical approach and following a logically sequence of lymph node dissection, surgeons can standardize the complete surgical procedure, which ultimately reduces bleeding during surgery and shortens the operative time.

Dissecting repulsion linkage in the dwarfing gene Dw3 region for sorghum plant height provides insights into heterosis.

PubMed

Li, Xin; Li, Xianran; Fridman, Eyal; Tesso, Tesfaye T; Yu, Jianming

2015-09-22

Heterosis is a main contributor to yield increase in many crop species. Different mechanisms have been proposed for heterosis: dominance, overdominance, epistasis, epigenetics, and protein metabolite changes. However, only limited examples of molecular dissection and validation of these mechanisms are available. Here, we present an example of discovery and validation of heterosis generated by a combination of repulsion linkage and dominance. Using a recombinant inbred line population, a separate quantitative trait locus (QTL) for plant height (qHT7.1) was identified near the genomic region harboring the known auxin transporter Dw3 gene. With two loci having repulsion linkage between two inbreds, heterosis in the hybrid can appear as a single locus with an overdominance mode of inheritance (i.e., pseudo-overdominance). Individually, alleles conferring taller plant height exhibited complete dominance over alleles conferring shorter height. Detailed analyses of different height components demonstrated that qHT7.1 affects both the upper and lower parts of the plant, whereas Dw3 affects only the part below the flag leaf. Computer simulations show that repulsion linkage could influence QTL detection and estimation of effect in segregating populations. Guided by findings in linkage mapping, a genome-wide association study of plant height with a sorghum diversity panel pinpointed genomic regions underlying the trait variation, including Dw1, Dw2, Dw3, Dw4, and qHT7.1. Multilocus mixed model analysis confirmed the advantage of complex trait dissection using an integrated approach. Besides identifying a specific genetic example of heterosis, our research indicated that integrated molecular dissection of complex traits in different population types can enable plant breeders to fine tune the breeding process for crop production.

The pubovesical complex-sparing technique on laparoscopic radical prostatectomy.

PubMed

Rebouças, Rafael Batista; Monteiro, Rodrigo Campos; Lima, João Paulo Pereira; Almeida, Filipe Pádua B F; Britto, Cesar Araujo; Tobias-Machado, Marcos; Passerotti, Carlo

2018-03-01

Preservation of urinary continence is a great challenge in Radical Prostatectomy. In order to improve functional results, Asimakopoulos et al. (2010) described a robot-assisted surgical technique with preservation of the pubovesical complex (PVC). We present a pure laparoscopic execution. A 61-year-old male patient with a diagnosis of prostate cancer, with PSA 6.54ng/ml, DRE: T1C and Gleason 6 (3+3) 1/12 fragments. All therapeutic possibilities were discussed, including active surveillance. The patient opted for surgical treatment. A transperitoneal technique was used. We started the dissection on the left side, in the limit between the detrusor and the base of the prostate. The left seminal vesicle was dissected and left neurovascular bundle released by a high anterior dissection. We repeated the same procedure on the right side. The urethra was then divided, prostatic apex was laterally drawn and PVC was released. The bladder neck was divided and an urethrovesical anastomosis was achieved. A pelvic drain was placed. The total operative time was 150 minutes. The estimated blood loss was 300mL. The drain was removed on the 1st postoperative day and the patient was discharged. The Foley catheter was removed after 7 days and the patient remained completely dry. Hystopathology revealed adenocarcinoma Gleason 6, negative margins. PSA after 30 days was <0.04ng/mL, and the patient reported partial penile erection. The Pubovesical Complex-Sparing Technique on Laparoscopic Radical Prostatectomy was feasible and safe. Further adequately designed studies are needed to confirm whether this technique enhances early functional outcomes. Copyright® by the International Brazilian Journal of Urology.

Regulation of Lipid Metabolism by Dicer Revealed through SILAC Mice

PubMed Central

Huang, Tai-Chung; Saharabuddhe, Nandini A.; Kim, Min-Sik; Getnet, Derese; Yang, Yi; Peterson, Jonathan M.; Ghosh, Bidyut; Chaerkady, Raghothama; Leach, Steven D.; Marchionni, Luigi; Wong, G. William; Pandey, Akhilesh

2012-01-01

Dicer is a ribonuclease whose major role is to generate mature microRNAs although additional functions have been proposed. Deletion of Dicer leads to embryonic lethality in mice. To study the role of Dicer in adults, we generated mice in which administration of tamoxifen induces deletion of Dicer. Surprisingly, disruption of Dicer in adult mice induced lipid accumulation in the small intestine. To dissect the underlying mechanisms, we carried out miRNA, mRNA and proteomic profiling of small intestine. The proteomic analysis was done using mice metabolically labeled with heavy lysine (SILAC mice) for an in vivo readout. We identified 646 proteins of which 80 were upregulated >2-fold and 75 were downregulated. Consistent with the accumulation of lipids, Dicer disruption caused a marked decrease of microsomal triglyceride transfer protein, long-chain fatty acyl-CoA ligase 5, fatty acid binding protein, and very-long-chain fatty acyl-CoA dehydrogenase, among others. We validated these results using multiple reaction monitoring (MRM) experiments by targeting proteotypic peptides. Our data reveal a previously unappreciated role of Dicer in lipid metabolism. These studies demonstrate a systems biology approach by integrating mouse models, metabolic labeling, gene expression profiling and quantitative proteomics can be a powerful tool for understanding complex biological systems. PMID:22313051

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

PubMed Central

Asher, Tedi E.; Wilson, Nancy A.; Nason, Martha C.; Brenchley, Jason M.; Metzler, Ian S.; Venturi, Vanessa; Gostick, Emma; Chattopadhyay, Pratip K.; Roederer, Mario; Davenport, Miles P.; Watkins, David I.; Douek, Daniel C.

2009-01-01

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection. PMID:19349463

Protein Structure Initiative Material Repository: an open shared public resource of structural genomics plasmids for the biological community

PubMed Central

Cormier, Catherine Y.; Mohr, Stephanie E.; Zuo, Dongmei; Hu, Yanhui; Rolfs, Andreas; Kramer, Jason; Taycher, Elena; Kelley, Fontina; Fiacco, Michael; Turnbull, Greggory; LaBaer, Joshua

2010-01-01

The Protein Structure Initiative Material Repository (PSI-MR; http://psimr.asu.edu) provides centralized storage and distribution for the protein expression plasmids created by PSI researchers. These plasmids are a resource that allows the research community to dissect the biological function of proteins whose structures have been identified by the PSI. The plasmid annotation, which includes the full length sequence, vector information and associated publications, is stored in a freely available, searchable database called DNASU (http://dnasu.asu.edu). Each PSI plasmid is also linked to a variety of additional resources, which facilitates cross-referencing of a particular plasmid to protein annotations and experimental data. Plasmid samples can be requested directly through the website. We have also developed a novel strategy to avoid the most common concern encountered when distributing plasmids namely, the complexity of material transfer agreement (MTA) processing and the resulting delays this causes. The Expedited Process MTA, in which we created a network of institutions that agree to the terms of transfer in advance of a material request, eliminates these delays. Our hope is that by creating a repository of expression-ready plasmids and expediting the process for receiving these plasmids, we will help accelerate the accessibility and pace of scientific discovery. PMID:19906724

DGCA: A comprehensive R package for Differential Gene Correlation Analysis.

PubMed

McKenzie, Andrew T; Katsyv, Igor; Song, Won-Min; Wang, Minghui; Zhang, Bin

2016-11-15

Dissecting the regulatory relationships between genes is a critical step towards building accurate predictive models of biological systems. A powerful approach towards this end is to systematically study the differences in correlation between gene pairs in more than one distinct condition. In this study we develop an R package, DGCA (for Differential Gene Correlation Analysis), which offers a suite of tools for computing and analyzing differential correlations between gene pairs across multiple conditions. To minimize parametric assumptions, DGCA computes empirical p-values via permutation testing. To understand differential correlations at a systems level, DGCA performs higher-order analyses such as measuring the average difference in correlation and multiscale clustering analysis of differential correlation networks. Through a simulation study, we show that the straightforward z-score based method that DGCA employs significantly outperforms the existing alternative methods for calculating differential correlation. Application of DGCA to the TCGA RNA-seq data in breast cancer not only identifies key changes in the regulatory relationships between TP53 and PTEN and their target genes in the presence of inactivating mutations, but also reveals an immune-related differential correlation module that is specific to triple negative breast cancer (TNBC). DGCA is an R package for systematically assessing the difference in gene-gene regulatory relationships under different conditions. This user-friendly, effective, and comprehensive software tool will greatly facilitate the application of differential correlation analysis in many biological studies and thus will help identification of novel signaling pathways, biomarkers, and targets in complex biological systems and diseases.

Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

PubMed Central

Sunden, Fanny; Peck, Ariana; Salzman, Julia; Ressl, Susanne; Herschlag, Daniel

2015-01-01

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes. DOI: http://dx.doi.org/10.7554/eLife.06181.001 PMID:25902402

A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells.

PubMed

Ly, Tony; Ahmad, Yasmeen; Shlien, Adam; Soroka, Dominique; Mills, Allie; Emanuele, Michael J; Stratton, Michael R; Lamond, Angus I

2014-01-01

Technological advances have enabled the analysis of cellular protein and RNA levels with unprecedented depth and sensitivity, allowing for an unbiased re-evaluation of gene regulation during fundamental biological processes. Here, we have chronicled the dynamics of protein and mRNA expression levels across a minimally perturbed cell cycle in human myeloid leukemia cells using centrifugal elutriation combined with mass spectrometry-based proteomics and RNA-Seq, avoiding artificial synchronization procedures. We identify myeloid-specific gene expression and variations in protein abundance, isoform expression and phosphorylation at different cell cycle stages. We dissect the relationship between protein and mRNA levels for both bulk gene expression and for over ∼6000 genes individually across the cell cycle, revealing complex, gene-specific patterns. This data set, one of the deepest surveys to date of gene expression in human cells, is presented in an online, searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/). DOI: http://dx.doi.org/10.7554/eLife.01630.001.

Molecular regulation of plant cell wall extensibility

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1998-01-01

Gravity responses in plants often involve spatial and temporal changes in cell growth, which is regulated primarily by controlling the ability of the cell wall to extend. The wall is thought to be a cellulose-hemicellulose network embedded in a hydrated matrix of complex polysaccharides and a small amount of structural protein. The wall extends by a form of polymer creep, which is mediated by expansins, a novel group of wall-loosening proteins. Expansins were discovered during a molecular dissection of the "acid growth" behavior of cell walls. Expansin alters the rheology of plant walls in profound ways, yet its molecular mechanism of action is still uncertain. It lacks detectable hydrolytic activity against the major components of the wall, but it is able to disrupt noncovalent adhesion between wall polysaccharides. The discovery of a second family of expansins (beta-expansins) sheds light on the biological role of a major group of pollen allergens and implies that expansins have evolved for diverse developmental functions. Finally, the contribution of other processes to wall extensibility is briefly summarized.

A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells

PubMed Central

Ly, Tony; Ahmad, Yasmeen; Shlien, Adam; Soroka, Dominique; Mills, Allie; Emanuele, Michael J; Stratton, Michael R; Lamond, Angus I

2014-01-01

Technological advances have enabled the analysis of cellular protein and RNA levels with unprecedented depth and sensitivity, allowing for an unbiased re-evaluation of gene regulation during fundamental biological processes. Here, we have chronicled the dynamics of protein and mRNA expression levels across a minimally perturbed cell cycle in human myeloid leukemia cells using centrifugal elutriation combined with mass spectrometry-based proteomics and RNA-Seq, avoiding artificial synchronization procedures. We identify myeloid-specific gene expression and variations in protein abundance, isoform expression and phosphorylation at different cell cycle stages. We dissect the relationship between protein and mRNA levels for both bulk gene expression and for over ∼6000 genes individually across the cell cycle, revealing complex, gene-specific patterns. This data set, one of the deepest surveys to date of gene expression in human cells, is presented in an online, searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/). DOI: http://dx.doi.org/10.7554/eLife.01630.001 PMID:24596151

Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

DOE PAGES

Sunden, Fanny; Peck, Ariana; Salzman, Julia; ...

2015-04-22

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modesmore » of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes.« less

[Bardet-Biedl syndrome: cilia and obesity - from genes to integrative approaches].

PubMed

Chennen, Kirsley; Scerbo, Maria Julia; Dollfus, Hélène; Poch, Olivier; Marion, Vincent

2014-11-01

The primary cilium is a specialized organelle, present at the surface of most eukaryotic cells, whose main function is to detect, integrate and transmit intra- and extra-cellular signals. Its dysfunction usually results in a group of severe clinical manifestations nowadays termed ciliopathies. The latter can be of syndromic nature with multi-organ dysfunctions and can also be associated with a morbid obese phenotype, like it is the case in the iconic ciliopathy, the Bardet Biedl syndrome (BBS). This review will discuss the contribution of the unique context offered by the emblematic BBS for understanding the mechanisms leading to obesity via the involvement of the primary cilium together with identification of novel molecular players and signaling pathways it has helped to highlight. In the current context of translational medicine and system biology, this article will also discuss the potential benefits and challenges posed by these techniques via multi-level approaches to better dissect the underlying mechanisms leading to the complex condition of obesity. © 2014 médecine/sciences – Inserm.

Local Geometry and Evolutionary Conservation of Protein Surfaces Reveal the Multiple Recognition Patches in Protein-Protein Interactions

PubMed Central

Laine, Elodie; Carbone, Alessandra

2015-01-01

Protein-protein interactions (PPIs) are essential to all biological processes and they represent increasingly important therapeutic targets. Here, we present a new method for accurately predicting protein-protein interfaces, understanding their properties, origins and binding to multiple partners. Contrary to machine learning approaches, our method combines in a rational and very straightforward way three sequence- and structure-based descriptors of protein residues: evolutionary conservation, physico-chemical properties and local geometry. The implemented strategy yields very precise predictions for a wide range of protein-protein interfaces and discriminates them from small-molecule binding sites. Beyond its predictive power, the approach permits to dissect interaction surfaces and unravel their complexity. We show how the analysis of the predicted patches can foster new strategies for PPIs modulation and interaction surface redesign. The approach is implemented in JET2, an automated tool based on the Joint Evolutionary Trees (JET) method for sequence-based protein interface prediction. JET2 is freely available at www.lcqb.upmc.fr/JET2. PMID:26690684

Understand the cogs to understand cognition.

PubMed

Marblestone, Adam H; Wayne, Greg; Kording, Konrad P

2017-01-01

Lake et al. suggest that current AI systems lack the inductive biases that enable human learning. However, Lake et al.'s proposed biases may not directly map onto mechanisms in the developing brain. A convergence of fields may soon create a correspondence between biological neural circuits and optimization in structured architectures, allowing us to systematically dissect how brains learn.

The Influence of Perceived Disgust on Students' Motivation and Achievement

ERIC Educational Resources Information Center

Randler, Christoph; Hummel, Eberhard; Wüst-Ackermann, Peter

2013-01-01

There are a wide range of student emotions in academic settings, but apart from emotions such as interest and well-being, disgust is a negative emotion which might be relevant in biology education, for instance, during dissection or when encountering living animals. This paper addresses the issue of situational disgust during a course at the…

Animals from the Outside In, Science (Experimental): 5314.01.

ERIC Educational Resources Information Center

Kleinman, David Z.

Presented is an outline of a basic course (low level) in biology for students whose interest and background are very limited. The study and dissection of earthworm, crayfish, perch, and bird are included. A detailed study of the frog is undertaken as a representative of the animal kingdom. Performance objectives are presented, as well as a course…

Surveillance Cameras and Their Use as a Dissecting Microscope in the Teaching of Biological Sciences

ERIC Educational Resources Information Center

Vale, Marcus R.

2016-01-01

Surveillance cameras are prevalent in various public and private areas, and they can also be coupled to optical microscopes and telescopes with excellent results. They are relatively simple cameras without sophisticated technological features and are much less expensive and more accessible to many people. These features enable them to be used in…

Mutation at the TrkB PLC[gamma]-Docking Site Affects Hippocampal LTP and Associative Learning in Conscious Mice

ERIC Educational Resources Information Center

Valenzuela-Harrington, Mauricio; Delgado-Garcia, Jose M.; Minichiello, Liliana; Gruart, Agnes; Sciarretta, Carla

2007-01-01

Previous in vitro studies have characterized the electrophysiological properties and molecular events associated with long-term potentiation (LTP), but as yet there are no in vivo data from molecular-level dissection that directly identify LTP as the biological substrate for learning and memory. Understanding whether the molecular pathways…

miR-142-3p is involved in CD25+ CD4 T cell proliferation by targeting the expression of glycoprotein A repetitions predominant.

PubMed

Zhou, Qihui; Haupt, Sonja; Prots, Iryna; Thümmler, Katja; Kremmer, Elisabeth; Lipsky, Peter E; Schulze-Koops, Hendrik; Skapenko, Alla

2013-06-15

Because of the numerous targets of microRNAs (miRNAs), functional dissection of specific miRNA/mRNA interactions is important to understand the complex miRNA regulatory mechanisms. Glycoprotein A repetitions predominant (GARP) is specifically expressed on regulatory CD25(+) CD4 T cells upon their activation. GARP has a long 3' untranslated region containing five highly conserved regions suggesting miRNA regulation of its expression. Although GARP is physiologically expressed on a cell subset characterized by stringent control of proliferation, amplification of the GARP gene has been found in many tumors characterized by uncontrolled proliferation. In this study, we investigated in detail miRNA regulation of GARP expression, in particular by miR-142-3p, and dissected the functional outcome of miR-142-3p/GARP mRNA interaction. We demonstrate that miR-142-3p binds directly to the 3' untranslated region of GARP and represses GARP protein expression by Argonaute 2-associated degradation of GARP mRNA. Functionally, miR-142-3p-mediated regulation of GARP is involved in the expansion of CD25(+) CD4 T cells in response to stimulation. The data indicate that miR-142-3p regulates GARP expression on CD25(+) CD4 T cells and, as a result, their expansion in response to activation. Our data provide novel insight into the molecular mechanisms controlling regulatory T cell expansion. They may also have implications for understanding tumor cell biology.

Dissecting Low Atmospheric Pressure Stress: Transcriptome Responses to the Components of Hypobaria in Arabidopsis

PubMed Central

Zhou, Mingqi; Callaham, Jordan B.; Reyes, Matthew; Stasiak, Michael; Riva, Alberto; Zupanska, Agata K.; Dixon, Mike A.; Paul, Anna-Lisa; Ferl, Robert J.

2017-01-01

Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology, yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude, for example, presents terrestrial hypobaria always with hypoxia as a component stress, since the relative partial pressure of O2 is constant in the atmosphere. Laboratory-controlled hypobaria, however, allows the dissection of pressure effects away from the effects typically associated with altitude, in particular hypoxia, as the partial pressure of O2 can be varied. In this study, whole transcriptomes of plants grown in ambient (97 kPa/pO2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO2 = 10 kPa, 25 kPa/pO2 = 5 kPa, 50 kPa/pO2 = 21 kPa, 25 kPa/pO2 = 21 kPa, or 97 kPa/pO2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition, 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia, and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses. PMID:28443120

Dissecting Low Atmospheric Pressure Stress: Transcriptome Responses to the Components of Hypobaria in Arabidopsis.

PubMed

Zhou, Mingqi; Callaham, Jordan B; Reyes, Matthew; Stasiak, Michael; Riva, Alberto; Zupanska, Agata K; Dixon, Mike A; Paul, Anna-Lisa; Ferl, Robert J

2017-01-01

Controlled hypobaria presents biology with an environment that is never encountered in terrestrial ecology, yet the apparent components of hypobaria are stresses typical of terrestrial ecosystems. High altitude, for example, presents terrestrial hypobaria always with hypoxia as a component stress, since the relative partial pressure of O 2 is constant in the atmosphere. Laboratory-controlled hypobaria, however, allows the dissection of pressure effects away from the effects typically associated with altitude, in particular hypoxia, as the partial pressure of O 2 can be varied. In this study, whole transcriptomes of plants grown in ambient (97 kPa/pO 2 = 21 kPa) atmospheric conditions were compared to those of plants transferred to five different atmospheres of varying pressure and oxygen composition for 24 h: 50 kPa/pO 2 = 10 kPa, 25 kPa/pO 2 = 5 kPa, 50 kPa/pO 2 = 21 kPa, 25 kPa/pO 2 = 21 kPa, or 97 kPa/pO 2 = 5 kPa. The plants exposed to these environments were 10 day old Arabidopsis seedlings grown vertically on hydrated nutrient plates. In addition, 5 day old plants were also exposed for 24 h to the 50 kPa and ambient environments to evaluate age-dependent responses. The gene expression profiles from roots and shoots showed that the hypobaric response contained more complex gene regulation than simple hypoxia, and that adding back oxygen to normoxic conditions did not completely alleviate gene expression changes in hypobaric responses.

Asymmetric configurations in a reengineered homodimer reveal multiple subunit communication pathways in protein allostery

PubMed Central

Lanfranco, Maria Fe; Gárate, Fernanda; Engdahl, Ashton J.; Maillard, Rodrigo A.

2017-01-01

Many allosteric proteins form homo-oligomeric complexes to regulate a biological function. In homo-oligomers, subunits establish communication pathways that are modulated by external stimuli like ligand binding. A challenge for dissecting the communication mechanisms in homo-oligomers is identifying intermediate liganded states, which are typically transiently populated. However, their identities provide the most mechanistic information on how ligand-induced signals propagate from bound to empty subunits. Here, we dissected the directionality and magnitude of subunit communication in a reengineered single-chain version of the homodimeric transcription factor cAMP receptor protein. By combining wild-type and mutant subunits in various asymmetric configurations, we revealed a linear relationship between the magnitude of cooperative effects and the number of mutant subunits. We found that a single mutation is sufficient to change the global allosteric behavior of the dimer even when one subunit was wild type. Dimers harboring two mutations with opposite cooperative effects had different allosteric properties depending on the arrangement of the mutations. When the two mutations were placed in the same subunit, the resulting cooperativity was neutral. In contrast, when placed in different subunits, the observed cooperativity was dominated by the mutation with strongest effects over cAMP affinity relative to wild type. These results highlight the distinct roles of intrasubunit interactions and intersubunit communication in allostery. Finally, dimers bound to either one or two cAMP molecules had similar DNA affinities, indicating that both asymmetric and symmetric liganded states activate DNA interactions. These studies have revealed the multiple communication pathways that homo-oligomers employ to transduce signals. PMID:28188293

Affinity proteomics to study endogenous protein complexes: Pointers, pitfalls, preferences and perspectives

PubMed Central

LaCava, John; Molloy, Kelly R.; Taylor, Martin S.; Domanski, Michal; Chait, Brian T.; Rout, Michael P.

2015-01-01

Dissecting and studying cellular systems requires the ability to specifically isolate distinct proteins along with the co-assembled constituents of their associated complexes. Affinity capture techniques leverage high affinity, high specificity reagents to target and capture proteins of interest along with specifically associated proteins from cell extracts. Affinity capture coupled to mass spectrometry (MS)-based proteomic analyses has enabled the isolation and characterization of a wide range of endogenous protein complexes. Here, we outline effective procedures for the affinity capture of protein complexes, highlighting best practices and common pitfalls. PMID:25757543

The function and evolution of male and female genitalia in Phyllophaga Harris scarab beetles (Coleoptera: Scarabaeidae).

PubMed

Richmond, M P; Park, J; Henry, C S

2016-11-01

Genitalia diversity in insects continues to fuel investigation of the function and evolution of these dynamic structures. Whereas most studies have focused on variation in male genitalia, an increasing number of studies on female genitalia have uncovered comparable diversity among females, but often at a much finer morphological scale. In this study, we analysed the function and evolution of male and female genitalia in Phyllophaga scarab beetles, a group in which both sexes exhibit genitalic diversity. To document the interaction between male and female structures during mating, we dissected flash-frozen mating pairs from three Phyllophaga species and investigated fine-scale morphology using SEM. We then reconstructed ancestral character states using a species tree inferred from mitochondrial and nuclear loci to elucidate and compare the evolutionary history of male and female genitalia. Our dissections revealed an interlocking mechanism of the female pubic process and male parameres that appears to improve the mechanical fit of the copulatory position. The comparative analyses, however, did not support coevolution of male and female structures and showed more erratic evolution of the female genitalia relative to males. By studying a group that exhibits obvious female genitalic diversity, we were able to demonstrate the relevance of female reproductive morphology in studies of male genital diversity. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

How can we deal with mental distress in the dissection room?-An evaluation of the need for psychological support.

PubMed

Boeckers, Anja; Brinkmann, Anke; Jerg-Bretzke, Lucia; Lamp, Christoph; Traue, Harald C; Boeckers, Tobias M

2010-12-20

The dissection course (DC) is an essential part of the preclinical medical curriculum that mediates professionalism. The process of dissecting, however, has an inherent additional stress potential. Our study determined student mental stress, their need of psychological support and factors influencing this need. A quantitative longitudinal query before, during and after the DC was performed including the Brief Symptom Inventory (BSI) as well as self-formulated questions used a 5-point Likert scale. Half of the students who anticipated dissection to be a stress factor reported that this declined significantly over time. Instead, student fear of not being able to cope with the work load increased significantly. As many as 64% of the students favored psychological support on the first course day, while 75% rejected this during the period of dissection and 39% appreciated this after the course. Moreover, 42% emphasized the importance of the funeral ceremony. Additionally, 75% documented their need for support in coping with stress and learning strategies. Gender, previous medical training, and BSI levels were identified as psychosocial influence factors. A majority of students named friends, members of their family or workmates as partners with whom they could talk about mental stress. Our results document the need to develop an optimum support during the DC taking into account the ascertained indicators. Exemplarily the Institute of Anatomy and Cell Biology at Ulm University suggests several options like a step by step approach for optimization. These measures reduce mental stress and help students to cope with it by the development of "detached concern" towards their "first patient" as this will decisively influence their future professional behavior. 2010 Elsevier GmbH. All rights reserved.

Genetic Dissection of Learning and Memory in Mice

PubMed Central

Mineur, Yann S.; Crusio, Wim E.; Sluyter, Frans

2004-01-01

In this minireview, we discuss different strategies to dissect genetically the keystones of learning and memory. First, we broadly sketch the neurogenetic analysis of complex traits in mice. We then discuss two general strategies to find genes affecting learning and memory: candidate gene studies and whole genome searches. Next, we briefly review more recently developed techniques, such as microarrays and RNA interference. In addition, we focus on gene-environment interactions and endophenotypes. All sections are illustrated with examples from the learning and memory field, including a table summarizing the latest information about genes that have been shown to have effects on learning and memory. PMID:15656270

Aortic dissection simulation models for clinical support: fluid-structure interaction vs. rigid wall models.

PubMed

Alimohammadi, Mona; Sherwood, Joseph M; Karimpour, Morad; Agu, Obiekezie; Balabani, Stavroula; Díaz-Zuccarini, Vanessa

2015-04-15

The management and prognosis of aortic dissection (AD) is often challenging and the use of personalised computational models is being explored as a tool to improve clinical outcome. Including vessel wall motion in such simulations can provide more realistic and potentially accurate results, but requires significant additional computational resources, as well as expertise. With clinical translation as the final aim, trade-offs between complexity, speed and accuracy are inevitable. The present study explores whether modelling wall motion is worth the additional expense in the case of AD, by carrying out fluid-structure interaction (FSI) simulations based on a sample patient case. Patient-specific anatomical details were extracted from computed tomography images to provide the fluid domain, from which the vessel wall was extrapolated. Two-way fluid-structure interaction simulations were performed, with coupled Windkessel boundary conditions and hyperelastic wall properties. The blood was modelled using the Carreau-Yasuda viscosity model and turbulence was accounted for via a shear stress transport model. A simulation without wall motion (rigid wall) was carried out for comparison purposes. The displacement of the vessel wall was comparable to reports from imaging studies in terms of intimal flap motion and contraction of the true lumen. Analysis of the haemodynamics around the proximal and distal false lumen in the FSI model showed complex flow structures caused by the expansion and contraction of the vessel wall. These flow patterns led to significantly different predictions of wall shear stress, particularly its oscillatory component, which were not captured by the rigid wall model. Through comparison with imaging data, the results of the present study indicate that the fluid-structure interaction methodology employed herein is appropriate for simulations of aortic dissection. Regions of high wall shear stress were not significantly altered by the wall motion, however, certain collocated regions of low and oscillatory wall shear stress which may be critical for disease progression were only identified in the FSI simulation. We conclude that, if patient-tailored simulations of aortic dissection are to be used as an interventional planning tool, then the additional complexity, expertise and computational expense required to model wall motion is indeed justified.

Neurofibromatosis of the head and neck: classification and surgical management.

PubMed

Latham, Kerry; Buchanan, Edward P; Suver, Daniel; Gruss, Joseph S

2015-03-01

Neurofibromatosis is common and presents with variable penetrance and manifestations in one in 2500 to one in 3000 live births. The management of these patients is often multidisciplinary because of the complexity of the disease. Plastic surgeons are frequently involved in the surgical management of patients with head and neck involvement. A 20-year retrospective review of patients treated surgically for head and neck neurofibroma was performed. Patients were identified according to International Classification of Diseases, Ninth Revision codes for neurofibromatosis and from the senior author's database. A total of 59 patients with head and neck neurofibroma were identified. These patients were categorized into five distinct, but not exclusive, categories to assist with diagnosis and surgical management. These categories included plexiform, cranioorbital, facial, neck, and parotid/auricular neurofibromatosis. A surgical classification system and clinical characteristics of head and neck neurofibromatosis is presented to assist practitioners with diagnosis and surgical management of this complex disease. The surgical management of the cranioorbital type is discussed in detail in 24 patients. The importance and safety of facial nerve dissection and preservation using intraoperative nerve monitoring were validated in 16 dissections in 15 patients. Massive involvement of the neck extending from the skull base to the mediastinum, frequently considered inoperable, has been safely resected by the use of access osteotomies of the clavicle and sternum, muscle takedown, and brachial plexus dissection and preservation using intraoperative nerve monitoring. Therapeutic, IV.

Antigravity ESD - double-balloon-assisted underwater with traction hybrid technique.

PubMed

Sharma, Sam K; Hiratsuka, Takahiro; Hara, Hisashi; Milsom, Jeffrey W

2018-06-01

 Complex colorectal polyps or those positioned in difficult anatomic locations are an endoscopic therapeutic challenge. Underwater endoscopic submucosal dissection (UESD) is a potential technical solution to facilitate efficient polyp removal. In addition, endoscopic tissue retraction has been confined to limited methods of varying efficacy and complexity. The aim of this study was to evaluate the efficiency of a unique UESD technique for removing complex polyps using double-balloon-assisted retraction (R).  Using fresh ex-vivo porcine rectum, 4-cm polyps were created using electrosurgery and positioned at "6 o'clock" within an established ESD model. Six resections were performed in each group. Underwater techniques were facilitated using a novel double-balloon platform (Dilumen, Lumendi, Westport, Connecticut, United States).  UESD-R had a significantly shorter total procedural time than cap-assisted ESD and UESD alone (24 vs. 58 vs. 56 mins). UESD-R produced a dissection time on average of 5 minutes, attributed to the retraction provided. There was also a subjective significant reduction in electrosurgical smoke with the underwater techniques contributing to improved visualization.  Here we report the first ex-vivo experience of a unique double-balloon endoscopic platform optimized for UESD with tissue traction capability. UESD-R removed complex lesions in significantly shorter time than conventional means. The combined benefits of UESD and retraction appeared to be additive when tackling complex polyps and should be studied further.

Using Comparative Genomics for Inquiry-Based Learning to Dissect Virulence of "Escherichia coli" O157:H7 and "Yersinia pestis"

ERIC Educational Resources Information Center

Baumler, David J.; Banta, Lois M.; Hung, Kai F.; Schwarz, Jodi A.; Cabot, Eric L.; Glasner, Jeremy D.; Perna, Nicole T.

2012-01-01

Genomics and bioinformatics are topics of increasing interest in undergraduate biological science curricula. Many existing exercises focus on gene annotation and analysis of a single genome. In this paper, we present two educational modules designed to enable students to learn and apply fundamental concepts in comparative genomics using examples…

Casting materials and their application in research and teaching.

PubMed

Haenssgen, Kati; Makanya, Andrew N; Djonov, Valentin

2014-04-01

From a biological point of view, casting refers to filling of anatomical and/or pathological spaces with extraneous material that reproduces a three-dimensional replica of the space. Casting may be accompanied by additional procedures such as corrosion, in which the soft tissue is digested out, leaving a clean cast, or the material may be mixed with radiopaque substances to allow x-ray photography or micro computed topography (µCT) scanning. Alternatively, clearing of the surrounding soft tissue increases transparency and allows visualization of the casted cavities. Combination of casting with tissue fixation allows anatomical dissection and didactic surgical procedures on the tissue. Casting materials fall into three categories namely, aqueous substances (India ink, Prussian blue ink), pliable materials (gelatins, latex, and silicone rubber), or hard materials (methyl methacrylates, polyurethanes, polyesters, and epoxy resins). Casting has proved invaluable in both teaching and research and many phenomenal biological processes have been discovered through casting. The choice of a particular material depends inter alia on the targeted use and the intended subsequent investigative procedures, such as dissection, microscopy, or µCT. The casting material needs to be pliable where anatomical and surgical manipulations are intended, and capillary-passable for ultrastructural investigations.

GAPIT version 2: an enhanced integrated tool for genomic association and prediction

USDA-ARS?s Scientific Manuscript database

Most human diseases and agriculturally important traits are complex. Dissecting their genetic architecture requires continued development of innovative and powerful statistical methods. Corresponding advances in computing tools are critical to efficiently use these statistical innovations and to enh...

Dissection and Exposure of the Whole Course of Deep Nerves in Human Head Specimens after Decalcification

PubMed Central

Liu, Longping; Arnold, Robin; Robinson, Marcus

2012-01-01

The whole course of the chorda tympani nerve, nerve of pterygoid canal, and facial nerves and their relationships with surrounding structures are complex. After reviewing the literature, it was found that details of the whole course of these deep nerves are rarely reported and specimens displaying these nerves are rarely seen in the dissecting room, anatomical museum, or atlases. Dissections were performed on 16 decalcified human head specimens, exposing the chorda tympani and the nerve connection between the geniculate and pterygopalatine ganglia. Measurements of nerve lengths, branching distances, and ganglia size were taken. The chorda tympani is a very fine nerve (0.44 mm in diameter within the tympanic cavity) and approximately 54 mm in length. The mean length of the facial nerve from opening of internal acoustic meatus to stylomastoid foramen was 52.5 mm. The mean length of the greater petrosal nerve was 26.1 mm and nerve of the pterygoid canal was 15.1 mm. PMID:22523494

A new tool called DISSECT for analysing large genomic data sets using a Big Data approach

PubMed Central

Canela-Xandri, Oriol; Law, Andy; Gray, Alan; Woolliams, John A.; Tenesa, Albert

2015-01-01

Large-scale genetic and genomic data are increasingly available and the major bottleneck in their analysis is a lack of sufficiently scalable computational tools. To address this problem in the context of complex traits analysis, we present DISSECT. DISSECT is a new and freely available software that is able to exploit the distributed-memory parallel computational architectures of compute clusters, to perform a wide range of genomic and epidemiologic analyses, which currently can only be carried out on reduced sample sizes or under restricted conditions. We demonstrate the usefulness of our new tool by addressing the challenge of predicting phenotypes from genotype data in human populations using mixed-linear model analysis. We analyse simulated traits from 470,000 individuals genotyped for 590,004 SNPs in ∼4 h using the combined computational power of 8,400 processor cores. We find that prediction accuracies in excess of 80% of the theoretical maximum could be achieved with large sample sizes. PMID:26657010

Do frogs have to croak? Comparing academic performance of students in traditional dissection labs on campus with students using virtual simulations via distance education

NASA Astrophysics Data System (ADS)

Humphries, Susie Annette

This quantitative study was designed to determine whether there were any significant differences in students and their understanding of animal anatomy and basic physiology in introductory biology and anatomy courses when instructed using self-directed, virtual simulation dissections in a distance-learning format rather than by teacher-directed, hands-on dissections in traditional on-campus classes. Two different courses at Snead State Community College, a small, rural 2-year institution in north Alabama, participated in this study. Principles of Biology II (BIO 104) was a course taken by students not planning a career in a health field, while Human Anatomy and Physiology I (BIO 201) was a course designed for students who plan to pursue a health-related degree. A total of 44 students participated in the online versions of their respective anatomy courses, 11 in BIO 104 and 33 in BIO 201, whereas a total of 132 students participated in the on-campus versions of their anatomy courses, 28 in BIO 104 and 104 in BIO 201. At the outset of their anatomy courses, all participants were given a presurvey to obtain basic demographics and background information used in the final analyses. A pretest/posttest laboratory practicum evaluation was used to determine students' academic performance in their anatomy courses over a semester. The results indicated that for the BIO 104 students there were no significant differences between those students taking the course online and those taking the course on campus. The BIO 201 students, on the other hand, did indicate a significant difference in the overall academic performance on their laboratory practicums, with the on-campus students achieving statistically higher than the online students. However, it is important to note that the BIO 104 students were not taking their exams as a part of their course grade as were the BIO 201 students. It was also ascertained through this study that students with prior online experience and/or with moderate to substantial dissection experience did not perform statistically better than students without these experiences. Additionally, various characteristics and qualities associated with the success of students in anatomy courses were discovered.

Student learning style preferences in college-level biology courses: Implications for teaching and academic performance

NASA Astrophysics Data System (ADS)

Sitton, Jennifer Susan

Education research has focused on defining and identifying student learning style preferences and how to incorporate this knowledge into teaching practices that are effective in engaging student interest and transmitting information. One objective was determining the learning style preferences of undergraduate students in Biology courses at New Mexico State University by using the online VARK Questionnaire and an investigator developed survey (Self Assessed Learning Style Survey, LSS). Categories include visual, aural, read-write, kinesthetic, and multimodal. The courses differed in VARK single modal learning preferences (p = 0.035) but not in the proportions of the number of modes students preferred (p = 0.18). As elsewhere, the majority of students were multimodal. There were similarities and differences between LSS and VARK results and between students planning on attending medical school and those not. Preferences and modalities tended not to match as expected for ratings of helpfulness of images and text. To detect relationships between VARK preferred learning style and academic performance, ANOVAs were performed using modality preferences and normalized learning gains from pre and post tests over material taught in the different modalities, as well as on end of semester laboratory and lecture grades. Overall, preference did not affect the performance for a given modality based activity, quiz, or final lecture or laboratory grades (p > 0.05). This suggests that a student's preference does not predict an improved performance when supplied with material in that modality. It is recommended that methods be developed to aid learning in a variety of modalities, rather than catering to individual learning styles. Another topic that is heavily debated in the field of education is the use of simulations or videos to replace or supplement dissections. These activities were compared using normalized learning gains from pre and post tests, as well as attitude surveys. Results indicate no differences in average student learning gain based on the activity types tested, although students do rate dissections higher in terms of interest and enthusiasm. Dissections also offer a different type of learning. Therefore, it is suggested that simulations and videos be used as supplements for dissections and not as replacements.

TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis.

PubMed

Flutter, Barry; Nestle, Frank O

2013-12-01

Psoriasis is an inflammatory disease of the skin affecting 2-3% of the population, characterized by a thickening of the epidermis and immune infiltrates throughout the dermis and epidermis, causing skin lesions that can seriously affect quality of life. The study of psoriasis has historically been hampered by the lack of good animal models. Various genetically induced models exist, which have provided some information about possible mechanisms of disease, but these models rely mostly on intrinsic imbalances of homeostasis. However, a mouse model of psoriasiform dermatitis caused by the repeated topical application of Aldara™ containing 5% imiquimod was described in 2009. The mechanisms of action of Aldara™ are complex. Imiquimod is an effective ligand for TLR7 (and TLR8 in humans) and also interferes with adenosine receptor signaling. In addition, isostearic acid present in the Aldara™ vehicle has been shown to be biologically active and of importance for activating the inflammasome. Interestingly, the repetitive application of Aldara™ reveals a complex aetiology involving multiple cell types, cytokines, and inflammatory pathways. In this review, we will dissect the findings of the imiquimod model to date and ask how this model can inform us about the immunological aspects of human disease. © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

A global "imaging'' view on systems approaches in immunology.

PubMed

Ludewig, Burkhard; Stein, Jens V; Sharpe, James; Cervantes-Barragan, Luisa; Thiel, Volker; Bocharov, Gennady

2012-12-01

The immune system exhibits an enormous complexity. High throughput methods such as the "-omic'' technologies generate vast amounts of data that facilitate dissection of immunological processes at ever finer resolution. Using high-resolution data-driven systems analysis, causal relationships between complex molecular processes and particular immunological phenotypes can be constructed. However, processes in tissues, organs, and the organism itself (so-called higher level processes) also control and regulate the molecular (lower level) processes. Reverse systems engineering approaches, which focus on the examination of the structure, dynamics and control of the immune system, can help to understand the construction principles of the immune system. Such integrative mechanistic models can properly describe, explain, and predict the behavior of the immune system in health and disease by combining both higher and lower level processes. Moving from molecular and cellular levels to a multiscale systems understanding requires the development of methodologies that integrate data from different biological levels into multiscale mechanistic models. In particular, 3D imaging techniques and 4D modeling of the spatiotemporal dynamics of immune processes within lymphoid tissues are central for such integrative approaches. Both dynamic and global organ imaging technologies will be instrumental in facilitating comprehensive multiscale systems immunology analyses as discussed in this review. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An attachment-based description of the medial collateral and spring ligament complexes.

PubMed

Cromeens, Barrett P; Kirchhoff, Claire A; Patterson, Rita M; Motley, Travis; Stewart, Donald; Fisher, Cara; Reeves, Rustin E

2015-06-01

Anatomy of the medial collateral and spring ligament complexes has been the cause of confusion. The anatomic description is highly dependent on the source studied and little agreement exists between texts. In addition, inconsistent nomenclature has been used to describe the components. This study attempted to clarify confusion through the creation of a 3D ligament map using attachment-based dissection. Nine fresh foot and ankle specimens were observed. The medial collateral ligament and spring ligament complexes were dissected using their attachment sites as a guide to define individual components. Each component's perimeter and thickness was measured and each bony attachment was mapped using a microscribe 3D digitizer. Five components were identified contributing to the ligament complexes of interest: the tibiocalcaneonavicular, superficial posterior tibiotalar, deep posterior tibiotalar, deep anterior tibiotalar, and inferoplantar longitudinal ligaments. The largest component by total attachment area was the tibiocalcaneonavicular ligament followed by the deep posterior tibiotalar ligament. The largest ligament surface area of attachment to the tibia and talus was the deep posterior tibiotalar ligament. The largest attachment to the navicular and calcaneus was the tibiocalcaneonavicular ligament, which appeared to function in holding these bones in proximity while supporting the head of the talus. By defining complex components by their attachment sites, a novel, more functional and reproducible description of the medial collateral and spring ligament complexes was created. The linear measurements and 3D maps may prove useful when attempting more anatomically accurate reconstructions. © The Author(s) 2015.

Karolinska prostatectomy: a robot-assisted laparoscopic radical prostatectomy technique.

PubMed

Nilsson, Andreas E; Carlsson, Stefan; Laven, Brett A; Wiklund, N Peter

2006-01-01

The last decade has witnessed an increasing trend towards minimally invasive management of prostate cancer, including laparoscopic and, more recently, robot-assisted laparoscopic prostatectomy. Several different laparoscopic approaches have been continuously developed during the last 5 years and it is still unclear which technique yields the best outcome. We present our current technique of robot-assisted laparoscopic radical prostatectomy. The technique described has evolved during the course of >400 robotic prostatectomies performed by the robotic team since the robot-assisted laparoscopic radical prostatectomy program was introduced at Karolinska University Hospital in January 2002. Our procedure comprises several modifications of previously reported ones, and we utilize fewer robotic instruments to reduce costs. An extended posterior dissection is performed to aid in the bladder neck-sparing dissection. In nerve-sparing procedures the vesicles are divided to avoid damage to the erectile nerves. In order to preserve the apical anatomy the dorsal venous complex is incised sharply and is first over-sewn after the apical dissection is completed. Our technique enables a more fluent dissection than previously described robotic techniques. Minimizing changes of instruments and the camera not only cuts costs but also reduces inefficient operating maneuvers, such as switching between 30 degrees and 0 degrees lenses during the procedure. We present a technique which in our hands has achieved excellent functional and oncological results.

Genomic networks of hybrid sterility.

PubMed

Turner, Leslie M; White, Michael A; Tautz, Diethard; Payseur, Bret A

2014-02-01

Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities"). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics.

Genomic Networks of Hybrid Sterility

PubMed Central

Turner, Leslie M.; White, Michael A.; Tautz, Diethard; Payseur, Bret A.

2014-01-01

Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci (“Dobzhansky-Muller incompatibilities”). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL—but not cis eQTL—were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad range of organisms and we advocate for widespread adoption of a network-centered approach in speciation genetics. PMID:24586194

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

PubMed Central

Li, Xia; Rao, Shaoqi; Jiang, Wei; Li, Chuanxing; Xiao, Yun; Guo, Zheng; Zhang, Qingpu; Wang, Lihong; Du, Lei; Li, Jing; Li, Li; Zhang, Tianwen; Wang, Qing K

2006-01-01

Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs. PMID:16420705

Use of knowledge-sharing web-based portal in gross and microscopic anatomy.

PubMed

Durosaro, Olayemi; Lachman, Nirusha; Pawlina, Wojciech

2008-12-01

Changes in worldwide healthcare delivery require review of current medical school curricula structure to develop learning outcomes that ensures mastery of knowledge and clinical competency. In the last 3 years, Mayo Medical School implemented outcomes-based curriculum to encompass new graduate outcomes. Standard courses were replaced by 6-week clinically-integrated didactic blocks separated by student-self selected academic enrichment activities. Gross and microscopic anatomy was integrated with radiology and genetics respectively. Laboratory components include virtual microscopy and anatomical dissection. Students assigned to teams utilise computer portals to share learning experiences. High-resolution computed tomographic (CT) scans of cadavers prior to dissection were made available for correlative learning between the cadaveric material and radiologic images. Students work in teams on assigned presentations that include histology, cell and molecular biology, genetics and genomic using the Nexus Portal, based on DrupalEd, to share their observations, reflections and dissection findings. New generation of medical students are clearly comfortable utilising web-based programmes that maximise their learning potential of conceptually difficult and labor intensive courses. Team-based learning approach emphasising the use of knowledge-sharing computer portals maximises opportunities for students to master their knowledge and improve cognitive skills to ensure clinical competency.

Structural dissection of an interaction between transcription initiation and termination factors implicated in promoter-terminator cross-talk.

PubMed

Bratkowski, Matthew; Unarta, Ilona Christy; Zhu, Lizhe; Shubbar, Murtada; Huang, Xuhui; Liu, Xin

2018-02-02

Functional cross-talk between the promoter and terminator of a gene has long been noted. Promoters and terminators are juxtaposed to form gene loops in several organisms, and gene looping is thought to be involved in transcriptional regulation. The general transcription factor IIB (TFIIB) and the C-terminal domain phosphatase Ssu72, essential factors of the transcription preinitiation complex and the mRNA processing and polyadenylation complex, respectively, are important for gene loop formation. TFIIB and Ssu72 interact both genetically and physically, but the molecular basis of this interaction is not known. Here we present a crystal structure of the core domain of TFIIB in two new conformations that differ in the relative distance and orientation of the two cyclin-like domains. The observed extraordinary conformational plasticity may underlie the binding of TFIIB to multiple transcription factors and promoter DNAs that occurs in distinct stages of transcription, including initiation, reinitiation, and gene looping. We mapped the binding interface of the TFIIB-Ssu72 complex using a series of systematic, structure-guided in vitro binding and site-specific photocross-linking assays. Our results indicate that Ssu72 competes with acidic activators for TFIIB binding and that Ssu72 disrupts an intramolecular TFIIB complex known to impede transcription initiation. We also show that the TFIIB-binding site on Ssu72 overlaps with the binding site of symplekin, a component of the mRNA processing and polyadenylation complex. We propose a hand-off model in which Ssu72 mediates a conformational transition in TFIIB, accounting for the role of Ssu72 in transcription reinitiation, gene looping, and promoter-terminator cross-talk. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Dissecting the molecular assembly of the Toxoplasma gondii MyoA motility complex.

PubMed

Powell, Cameron J; Jenkins, Meredith L; Parker, Michelle L; Ramaswamy, Raghavendran; Kelsen, Anne; Warshaw, David M; Ward, Gary E; Burke, John E; Boulanger, Martin J

2017-11-24

Apicomplexan parasites such as Toxoplasma gondii rely on a unique form of locomotion known as gliding motility. Generating the mechanical forces to support motility are divergent class XIV myosins (MyoA) coordinated by accessory proteins known as light chains. Although the importance of the MyoA-light chain complex is well-established, the detailed mechanisms governing its assembly and regulation are relatively unknown. To establish a molecular blueprint of this dynamic complex, we first mapped the adjacent binding sites of light chains MLC1 and ELC1 on the MyoA neck (residues 775-818) using a combination of hydrogen-deuterium exchange mass spectrometry and isothermal titration calorimetry. We then determined the 1.85 Å resolution crystal structure of MLC1 in complex with its cognate MyoA peptide. Structural analysis revealed a bilobed architecture with MLC1 clamping tightly around the helical MyoA peptide, consistent with the stable 10 nm K d measured by isothermal titration calorimetry. We next showed that coordination of calcium by an EF-hand in ELC1 and prebinding of MLC1 to the MyoA neck enhanced the affinity of ELC1 for the MyoA neck 7- and 8-fold, respectively. When combined, these factors enhanced ELC1 binding 49-fold (to a K d of 12 nm). Using the full-length MyoA motor (residues 1-831), we then showed that, in addition to coordinating the neck region, ELC1 appears to engage the MyoA converter subdomain, which couples the motor domain to the neck. These data support an assembly model where staged binding events cooperate to yield high-affinity complexes that are able to maximize force transduction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Analytical Sociology: A Bungean Appreciation

ERIC Educational Resources Information Center

Wan, Poe Yu-ze

2012-01-01

Analytical sociology, an intellectual project that has garnered considerable attention across a variety of disciplines in recent years, aims to explain complex social processes by dissecting them, accentuating their most important constituent parts, and constructing appropriate models to understand the emergence of what is observed. To achieve…

Metagenomic Approaches to Investigate the Contribution of the Vineyard Environment to the Quality of Wine Fermentation: Potentials and Difficulties

PubMed Central

Stefanini, Irene; Cavalieri, Duccio

2018-01-01

The winemaking is a complex process that begins in the vineyard and ends at consumption moment. Recent reports have shown the relevance of microbial populations in the definition of the regional organoleptic and sensory characteristics of a wine. Metagenomic approaches, allowing the exhaustive identification of microorganisms present in complex samples, have recently played a fundamental role in the dissection of the contribution of the vineyard environment to wine fermentation. Systematic approaches have explored the impact of agronomical techniques, vineyard topologies, and climatic changes on bacterial and fungal populations found in the vineyard and in fermentations, also trying to predict or extrapolate the effects on the sensorial characteristics of the resulting wine. This review is aimed at highlighting the major technical and experimental challenges in dissecting the contribution of the vineyard and native environments microbiota to the wine fermentation process, and how metagenomic approaches can help in understanding microbial fluxes and selections across the environments and specimens related to wine fermentation. PMID:29867889

Primary mucosal sinonasal melanoma—Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy

PubMed Central

Marinova, Lena; Yordanov, Kaloyan; Sapundgiev, Nikolay

2010-01-01

Aim The place of adjuvant radiotherapy in the treatment of sinonasal melanoma. Background Sinonasal mucosal melanoma is a rare disease with poor prognosis and requires a complex treatment. Elective neck dissection in patients with N0 and adjuvant radiotherapy has been a source of controversy. High late regional recurrence rates rise questions about elective irradiation of the neck nodes in patients with N0 stage disease. Methods We present our two years’ follow up in a case of locally advanced sinonasal melanoma and literature review of the treatment options for mucosal melanoma. Results In locally advanced sinonasal melanoma treated with surgical resection, postoperative radiotherapy and chemotherapy we had local tumor control. Two years later, a regional contralateral recurrence without distant metastasis occurred. Conclusions Literature data for frequent neck lymph nodes recurrences justify elective neck dissection. Postoperative elective neck radiotherapy for patients with locally advanced sinonasal melanoma and clinically N0 appears to decrease the rate of late regional recurrences. PMID:24376954

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits.

PubMed

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-05-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. © 2014 Wiley Periodicals, Inc.

Molecular insights into the novel aspects of diatom biology.

PubMed

Scala, S; Bowler, C

2001-10-01

Diatoms are unicellular photosynthetic eukaryotes that are thought to contribute as much as 25% of global primary productivity. In spite of their ecological importance in the worlds oceans, very little information is available at the molecular level about the novel aspects of their biology. Recent advances, such as the development of gene transfer protocols, are now allowing the genetic dissection of diatom biology. Notable examples are advances in understanding the genetic basis for the silica-based bioinorganic pattern formation of their cell walls and for elucidating key aspects of diatom ecophysiology. The potentiation of current research will allow an evaluation of the use of diatoms to construct submicrometre-scale silicon structures for the nanotechnology industry and will reveal the molecular secrets underlying their ecological success.

No question about exciting questions in cell biology.

PubMed

Pollard, Thomas D

2013-12-01

Although we have a good grasp of many important processes in cell biology, including knowledge of many molecules involved and how they interact with each other, we still do not understand most of the dynamical features that are the essence of living systems. Fortunately, we now have the ability to dissect biological systems in enough detail to understand their dynamics, including the use of mathematical models to account for past observations and predict future experiments. This deep level of mechanistic understanding should be our goal—not simply to satisfy our scientific curiosity, but also to understand the causes of disease well enough to predict risks, make early diagnoses, and treat effectively. Many big questions remain to be answered before we reach this goal of understanding cellular dynamics.

Resuscitating the critical in the biological grotesque: blood, guts, biomachismo in science/education and human guinea pig discourse

NASA Astrophysics Data System (ADS)

Weinstein, Matthew; Broda, Matthew

2009-12-01

This article draws on Bakhtin and other cultural studies theorists to understand the role of the grotesque as a libratory moment in biology education. Four examples of texts and moments are analyzed: Sylvia Branzei's Grossology series of children's books about the grotesque, observations of a pig heart dissection, a standard high school textbook, and zines by and for human subjects. Findings confirm a powerful social leveling effect within the biological grotesque, but limits are also identified. Specifically, the grotesque itself can become a form of social capital in itself, and thus the material for establishing new hierarchies. The paper also examines the ways that teachers and texts try to limit the leveling effects of the grotesque.

Evolutionary biochemistry: revealing the historical and physical causes of protein properties

PubMed Central

Harms, Michael J.; Thornton, Joseph W.

2014-01-01

The repertoire of proteins and nucleic acids in the living world is determined by evolution; their properties are determined by the laws of physics and chemistry. Explanations of these two kinds of causality — the purviews of evolutionary biology and biochemistry, respectively — are typically pursued in isolation, but many fundamental questions fall squarely at the interface of fields. Here we articulate the paradigm of evolutionary biochemistry, which aims to dissect the physical mechanisms and evolutionary processes by which biological molecules diversified and to reveal how their physical architecture facilitates and constrains their evolution. We show how an integration of evolution with biochemistry moves us towards a more complete understanding of why biological molecules have the properties that they do. PMID:23864121

Signal transduction networks in rheumatoid arthritis

PubMed Central

Hammaker, D; Sweeney, S; Firestein, G

2003-01-01

Signal transduction pathways regulate cellular responses to stress and play a critical role in inflammation. The complexity and specificity of signalling mechanisms represent major hurdles for developing effective, safe therapeutic interventions that target specific molecules. One approach is to dissect the pathways methodically to determine their hierarchy in various cell types and diseases. This approach contributed to the identification and prioritisation of specific kinases that regulate NF-κB and the mitogen activated protein (MAP) kinase cascade as especially attractive targets. Although significant issues remain with regard to the discovery of truly selective kinase inhibitors, the risks that accompany inhibition of fundamental signal transduction mechanisms can potentially be decreased by careful dissection of the pathways and rational target selection. PMID:14532158

Bottom-Up and Top-Down Solid-State NMR Approaches for Bacterial Biofilm Matrix Composition

PubMed Central

Cegelski, Lynette

2015-01-01

The genomics and proteomics revolutions have been enormously successful in providing crucial “parts lists” for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this Perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The “sum-of-theparts” bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by E. coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in V. cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture. PMID:25797008

Bottom-up and top-down solid-state NMR approaches for bacterial biofilm matrix composition.

PubMed

Cegelski, Lynette

2015-04-01

The genomics and proteomics revolutions have been enormously successful in providing crucial "parts lists" for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The "sum-of-the-parts" bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by Escherichia coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in Vibrio cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture. Copyright © 2015 Elsevier Inc. All rights reserved.

Dissection of complex adult traits in a mouse synthetic population.

PubMed

Burke, David T; Kozloff, Kenneth M; Chen, Shu; West, Joshua L; Wilkowski, Jodi M; Goldstein, Steven A; Miller, Richard A; Galecki, Andrzej T

2012-08-01

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology.

Bottom-up and top-down solid-state NMR approaches for bacterial biofilm matrix composition

NASA Astrophysics Data System (ADS)

Cegelski, Lynette

2015-04-01

The genomics and proteomics revolutions have been enormously successful in providing crucial "parts lists" for biological systems. Yet, formidable challenges exist in generating complete descriptions of how the parts function and assemble into macromolecular complexes and whole-cell assemblies. Bacterial biofilms are complex multicellular bacterial communities protected by a slime-like extracellular matrix that confers protection to environmental stress and enhances resistance to antibiotics and host defenses. As a non-crystalline, insoluble, heterogeneous assembly, the biofilm extracellular matrix poses a challenge to compositional analysis by conventional methods. In this perspective, bottom-up and top-down solid-state NMR approaches are described for defining chemical composition in complex macrosystems. The "sum-of-the-parts" bottom-up approach was introduced to examine the amyloid-integrated biofilms formed by Escherichia coli and permitted the first determination of the composition of the intact extracellular matrix from a bacterial biofilm. An alternative top-down approach was developed to define composition in Vibrio cholerae biofilms and relied on an extensive panel of NMR measurements to tease out specific carbon pools from a single sample of the intact extracellular matrix. These two approaches are widely applicable to other heterogeneous assemblies. For bacterial biofilms, quantitative parameters of matrix composition are needed to understand how biofilms are assembled, to improve the development of biofilm inhibitors, and to dissect inhibitor modes of action. Solid-state NMR approaches will also be invaluable in obtaining parameters of matrix architecture.

Bayesian linkage and segregation analysis: factoring the problem.

PubMed

Matthysse, S

2000-01-01

Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian linkage and segregation analysis is one of integration in high-dimensional spaces. In this paper, three available techniques for Bayesian linkage and segregation analysis are discussed: Markov Chain Monte Carlo (MCMC), importance sampling, and exact calculation. The contribution of each to the overall integration will be explicitly discussed.

Endoscopic Endonasal Transclival Approach to the Ventral Brainstem: Anatomic Study of the Safe Entry Zones Combining Fiber Dissection Technique with 7 Tesla Magnetic Resonance Guided Neuronavigation.

PubMed

Weiss, Alessandro; Perrini, Paolo; De Notaris, Matteo; Soria, Guadalupe; Carlos, Alarcon; Castagna, Maura; Lutzemberger, Lodovico; Santonocito, Orazio Santo; Catapano, Giuseppe; Kassam, Amin; Galino, Alberto Prats

2018-05-10

Treatment of intrinsic lesions of the ventral brainstem is a surgical challenge that requires complex skull base antero- and posterolateral approaches. More recently, endoscopic endonasal transclival approach (EETA) has been reported in the treatment of selected ventral brainstem lesions. In this study we explored the endoscopic ventral brainstem anatomy with the aim to describe the degree of exposure of the ventral safe entry zones. In addition, we used a newly developed method combining traditional white matter dissection with high-resolution 7T magnetic resonance imaging (MRI) of the same specimen coregistered using a neuronavigation system. Eight fresh-frozen latex-injected cadaver heads underwent EETA. Additional 8 formalin-fixed brainstems were dissected using Klingler technique guided by ultra-high resolution MRI. The EETA allows a wide exposure of different safe entry zones located on the ventral brainstem: the exposure of perioculomotor zone requires pituitary transposition and can be hindered by superior cerebellar artery. The peritrigeminal zone was barely visible and its exposure required an extradural anterior petrosectomy. The anterolateral sulcus of the medulla was visible in most of specimens, although its close relationship with the corticospinal tract makes it suboptimal as an entry point for intrinsic lesions. In all cases, the use of 7T-MRI allowed the identification of tiny fiber bundles, improving the quality of the dissection. Exposure of the ventral brainstem with EETA requires mastering surgical maneuvers, including pituitary transposition and extradural petrosectomy. The correlation of fiber dissection with 7T-MRI neuronavigation significantly improves the understanding of the brainstem anatomy.

Apical polarity in three-dimensional culture systems: where to now?

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

Inman, J.L.; Bissell, Mina

2010-01-21

Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account.

INTEGRATING GENETIC AND STRUCTURAL DATA ON HUMAN PROTEIN KINOME IN NETWORK-BASED MODELING OF KINASE SENSITIVITIES AND RESISTANCE TO TARGETED AND PERSONALIZED ANTICANCER DRUGS.

PubMed

Verkhivker, Gennady M

2016-01-01

The human protein kinome presents one of the largest protein families that orchestrate functional processes in complex cellular networks, and when perturbed, can cause various cancers. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Coupled with the evolution of system biology approaches, genomic and proteomic technologies are rapidly identifying and charactering novel resistance mechanisms with the goal to inform rationale design of personalized kinase drugs. Integration of experimental and computational approaches can help to bring these data into a unified conceptual framework and develop robust models for predicting the clinical drug resistance. In the current study, we employ a battery of synergistic computational approaches that integrate genetic, evolutionary, biochemical, and structural data to characterize the effect of cancer mutations in protein kinases. We provide a detailed structural classification and analysis of genetic signatures associated with oncogenic mutations. By integrating genetic and structural data, we employ network modeling to dissect mechanisms of kinase drug sensitivities to oncogenic EGFR mutations. Using biophysical simulations and analysis of protein structure networks, we show that conformational-specific drug binding of Lapatinib may elicit resistant mutations in the EGFR kinase that are linked with the ligand-mediated changes in the residue interaction networks and global network properties of key residues that are responsible for structural stability of specific functional states. A strong network dependency on high centrality residues in the conformation-specific Lapatinib-EGFR complex may explain vulnerability of drug binding to a broad spectrum of mutations and the emergence of drug resistance. Our study offers a systems-based perspective on drug design by unravelling complex relationships between robustness of targeted kinase genes and binding specificity of targeted kinase drugs. We discuss how these approaches can exploit advances in chemical biology and network science to develop novel strategies for rationally tailored and robust personalized drug therapies.

Transcriptome inference and systems approaches to polypharmacology and drug discovery in herbal medicine.

PubMed

Li, Peng; Chen, Jianxin; Zhang, Wuxia; Fu, Bangze; Wang, Wei

2017-01-04

Herbal medicine is a concoction of numerous chemical ingredients, and it exhibits polypharmacological effects to act on multiple pharmacological targets, regulating different biological mechanisms and treating a variety of diseases. Thus, this complexity is impossible to deconvolute by the reductionist method of extracting one active ingredient acting on one biological target. To dissect the polypharmacological effects of herbal medicines and their underling pharmacological targets as well as their corresponding active ingredients. We propose a system-biology strategy that combines omics and bioinformatical methodologies for exploring the polypharmacology of herbal mixtures. The myocardial ischemia model was induced by Ameroid constriction of the left anterior descending coronary in Ba-Ma miniature pigs. RNA-seq analysis was utilized to find the differential genes induced by myocardial ischemia in pigs treated with formula QSKL. A transcriptome-based inference method was used to find the landmark drugs with similar mechanisms to QSKL. Gene-level analysis of RNA-seq data in QSKL-treated cases versus control animals yields 279 differential genes. Transcriptome-based inference methods identified 80 landmark drugs that covered nearly all drug classes. Then, based on the landmark drugs, 155 potential pharmacological targets and 57 indications were identified for QSKL. Our results demonstrate the power of a combined approach for exploring the pharmacological target and chemical space of herbal medicines. We hope that our method could enhance our understanding of the molecular mechanisms of herbal systems and further accelerate the exploration of the value of traditional herbal medicine systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Solving Problems.

ERIC Educational Resources Information Center

Hale, Norman; Lindelow, John

Chapter 12 in a volume on school leadership, this chapter cites the work of several authorities concerning problem-solving or decision-making techniques based on the belief that group problem-solving effort is preferable to individual effort. The first technique, force-field analysis, is described as a means of dissecting complex problems into…

Capturing the Peer Context: The Paradox of Progress

ERIC Educational Resources Information Center

Laursen, Brett

2010-01-01

Adolescents lead enormously complicated social lives. Many youth find it difficult to keep track of their own relationships with friends and romantic interests. For the investigator, the task is exponentially more complex because overlapping and interlocking relationships and networks must be disentangled, dissected, and diagrammed. This special…

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease.

PubMed

Marwarha, Gurdeep; Ghribi, Othman

2017-01-01

NF-κB is a ubiquitous transcription factor that was discovered three decades ago. Since its discovery, this protein complex has been implicated in numerous physiological and pathophysiological processes such as synaptic plasticity, learning and memory, inflammation, insulin resistance, and oxidative stress among other factors that are intricately involved and dysregulated in Alzheimer's disease (AD). We embarked on a methodical and an objective review of contemporary literature to integrate the indispensable physiological functions of NF-κB in neuronal phsyiology with the undesirable pathophysiological attributes of NF-κB in the etiopathogenesis of Alzheimer's disease. In our approach, we first introduced Alzheimer's disease and subsequently highlighted the multifaceted roles of NF-κB in the biological processes altered in the progression of Alzheimer's disease including synaptic transmission, synaptic plasticity, learning, and memory, neuronal survival and apoptosis, adult neurogenesis, regulation of neural processes and structural plasticity, inflammation, and Amyloid-β production and toxicity. Our comprehensive review highlights and dissects the physiological role of NF-κB from its pathological role in the brain and delineates both, its beneficial as well as deleterious, role in the etiopathogenesis of Alzheimer's disease. In light of our understanding of the duality of the role of NF-κB in the pathogenesis of Alzheimer's disease, further studies are warranted to dissect and understand the basis of the dichotomous effects of NF-κB, so that certain selective benevolent and benign attributes of NF-κB can be spared while targeting its deleterious attributes and facets that are integral in the pathogenesis of Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis

PubMed Central

Fan, Yannan; Siklenka, Keith; Arora, Simran K.; Ribeiro, Paula; Kimmins, Sarah; Xia, Jianguo

2016-01-01

MicroRNAs (miRNAs) can regulate nearly all biological processes and their dysregulation is implicated in various complex diseases and pathological conditions. Recent years have seen a growing number of functional studies of miRNAs using high-throughput experimental technologies, which have produced a large amount of high-quality data regarding miRNA target genes and their interactions with small molecules, long non-coding RNAs, epigenetic modifiers, disease associations, etc. These rich sets of information have enabled the creation of comprehensive networks linking miRNAs with various biologically important entities to shed light on their collective functions and regulatory mechanisms. Here, we introduce miRNet, an easy-to-use web-based tool that offers statistical, visual and network-based approaches to help researchers understand miRNAs functions and regulatory mechanisms. The key features of miRNet include: (i) a comprehensive knowledge base integrating high-quality miRNA-target interaction data from 11 databases; (ii) support for differential expression analysis of data from microarray, RNA-seq and quantitative PCR; (iii) implementation of a flexible interface for data filtering, refinement and customization during network creation; (iv) a powerful fully featured network visualization system coupled with enrichment analysis. miRNet offers a comprehensive tool suite to enable statistical analysis and functional interpretation of various data generated from current miRNA studies. miRNet is freely available at http://www.mirnet.ca. PMID:27105848

Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability

PubMed Central

Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

2013-01-01

In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli. PMID:24396271

A status report on RNAi therapeutics

PubMed Central

2010-01-01

Fire and Mello initiated the current explosion of interest in RNA interference (RNAi) biology with their seminal work in Caenorhabditis elegans. These observations were closely followed by the demonstration of RNAi in Drosophila melanogaster. However, the full potential of these new discoveries only became clear when Tuschl and colleagues showed that 21-22 bp RNA duplexes with 3" overhangs, termed small interfering (si)RNAs, could reliably execute RNAi in a range of mammalian cells. Soon afterwards, it became clear that many different human cell types had endogenous machinery, the RNA-induced silencing complex (RISC), which could be harnessed to silence any gene in the genome. Beyond the availability of a novel way to dissect biology, an important target validation tool was now available. More importantly, two key properties of the RNAi pathway - sequence-mediated specificity and potency - suggested that RNAi might be the most important pharmacological advance since the advent of protein therapeutics. The implications were profound. One could now envisage selecting disease-associated targets at will and expect to suppress proteins that had remained intractable to inhibition by conventional methods, such as small molecules. This review attempts to summarize the current understanding on siRNA lead discovery, the delivery of RNAi therapeutics, typical in vivo pharmacological profiles, preclinical safety evaluation and an overview of the 14 programs that have already entered clinical practice. PMID:20615220

An overview of the genetic dissection of complex traits.

PubMed

Rao, D C

2008-01-01

Thanks to the recent revolutionary genomic advances such as the International HapMap consortium, resolution of the genetic architecture of common complex traits is beginning to look hopeful. While demonstrating the feasibility of genome-wide association (GWA) studies, the pathbreaking Wellcome Trust Case Control Consortium (WTCCC) study also serves to underscore the critical importance of very large sample sizes and draws attention to potential problems, which need to be addressed as part of the study design. Even the large WTCCC study had vastly inadequate power for several of the associations reported (and confirmed) and, therefore, most of the regions harboring relevant associations may not be identified anytime soon. This chapter provides an overview of some of the key developments in the methodological approaches to genetic dissection of common complex traits. Constrained Bayesian networks are suggested as especially useful for analysis of pathway-based SNPs. Likewise, composite likelihood is suggested as a promising method for modeling complex systems. It discusses the key steps in a study design, with an emphasis on GWA studies. Potential limitations highlighted by the WTCCC GWA study are discussed, including problems associated with massive genotype imputation, analysis of pooled national samples, shared controls, and the critical role of interactions. GWA studies clearly need massive sample sizes that are only possible through genuine collaborations. After all, for common complex traits, the question is not whether we can find some pieces of the puzzle, but how large and what kind of a sample we need to (nearly) solve the genetic puzzle.

Functional Dissection: The Nemesis of Coexistence.

ERIC Educational Resources Information Center

Alloway, James A.

A former New Jersey local official discusses the complex organizational structures in universities, government, and businesses that have developed to serve the needs of citizens. Each of these specialized structures developed a rather high level of efficiency, and each set its own priorities, criteria, and cost factors. Now this functional…

The Called, Chosen, and Faithful Leader

ERIC Educational Resources Information Center

Davis, Hartwell T. Paul

2009-01-01

Leaders are made, not born. Like so many other of life's complex issues, the question of nature vs. nurture in leadership is one that is analyzed, researched, and debated by educators, philosophers, social scientist, and even leaders themselves. Leadership has been dissected as to personality, character, and behavior. Researchers have developed…

Use of a tissue sectioner to expose internal structures of biological samples for scanning electron microscopy.

PubMed

Brown, M F; Brotzman, H G; Kinden, D A

1976-09-01

A procedure yielding sections of unembedded biological samples for observation by scanning electron microscopy is described. Sections of samples, fixed and hardened in OsO4, were obtained in quantity with a tissue sectioner. Subsequent treatments to osmium-coat cut surfaces were employed prior to critical point drying. The procedure yields cleanly cut surfaces through cells and cytoplasmic organelles which are retained in their normal position. Sections of apple leaf and mouse kidney are illustrated. Sections can be readily cut in a desired plane with less structural damage than is typically encountered by other sectioning or dissection techniques.

Investigating the role of retinal Müller cells with approaches in genetics and cell biology.

PubMed

Fu, Suhua; Zhu, Meili; Ash, John D; Wang, Yunchang; Le, Yun-Zheng

2014-01-01

Müller cells are major macroglia and play many essential roles as a supporting cell in the retina. As Müller cells only constitute a small portion of retinal cells, investigating the role of Müller glia in retinal biology and diseases is particularly challenging. To overcome this problem, we first generated a Cre/lox-based conditional gene targeting system that permits the genetic manipulation and functional dissection of gene of interests in Müller cells. To investigate diabetes-induced alteration of Müller cells, we recently adopted methods to analyze Müller cells survival/death in vitro and in vivo. We also used normal and genetically altered primary cell cultures to reveal the mechanistic insights for Müller cells in biological and disease processes. In this article, we will discuss the applications and limitations of these methodologies, which may be useful for research in retinal Müller cell biology and pathophysiology.

Biological role of bacterial inclusion bodies: a model for amyloid aggregation.

PubMed

García-Fruitós, Elena; Sabate, Raimon; de Groot, Natalia S; Villaverde, Antonio; Ventura, Salvador

2011-07-01

Inclusion bodies are insoluble protein aggregates usually found in recombinant bacteria when they are forced to produce heterologous protein species. These particles are formed by polypeptides that cross-interact through sterospecific contacts and that are steadily deposited in either the cell's cytoplasm or the periplasm. An important fraction of eukaryotic proteins form inclusion bodies in bacteria, which has posed major problems in the development of the biotechnology industry. Over the last decade, the fine dissection of the quality control system in bacteria and the recognition of the amyloid-like architecture of inclusion bodies have provided dramatic insights on the dynamic biology of these aggregates. We discuss here the relevant aspects, in the interface between cell physiology and structural biology, which make inclusion bodies unique models for the study of protein aggregation, amyloid formation and prion biology in a physiologically relevant background. © 2011 The Authors Journal compilation © 2011 FEBS.

Quantification of loading in biomechanical testing: the influence of dissection sequence.

PubMed

Funabashi, Martha; El-Rich, Marwan; Prasad, Narasimha; Kawchuk, Gregory N

2015-09-18

Sequential dissection is a technique used to investigate loads experienced by articular tissues. When the joint of interest is tested in an unconstrained manner, its kinematics change with each tissue removal. To address this limitation, sufficiently rigid robots are used to constrain joint kinematics. While this approach can quantify loads experienced by each tissue, it does not assure similar results when removal order is changed. Specifically, structure loading is assumed to be independent of removal order if the structure behaves linearly (i.e. principle of superposition applies), but dependent on removal order when response is affected by material and/or geometry nonlinearities and/or viscoelasticiy (e.g. biological tissues). Therefore, this experiment was conducted to evaluate if structure loading created through robotic testing is dependent on the order in which connectors are removed. Six identical models were 3D printed. Each model was composed of 2 rigid bodies and 3 connecting structures with nonlinear time-dependent behavior. To these models, pure rotations were applied about a predefined static center of rotation using a parallel robot. A unique dissection sequence was used for each of the six models and the same movements applied robotically after each dissection. When comparing the moments experienced by each structure between different removal sequences, a statistically significant difference (p<0.05) was observed. These results suggest that even in an optimized environment, the sequence in which nonlinear viscoelastic structures are removed influence model loading. These findings support prior work suggesting that tissue loads obtained from robotic testing are specific to removal order. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative and qualitative analysis of student tutors as near-peer teachers in the gross anatomy course.

PubMed

Walser, J; Horneffer, A; Oechsner, W; Huber-Lang, M; Gerhardt-Szep, S; Boeckers, A

2017-03-01

Peer teaching is a well-established teaching method in medical education. During the 2012/13 winter term, the Institute of Anatomy and Cell Biology in Ulm, Germany, introduced a longitudinal didactics program ("Train the Tutor": TtT) to train student tutors as near-peer teachers (NPT) in the dissection course (DC). Twenty-three of 38 tutors participated in the programme. Our study describes the educational concept and the NPTs' activities in the dissection course. NPTs documented their activities on a daily basis in the form of semi-structured reports. A total of 575 reports were quantitatively and qualitatively analysed. Free-text analysis was performed using Grounded Theory followed by code quantification of all indications (n=1868). NPTs spend 61% of their time dissecting by themselves or supervising the tutee's dissection process. Organisational tasks had a larger share at the beginning of the course. Just before examinations the proportion of time spent giving feedback rose. Of all positive indications, 45% described experiences working with the tutees. In contrast, 68% of all negative indications were characterized by a self-critical reflection on their own activities. NPTs included all learning domains in their teaching, substantially functioning as teachers and role models to convey particular attitudes. TtT-Trained Tutors (NPT) clearly met the requirements of a practical course and adjusted their activities in response to the course's progress. NPTs were concerned about their tutees' attitudes and may need more professional support within the TtT program regarding this. Copyright © 2016 Elsevier GmbH. All rights reserved.

Flow-diverting Stent in the Treatment of Cervical Carotid Dissection and Pseudoaneurysm: Review of Literature and Case Report.

PubMed

Baptista-Sincos, Anna Paula Weinhardt; Simplício, Aline Bigatão; Sincos, Igor Rafael; Leaderman, Alex; Neto, Fernando Saliture; Moraes, Adjaldes; Aun, Ricardo

2018-01-01

The endovascular technique has been recommended over the past few years to extracranial carotid dissection and pseudoaneurysm with promising results, especially after medical therapy failure. Flow-diverting stents are an alternative for complex cases. These stents have proven to be effective treatment devices for intracranial aneurysms. The reference list of Pham's systematic review, published in 2011, and Seward's literature review, published in 2015, was considered, as well as all new articles with eligible features. Search was conducted on specific databases: MEDLINE and Literatura Latino-Americana e do Caribe em Ciências da Saúde. For carotid dissection and pseudoaneurysm, our review yielded 3 published articles including 12 patients. The technical success rate of flow-diverting stent was 100% with no procedural complication described. Mean clinical follow-up was 27.2 months (range 5-48), and in 5 months' angiographic follow-up, all lesions had healed. No new neurological events were reported during the clinical follow-up. Flow diverter stent use on intracranial and peripheral vascular surgery demonstrates satisfactory initial results, but it is still under investigation. There are very few cases treated till now and the initial results with flow-diverting stents to cervical carotid dissection are promising. In well-selected cases, where simple embolization or conventional stent is not appropriate, this technic may be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Neural Development Section (NDS) headed by Dr. Lino Tessarollo has an open postdoctoral fellow position. The candidate should have a background in neurobiology and basic expertise in molecular biology, cell biology, immunoistochemistry and biochemistry.  Experience in confocal analysis is desired. The NDS study the biology of neurotrophin and Trk receptors function by using both in vitro and in vivo approaches. Our group makes extensive use of engineered mouse models and cell culture models. The current research emphasis is on understanding the molecular mechanisms by which activated trk receptor function. Specifically, we are dissecting the molecular mechanism responsible for modulating Trk receptors activity, including their interaction with specific scaffold proteins and proteins leading to de-activation of Trk signaling. Moreover, we are attempting to identify new signaling pathways activated by truncated Trk receptors.

Biological atomism and cell theory.

PubMed

Nicholson, Daniel J

2010-09-01

Biological atomism postulates that all life is composed of elementary and indivisible vital units. The activity of a living organism is thus conceived as the result of the activities and interactions of its elementary constituents, each of which individually already exhibits all the attributes proper to life. This paper surveys some of the key episodes in the history of biological atomism, and situates cell theory within this tradition. The atomistic foundations of cell theory are subsequently dissected and discussed, together with the theory's conceptual development and eventual consolidation. This paper then examines the major criticisms that have been waged against cell theory, and argues that these too can be interpreted through the prism of biological atomism as attempts to relocate the true biological atom away from the cell to a level of organization above or below it. Overall, biological atomism provides a useful perspective through which to examine the history and philosophy of cell theory, and it also opens up a new way of thinking about the epistemic decomposition of living organisms that significantly departs from the physicochemical reductionism of mechanistic biology. Copyright © 2010 Elsevier Ltd. All rights reserved.

The emerging molecular biology toolbox for the study of long noncoding RNA biology.

PubMed

Fok, Ezio T; Scholefield, Janine; Fanucchi, Stephanie; Mhlanga, Musa M

2017-10-01

Long noncoding RNAs (lncRNAs) have been implicated in many biological processes. However, due to the unique nature of lncRNAs and the consequential difficulties associated with their characterization, there is a growing disparity between the rate at which lncRNAs are being discovered and the assignment of biological function to these transcripts. Here we present a molecular biology toolbox equipped to help dissect aspects of lncRNA biology and reveal functionality. We outline an approach that begins with a broad survey of genome-wide, high-throughput datasets to identify potential lncRNA candidates and then narrow the focus on specific methods that are well suited to interrogate the transcripts of interest more closely. This involves the use of imaging-based strategies to validate these candidates and observe the behaviors of these transcripts at single molecule resolution in individual cells. We also describe the use of gene editing tools and interactome capture techniques to interrogate functionality and infer mechanism, respectively. With the emergence of lncRNAs as important molecules in healthy and diseased cellular function, it remains crucial to deepen our understanding of their biology.

Reference spectra from squamous epithelium and connective tissue allow whole section proteomics analysis.

PubMed

Roesch-Ely, Mariana; Schnölzer, Martina; Nees, Matthias; Plinkert, Peter K; Bosch, Franz X

2010-01-01

We reasoned that micro-dissection of tumour cells for protein expression studies should be omitted since tumour-stroma interactions are an important part of the biology of solid tumours. To study such interactions in head and neck squamous cell carcinoma (HNSCC) development, we generated reference protein spectra for normal squamous epithelium and connective tissue by SELDI-TOF-MS. Calgranulins A and B, Annexin1 and Histone H4 were found to be strongly enriched in the epithelium. The alpha-defensins 1-3 and the haemoglobin subunits were identified in the connective tissue. Tumour-distant epithelia, representing early pre-malignant lesions, showed up-regulated expression of the stromal alpha-defensins, whereas the epithelial Annexin 1 was down-regulated. Thus, tumour microenvironment interactions occur very early in the carcinogenic process. These data demonstrate that omitting micro-dissection is actually beneficial for studying changes in protein expression during development and progression of solid tumours.

[The first experience with the concurrent effect of YAG-neodymium and YAG-erbium laser on experimental animal tissues and the possibility of its use in surgery].

PubMed

Roshal', L M; Gorbatova, N E; Livshits, Iu L; Parkhomenko, Iu G; Osiko, V V; Danileĭko, Iu K; Sidorin, A V; Tylaĭkova, T B; Ivanov, A D

1991-08-01

To guarantee the necessary rate of cutting live tissues with adequate hemostasis along the line of the incision, the authors studied isolated and joint effect of radiations of AIG-neodymium and AIG-erbium lasers on the tissues of laboratory animals. The possibility of accomplishing intraoperative hemostasis on the parenchymal organs was studied in experiments with AIG-neodymium laser. A good dissection effect in cutting various tissues was produced in the second series of experiments with AIG-erbium laser. The simultaneous action of AIG-neodymium and AIG-erbium beams converged at one point on the surface of the biological object was studied in the third series of experiments. It was found that the effect ensures a good dissection of tissues with sufficient hemostasis. The results of dynamic morphological studies are shown. The possibility of using the device in surgery is discussed.

Application of TALE-Based Approach for Dissecting Functional MicroRNA-302/367 in Cellular Reprogramming.

PubMed

Zhang, Zhonghui; Wu, Wen-Shu

2018-01-01

MicroRNAs are small 18-24 nt single-stranded noncoding RNA molecules involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs have several limitations. Here, we describe a new approach for dissecting miR-302/367 functions by transcription activator-like effectors (TALEs), which are natural effector proteins secreted by Xanthomonas and Ralstonia bacteria. Knockdown of the miR-302/367 cluster uses the Kruppel-associated box repressor domain fused with specific TALEs designed to bind the miR-302/367 cluster promoter. Knockout of the miR-302/367 cluster uses two pairs of TALE nucleases (TALENs) to delete the miR-302/367 cluster in human primary cells. Together, both TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA cluster in human primary cells.

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4-based dissection of protocerebral bridge neurons and circuits

PubMed Central

Wolff, Tanya; Iyer, Nirmala A; Rubin, Gerald M

2015-01-01

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip-out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. J. Comp. Neurol. 523:997–1037, 2015. © 2014 Wiley Periodicals, Inc. PMID:25380328

The enduring importance of animal modelsin understanding periodontal disease

PubMed Central

Hajishengallis, George; Lamont, Richard J; Graves, Dana T

2015-01-01

Whereas no single animal model can reproduce the complexity of periodontitis, different aspects of the disease can be addressed by distinct models. Despite their limitations, animal models are essential for testing the biological significance of in vitro findings and for establishing cause-and-effect relationships relevant to clinical observations, which are typically correlative. We provide evidence that animal-based studies have generated a durable framework for dissecting the mechanistic basis of periodontitis. These studies have solidified the etiologic role of bacteria in initiating the inflammatory response that leads to periodontal bone loss and have identified key mediators (IL-1, TNF, prostaglandins, complement, RANKL) that induce inflammatory breakdown. Moreover, animal studies suggest that dysbiosis, rather than individual bacterial species, are important in initiating periodontal bone loss and have introduced the concept that organisms previously considered commensals can play important roles as accessory pathogens or pathobionts. These studies have also provided insight as to how systemic conditions, such as diabetes or leukocyte adhesion deficiency, contribute to tissue destruction. In addition, animal studies have identified and been useful in testing therapeutic targets. PMID:25574929

Global Quantitative Modeling of Chromatin Factor Interactions

PubMed Central

Zhou, Jian; Troyanskaya, Olga G.

2014-01-01

Chromatin is the driver of gene regulation, yet understanding the molecular interactions underlying chromatin factor combinatorial patterns (or the “chromatin codes”) remains a fundamental challenge in chromatin biology. Here we developed a global modeling framework that leverages chromatin profiling data to produce a systems-level view of the macromolecular complex of chromatin. Our model ultilizes maximum entropy modeling with regularization-based structure learning to statistically dissect dependencies between chromatin factors and produce an accurate probability distribution of chromatin code. Our unsupervised quantitative model, trained on genome-wide chromatin profiles of 73 histone marks and chromatin proteins from modENCODE, enabled making various data-driven inferences about chromatin profiles and interactions. We provided a highly accurate predictor of chromatin factor pairwise interactions validated by known experimental evidence, and for the first time enabled higher-order interaction prediction. Our predictions can thus help guide future experimental studies. The model can also serve as an inference engine for predicting unknown chromatin profiles — we demonstrated that with this approach we can leverage data from well-characterized cell types to help understand less-studied cell type or conditions. PMID:24675896

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines

PubMed Central

Gasparini, R.; Panatto, D.; Bragazzi, N. L.; Lai, P. L.; Bechini, A.; Levi, M.; Durando, P.; Amicizia, D.

2015-01-01

In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics). Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains. PMID:26351643

Systematic Overview of Solid Particles and Their Host Responses

PubMed Central

Shu, Fei; Shi, Yan

2018-01-01

Crystalline/particulate substances trigger a plethora of signaling events in host cells. The most prominent consequence is the inflammatory reactions that underlie crystal arthropathies, such as gout and pseudogout. However, their impact on our health was underestimated. Recent work on the role of cholesterol crystal in the development of atherosclerosis and the harm of environmental particulates has set up new frontiers in our defense against their detrimental effects. On the other hand, in the last 100 years, crystalline/particulate substances have been used with increasing frequencies in our daily lives as a part of new industrial manufacturing and engineering. Importantly, they have become a tool in modern medicine, used as vaccine adjuvants and drug delivery vehicles. Their biological effects are also being dissected in great detail, particularly with regard to their inflammatory signaling pathways. Solid structure interaction with host cells is far from being uniform, with outcomes dependent on cell types and chemical/physical properties of the particles involved. In this review, we offer a systematic and broad outlook of this landscape and a sage analysis of the complex nature of this topic. PMID:29892295

Single-Molecule Real-Time 3D Imaging of the Transcription Cycle by Modulation Interferometry.

PubMed

Wang, Guanshi; Hauver, Jesse; Thomas, Zachary; Darst, Seth A; Pertsinidis, Alexandros

2016-12-15

Many essential cellular processes, such as gene control, employ elaborate mechanisms involving the coordination of large, multi-component molecular assemblies. Few structural biology tools presently have the combined spatial-temporal resolution and molecular specificity required to capture the movement, conformational changes, and subunit association-dissociation kinetics, three fundamental elements of how such intricate molecular machines work. Here, we report a 3D single-molecule super-resolution imaging study using modulation interferometry and phase-sensitive detection that achieves <2 nm axial localization precision, well below the few-nanometer-sized individual protein components. To illustrate the capability of this technique in probing the dynamics of complex macromolecular machines, we visualize the movement of individual multi-subunit E. coli RNA polymerases through the complete transcription cycle, dissect the kinetics of the initiation-elongation transition, and determine the fate of σ 70 initiation factors during promoter escape. Modulation interferometry sets the stage for single-molecule studies of several hitherto difficult-to-investigate multi-molecular transactions that underlie genome regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory.

PubMed

Ikemoto, Satoshi

2010-11-01

Reductionist attempts to dissect complex mechanisms into simpler elements are necessary, but not sufficient for understanding how biological properties like reward emerge out of neuronal activity. Recent studies on intracranial self-administration of neurochemicals (drugs) found that rats learn to self-administer various drugs into the mesolimbic dopamine structures-the posterior ventral tegmental area, medial shell nucleus accumbens and medial olfactory tubercle. In addition, studies found roles of non-dopaminergic mechanisms of the supramammillary, rostromedial tegmental and midbrain raphe nuclei in reward. To explain intracranial self-administration and related effects of various drug manipulations, I outlined a neurobiological theory claiming that there is an intrinsic central process that coordinates various selective functions (including perceptual, visceral, and reinforcement processes) into a global function of approach. Further, this coordinating process for approach arises from interactions between brain structures including those structures mentioned above and their closely linked regions: the medial prefrontal cortex, septal area, ventral pallidum, bed nucleus of stria terminalis, preoptic area, lateral hypothalamic areas, lateral habenula, periaqueductal gray, laterodorsal tegmental nucleus and parabrachical area. Published by Elsevier Ltd.

Transoral robotic surgery for neurogenic tumors of the prestyloid parapharyngeal space.

PubMed

Lee, Hyoung Shin; Kim, Jinna; Lee, Hyun Jin; Koh, Yoon Woo; Choi, Eun Chang

2012-08-01

The parapharyngeal space is a difficult area for a surgical approach due to anatomical complexity. We performed a minimally invasive and precise surgical technique to remove neurogenic tumors of the prestyloid parapharyngeal space using transoral robotic instrumentation. The mass was successfully removed in the two cases with three-dimensional visualization providing an excellent view of the resection margin and the dissection plane preserving the vital structures. An adequate resection margin was acquired, and no violation of the tumor capsule occurred. No significant complications were noted. Transoral robotic surgery was feasible for neurogenic tumors of the prestyloid parapharyngeal space, providing a sufficient resection margin and delicate dissection through excellent surgical views and instrumentation. Copyright © 2012. Published by Elsevier Ireland Ltd.

Modelling of aortic aneurysm and aortic dissection through 3D printing.

PubMed

Ho, Daniel; Squelch, Andrew; Sun, Zhonghua

2017-03-01

The aim of this study was to assess if the complex anatomy of aortic aneurysm and aortic dissection can be accurately reproduced from a contrast-enhanced computed tomography (CT) scan into a three-dimensional (3D) printed model. Contrast-enhanced cardiac CT scans from two patients were post-processed and produced as 3D printed thoracic aorta models of aortic aneurysm and aortic dissection. The transverse diameter was measured at five anatomical landmarks for both models, compared across three stages: the original contrast-enhanced CT images, the stereolithography (STL) format computerised model prepared for 3D printing and the contrast-enhanced CT of the 3D printed model. For the model with aortic dissection, measurements of the true and false lumen were taken and compared at two points on the descending aorta. Three-dimensional printed models were generated with strong and flexible plastic material with successful replication of anatomical details of aortic structures and pathologies. The mean difference in transverse vessel diameter between the contrast-enhanced CT images before and after 3D printing was 1.0 and 1.2 mm, for the first and second models respectively (standard deviation: 1.0 mm and 0.9 mm). Additionally, for the second model, the mean luminal diameter difference between the 3D printed model and CT images was 0.5 mm. Encouraging results were achieved with regards to reproducing 3D models depicting aortic aneurysm and aortic dissection. Variances in vessel diameter measurement outside a standard deviation of 1 mm tolerance indicate further work is required into the assessment and accuracy of 3D model reproduction. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Dissection of a single rat muscle-tendon complex changes joint moments exerted by neighboring muscles: implications for invasive surgical interventions.

PubMed

Maas, Huub; Baan, Guus C; Huijing, Peter A

2013-01-01

The aim of this paper is to investigate mechanical functioning of a single skeletal muscle, active within a group of (previously) synergistic muscles. For this purpose, we assessed wrist angle-active moment characteristics exerted by a group of wrist flexion muscles in the rat for three conditions: (i) after resection of the upper arm skin; (ii) after subsequent distal tenotomy of flexor carpi ulnaris muscle (FCU); and (iii) after subsequent freeing of FCU distal tendon and muscle belly from surrounding tissues (MT dissection). Measurements were performed for a control group and for an experimental group after recovery (5 weeks) from tendon transfer of FCU to extensor carpi radialis (ECR) insertion. To assess if FCU tenotomy and MT dissection affects FCU contributions to wrist moments exclusively or also those of neighboring wrist flexion muscles, these data were compared to wrist angle-moment characteristics of selectively activated FCU. FCU tenotomy and MT dissection decreased wrist moments of the control group at all wrist angles tested, including also angles for which no or minimal wrist moments were measured when activating FCU exclusively. For the tendon transfer group, wrist flexion moment increased after FCU tenotomy, but to a greater extent than can be expected based on wrist extension moments exerted by selectively excited transferred FCU. We conclude that dissection of a single muscle in any surgical treatment does not only affect mechanical characteristics of the target muscle, but also those of other muscles within the same compartment. Our results demonstrate also that even after agonistic-to-antagonistic tendon transfer, mechanical interactions with previously synergistic muscles do remain present.

When galectins recognize glycans: from biochemistry to physiology and back again.

PubMed

Di Lella, Santiago; Sundblad, Victoria; Cerliani, Juan P; Guardia, Carlos M; Estrin, Dario A; Vasta, Gerardo R; Rabinovich, Gabriel A

2011-09-20

In the past decade, increasing efforts have been devoted to the study of galectins, a family of evolutionarily conserved glycan-binding proteins with multifunctional properties. Galectins function, either intracellularly or extracellularly, as key biological mediators capable of monitoring changes occurring on the cell surface during fundamental biological processes such as cellular communication, inflammation, development, and differentiation. Their highly conserved structures, exquisite carbohydrate specificity, and ability to modulate a broad spectrum of biological processes have captivated a wide range of scientists from a wide spectrum of disciplines, including biochemistry, biophysics, cell biology, and physiology. However, in spite of enormous efforts to dissect the functions and properties of these glycan-binding proteins, limited information about how structural and biochemical aspects of these proteins can influence biological functions is available. In this review, we aim to integrate structural, biochemical, and functional aspects of this bewildering and ancient family of glycan-binding proteins and discuss their implications in physiologic and pathologic settings. © 2011 American Chemical Society

Dissecting Redox Biology Using Fluorescent Protein Sensors.

PubMed

Schwarzländer, Markus; Dick, Tobias P; Meyer, Andreas J; Morgan, Bruce

2016-05-01

Fluorescent protein sensors have revitalized the field of redox biology by revolutionizing the study of redox processes in living cells and organisms. Within one decade, a set of fundamental new insights has been gained, driven by the rapid technical development of in vivo redox sensing. Redox-sensitive yellow and green fluorescent protein variants (rxYFP and roGFPs) have been the central players. Although widely used as an established standard tool, important questions remain surrounding their meaningful use in vivo. We review the growing range of thiol redox sensor variants and their application in different cells, tissues, and organisms. We highlight five key findings where in vivo sensing has been instrumental in changing our understanding of redox biology, critically assess the interpretation of in vivo redox data, and discuss technical and biological limitations of current redox sensors and sensing approaches. We explore how novel sensor variants may further add to the current momentum toward a novel mechanistic and integrated understanding of redox biology in vivo. Antioxid. Redox Signal. 24, 680-712.

A 3D anatomical atlas of appendage musculature in the chelicerate arthropod Limulus polyphemus

PubMed Central

Wroe, Stephen; Paterson, John R.

2018-01-01

Limulus polyphemus, an archetypal chelicerate taxon, has interested both biological and paleontological researchers due to its unique suite of anatomical features and as a useful modern analogue for fossil arthropod groups. To assist the study and documentation of this iconic taxon, we present a 3D atlas on the appendage musculature, with specific focus on the muscles of the cephalothoracic appendages. As L. polyphemus appendage musculature has been the focus of extensive study, depicting the muscles in 3D will facilitate a more complete understanding thereof for future researchers. A large museum specimen was CT scanned to illustrate the major exoskeletal features of L. polyphemus. Micro-CT scans of iodine-stained appendages from fresh, non-museum specimens were digitally dissected to interactively depict appendage sections and muscles. This study has revealed the presence of two new muscles: one within the pushing leg, located dorsally relative to all other patella muscles, and the other within the male pedipalp, located in the modified tibiotarsus. This atlas increases accessibility to important internal and external morphological features of L. polyphemus and reduces the need for destructive fresh tissue dissection of specimens. Scanning, digitally dissecting, and documenting taxa in 3D is a pivotal step towards creating permanent digital records of life on Earth. PMID:29444161

Dissecting the genetics of complex traits using summary association statistics.

PubMed

Pasaniuc, Bogdan; Price, Alkes L

2017-02-01

During the past decade, genome-wide association studies (GWAS) have been used to successfully identify tens of thousands of genetic variants associated with complex traits and diseases. These studies have produced extensive repositories of genetic variation and trait measurements across large numbers of individuals, providing tremendous opportunities for further analyses. However, privacy concerns and other logistical considerations often limit access to individual-level genetic data, motivating the development of methods that analyse summary association statistics. Here, we review recent progress on statistical methods that leverage summary association data to gain insights into the genetic basis of complex traits and diseases.

Dissecting the genetics of complex traits using summary association statistics

PubMed Central

Pasaniuc, Bogdan; Price, Alkes L.

2017-01-01

During the past decade, genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants associated with complex traits and diseases. These studies have produced extensive repositories of genetic variation and trait measurements across large numbers of individuals, providing tremendous opportunities for further analyses. However, privacy concerns and other logistical considerations often limit access to individual-level genetic data, motivating the development of methods that analyze summary association statistics. Here we review recent progress on statistical methods that leverage summary association data to gain insights into the genetic basis of complex traits and diseases. PMID:27840428

Anaerobic Formate and Hydrogen Metabolism.

PubMed

Pinske, Constanze; Sawers, R Gary

2016-10-01

Numerous recent developments in the biochemistry, molecular biology, and physiology of formate and H2 metabolism and of the [NiFe]-hydrogenase (Hyd) cofactor biosynthetic machinery are highlighted. Formate export and import by the aquaporin-like pentameric formate channel FocA is governed by interaction with pyruvate formate-lyase, the enzyme that generates formate. Formate is disproportionated by the reversible formate hydrogenlyase (FHL) complex, which has been isolated, allowing biochemical dissection of evolutionary parallels with complex I of the respiratory chain. A recently identified sulfido-ligand attached to Mo in the active site of formate dehydrogenases led to the proposal of a modified catalytic mechanism. Structural analysis of the homologous, H2-oxidizing Hyd-1 and Hyd-5 identified a novel proximal [4Fe-3S] cluster in the small subunit involved in conferring oxygen tolerance to the enzymes. Synthesis of Salmonella Typhimurium Hyd-5 occurs aerobically, which is novel for an enterobacterial Hyd. The O2-sensitive Hyd-2 enzyme has been shown to be reversible: it presumably acts as a conformational proton pump in the H2-oxidizing mode and is capable of coupling reverse electron transport to drive H2 release. The structural characterization of all the Hyp maturation proteins has given new impulse to studies on the biosynthesis of the Fe(CN)2CO moiety of the [NiFe] cofactor. It is synthesized on a Hyp-scaffold complex, mainly comprising HypC and HypD, before insertion into the apo-large subunit. Finally, clear evidence now exists indicating that Escherichia coli can mature Hyd enzymes differentially, depending on metal ion availability and the prevailing metabolic state. Notably, Hyd-3 of the FHL complex takes precedence over the H2-oxidizing enzymes.

Genomic anatomy of the Tyrp1 (brown) deletion complex

PubMed Central

Smyth, Ian M.; Wilming, Laurens; Lee, Angela W.; Taylor, Martin S.; Gautier, Phillipe; Barlow, Karen; Wallis, Justine; Martin, Sancha; Glithero, Rebecca; Phillimore, Ben; Pelan, Sarah; Andrew, Rob; Holt, Karen; Taylor, Ruth; McLaren, Stuart; Burton, John; Bailey, Jonathon; Sims, Sarah; Squares, Jan; Plumb, Bob; Joy, Ann; Gibson, Richard; Gilbert, James; Hart, Elizabeth; Laird, Gavin; Loveland, Jane; Mudge, Jonathan; Steward, Charlie; Swarbreck, David; Harrow, Jennifer; North, Philip; Leaves, Nicholas; Greystrong, John; Coppola, Maria; Manjunath, Shilpa; Campbell, Mark; Smith, Mark; Strachan, Gregory; Tofts, Calli; Boal, Esther; Cobley, Victoria; Hunter, Giselle; Kimberley, Christopher; Thomas, Daniel; Cave-Berry, Lee; Weston, Paul; Botcherby, Marc R. M.; White, Sharon; Edgar, Ruth; Cross, Sally H.; Irvani, Marjan; Hummerich, Holger; Simpson, Eleanor H.; Johnson, Dabney; Hunsicker, Patricia R.; Little, Peter F. R.; Hubbard, Tim; Campbell, R. Duncan; Rogers, Jane; Jackson, Ian J.

2006-01-01

Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (Bw). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis. PMID:16505357

Bamberg Crater

NASA Image and Video Library

2018-04-26

Today's VIS image shows the western rim of Bamberg Crater. The complex nature of the rim is one indication of the relative youth of this crater in relation to it's surrounding. Many gullies dissect this rim. Orbit Number: 71254 Latitude: 39.6224 Longitude: 356.451 Instrument: VIS Captured: 2018-01-06 05:00 https://photojournal.jpl.nasa.gov/catalog/PIA22378

Virtual Cerebral Ventricular System: An MR-Based Three-Dimensional Computer Model

ERIC Educational Resources Information Center

Adams, Christina M.; Wilson, Timothy D.

2011-01-01

The inherent spatial complexity of the human cerebral ventricular system, coupled with its deep position within the brain, poses a problem for conceptualizing its anatomy. Cadaveric dissection, while considered the gold standard of anatomical learning, may be inadequate for learning the anatomy of the cerebral ventricular system; even with…

Association genetics in Pinus taeda L. I. wood property traits

Treesearch

Santiago C. Gonzalez-Martinez; Nicholas C. Wheeler; Elhan Ersoz; C. Dana Nelson; David B. Neale

2007-01-01

Genetic association is a powerful method for dissecting complex adaptive traits due to (i) fine-scale mapping resulting from historical recombination, (ii) wide coverage of phenotypic and genotypic variation within a single experiment, and (iii) the simultaneous discovery of loci and alleles. In this article, genetic association among single nucleotide polymorphisms (...

Complexity and specificity of the maize (Zea mays L.) root hair transcriptome.

PubMed

Hey, Stefan; Baldauf, Jutta; Opitz, Nina; Lithio, Andrew; Pasha, Asher; Provart, Nicholas; Nettleton, Dan; Hochholdinger, Frank

2017-04-01

Root hairs are tubular extensions of epidermis cells. Transcriptome profiling demonstrated that the single cell-type root hair transcriptome was less complex than the transcriptome of multiple cell-type primary roots without root hairs. In total, 831 genes were exclusively and 5585 genes were preferentially expressed in root hairs [false discovery rate (FDR) ≤1%]. Among those, the most significantly enriched Gene Ontology (GO) functional terms were related to energy metabolism, highlighting the high energy demand for the development and function of root hairs. Subsequently, the maize homologs for 138 Arabidopsis genes known to be involved in root hair development were identified and their phylogenetic relationship and expression in root hairs were determined. This study indicated that the genetic regulation of root hair development in Arabidopsis and maize is controlled by common genes, but also shows differences which need to be dissected in future genetic experiments. Finally, a maize root view of the eFP browser was implemented including the root hair transcriptome of the present study and several previously published maize root transcriptome data sets. The eFP browser provides color-coded expression levels for these root types and tissues for any gene of interest, thus providing a novel resource to study gene expression and function in maize roots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

MAGIA2: from miRNA and genes expression data integrative analysis to microRNA–transcription factor mixed regulatory circuits (2012 update)

PubMed Central

Bisognin, Andrea; Sales, Gabriele; Coppe, Alessandro; Bortoluzzi, Stefania; Romualdi, Chiara

2012-01-01

MAGIA2 (http://gencomp.bio.unipd.it/magia2) is an update, extension and evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in silico target prediction, microRNA (miRNA) and gene expression data for the reconstruction of post-transcriptional regulatory networks. miRNAs are fundamental post-transcriptional regulators of several key biological and pathological processes. As miRNAs act prevalently through target degradation, their expression profiles are expected to be inversely correlated to those of the target genes. Low specificity of target prediction algorithms makes integration approaches an interesting solution for target prediction refinement. MAGIA2 performs this integrative approach supporting different association measures, multiple organisms and almost all target predictions algorithms. Nevertheless, miRNAs activity should be viewed as part of a more complex scenario where regulatory elements and their interactors generate a highly connected network and where gene expression profiles are the result of different levels of regulation. The updated MAGIA2 tries to dissect this complexity by reconstructing mixed regulatory circuits involving either miRNA or transcription factor (TF) as regulators. Two types of circuits are identified: (i) a TF that regulates both a miRNA and its target and (ii) a miRNA that regulates both a TF and its target. PMID:22618880

Lipidomic profiling of bioactive lipids by mass spectrometry during microbial infections.

PubMed

Tam, Vincent C

2013-10-31

Bioactive lipid mediators play crucial roles in promoting the induction and resolution of inflammation. Eicosanoids and other related unsaturated fatty acids have long been known to induce inflammation. These signaling molecules can modulate the circulatory system and stimulate immune cell infiltration into the site of infection. Recently, DHA- and EPA-derived metabolites have been discovered to promote the resolution of inflammation, an active process. Not only do these molecules stop the further infiltration of immune cells, they prompt non-phlogistic phagocytosis of apoptotic neutrophils, stimulating the tissue to return to homeostasis. After the rapid release of lipid precursors from the plasma membrane upon stimulation, families of enzymes in a complex network metabolize them to produce a large array of lipid metabolites. With current advances in mass spectrometry, the entire lipidome can be accurately quantified to assess the immune response upon microbial infection. In this review, we discuss the various lipid metabolism pathways in the context of the immune response to microbial pathogens, as well as their complex network interactions. With the advancement of mass spectrometry, these approaches have also been used to characterize the lipid mediator response of macrophages and neutrophils upon immune stimulation in vitro. Lastly, we describe the recent efforts to apply systems biology approaches to dissect the role of lipid mediators during bacterial and viral infections in vivo. Copyright © 2013 Elsevier Ltd. All rights reserved.

What rheumatologists need to know about CRISPR/Cas9.

PubMed

Gibson, Gary J; Yang, Maozhou

2017-04-01

CRISPR/Cas9 genome editing technology has taken the research world by storm since its use in eukaryotes was first proposed in 2012. Publications describing advances in technology and new applications have continued at an unrelenting pace since that time. In this Review, we discuss the application of CRISPR/Cas9 for creating gene mutations - the application that initiated the current avalanche of interest - and new developments that have largely answered initial concerns about its specificity and ability to introduce new gene sequences. We discuss the new, diverse and rapidly growing adaptations of the CRISPR/Cas9 technique that enable activation, repression, multiplexing and gene screening. These developments have enabled researchers to create sophisticated tools for dissecting the function and inter-relatedness of genes, as well as noncoding regions of the genome, and to identify gene networks and noncoding regions that promote disease or confer disease susceptibility. These approaches are beginning to be used to interrogate complex and multilayered biological systems and to produce complex animal models of disease. CRISPR/Cas9 technology has enabled the application of new therapeutic approaches to treating disease in animal models, some of which are beginning to be seen in the first human clinical trials. We discuss the direct application of these techniques to rheumatic diseases, which are currently limited but are sure to increase rapidly in the near future.

Estimation and Partitioning of Heritability in Human Populations using Whole Genome Analysis Methods

PubMed Central

Vinkhuyzen, Anna AE; Wray, Naomi R; Yang, Jian; Goddard, Michael E; Visscher, Peter M

2014-01-01

Understanding genetic variation of complex traits in human populations has moved from the quantification of the resemblance between close relatives to the dissection of genetic variation into the contributions of individual genomic loci. But major questions remain unanswered: how much phenotypic variation is genetic, how much of the genetic variation is additive and what is the joint distribution of effect size and allele frequency at causal variants? We review and compare three whole-genome analysis methods that use mixed linear models (MLM) to estimate genetic variation, using the relationship between close or distant relatives based on pedigree or SNPs. We discuss theory, estimation procedures, bias and precision of each method and review recent advances in the dissection of additive genetic variation of complex traits in human populations that are based upon the application of MLM. Using genome wide data, SNPs account for far more of the genetic variation than the highly significant SNPs associated with a trait, but they do not account for all of the genetic variance estimated by pedigree based methods. We explain possible reasons for this ‘missing’ heritability. PMID:23988118

A chromatin activity based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing

PubMed Central

Liu, Cui; Yu, Yanbao; Liu, Feng; Wei, Xin; Wrobel, John A.; Gunawardena, Harsha P.; Zhou, Li; Jin, Jian; Chen, Xian

2015-01-01

Immune cells develop endotoxin tolerance (ET) after prolonged stimulation. ET increases the level of a repression mark H3K9me2 in the transcriptional-silent chromatin specifically associated with pro-inflammatory genes. However, it is not clear what proteins are functionally involved in this process. Here we show that a novel chromatin activity based chemoproteomic (ChaC) approach can dissect the functional chromatin protein complexes that regulate ET-associated inflammation. Using UNC0638 that binds the enzymatically active H3K9-specific methyltransferase G9a/GLP, ChaC reveals that G9a is constitutively active at a G9a-dependent mega-dalton repressome in primary endotoxin-tolerant macrophages. G9a/GLP broadly impacts the ET-specific reprogramming of the histone code landscape, chromatin remodeling, and the activities of select transcription factors. We discover that the G9a-dependent epigenetic environment promotes the transcriptional repression activity of c-Myc for gene-specific co-regulation of chronic inflammation. ChaC may be also applicable to dissect other functional protein complexes in the context of phenotypic chromatin architectures. PMID:25502336

Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates

PubMed Central

Skerker, Jeffrey M; Leon, Dacia; Price, Morgan N; Mar, Jordan S; Tarjan, Daniel R; Wetmore, Kelly M; Deutschbauer, Adam M; Baumohl, Jason K; Bauer, Stefan; Ibáñez, Ana B; Mitchell, Valerie D; Wu, Cindy H; Hu, Ping; Hazen, Terry; Arkin, Adam P

2013-01-01

The efficient production of biofuels from cellulosic feedstocks will require the efficient fermentation of the sugars in hydrolyzed plant material. Unfortunately, plant hydrolysates also contain many compounds that inhibit microbial growth and fermentation. We used DNA-barcoded mutant libraries to identify genes that are important for hydrolysate tolerance in both Zymomonas mobilis (44 genes) and Saccharomyces cerevisiae (99 genes). Overexpression of a Z. mobilis tolerance gene of unknown function (ZMO1875) improved its specific ethanol productivity 2.4-fold in the presence of miscanthus hydrolysate. However, a mixture of 37 hydrolysate-derived inhibitors was not sufficient to explain the fitness profile of plant hydrolysate. To deconstruct the fitness profile of hydrolysate, we profiled the 37 inhibitors against a library of Z. mobilis mutants and we modeled fitness in hydrolysate as a mixture of fitness in its components. By examining outliers in this model, we identified methylglyoxal as a previously unknown component of hydrolysate. Our work provides a general strategy to dissect how microbes respond to a complex chemical stress and should enable further engineering of hydrolysate tolerance. PMID:23774757

[Research status and prospects of DNA test on difficult specimens].

PubMed

Dang, Hua-Wei; Mao, Jiong; Wang, Hui; Huang, Jiang-Ping; Bai, Xiao-Gang

2012-02-01

This paper reviews the advances of DNA detection on three types of difficult biological specimens including degraded samples, trace evidences and mixed samples. The source of different samples, processing methods and announcements were analyzed. New methods such as mitochondrial test system, changing the original experimental conditions, low-volume PCR amplification and new technologies such as whole genome amplification techniques, laser capture micro-dissection, and mini-STR technology in recent years are introduced.

Dissection of Signaling Events Downstream of the c-Mpl Receptor in Murine Hematopoietic Stem Cells Via Motif-Engineered Chimeric Receptors.

PubMed

Saka, Koichiro; Lai, Chen-Yi; Nojima, Masanori; Kawahara, Masahiro; Otsu, Makoto; Nakauchi, Hiromitsu; Nagamune, Teruyuki

2018-02-01

Hematopoietic stem cells (HSCs) are a valuable resource in transplantation medicine. Cytokines are often used to culture HSCs aiming at better clinical outcomes through enhancement of HSC reconstitution capability. Roles for each signal molecule downstream of receptors in HSCs, however, remain puzzling due to complexity of the cytokine-signaling network. Engineered receptors that are non-responsive to endogenous cytokines represent an attractive tool for dissection of signaling events. We here tested a previously developed chimeric receptor (CR) system in primary murine HSCs, target cells that are indispensable for analysis of stem cell activity. Each CR contains tyrosine motifs that enable selective activation of signal molecules located downstream of the c-Mpl receptor upon stimulation by an artificial ligand. Signaling through a control CR with a wild-type c-Mpl cytoplasmic tail sufficed to enhance HSC proliferation and colony formation in cooperation with stem cell factor (SCF). Among a series of CRs, only one compatible with selective Stat5 activation showed similar positive effects. The HSCs maintained ex vivo in these environments retained long-term reconstitution ability following transplantation. This ability was also demonstrated in secondary recipients, indicating effective transmission of stem cell-supportive signals into HSCs via these artificial CRs during culture. Selective activation of Stat5 through CR ex vivo favored preservation of lymphoid potential in long-term reconstituting HSCs, but not of myeloid potential, exemplifying possible dissection of signals downstream of c-Mpl. These CR systems therefore offer a useful tool to scrutinize complex signaling pathways in HSCs.

Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population.

PubMed

Karaca, Sefayet; Erge, Sema; Cesuroglu, Tomris; Polimanti, Renato

2016-06-01

Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Chaperone-subunit Usher Domain Interactions in the Mechanism of Bacterial Pilus Biogenesis Revealed by ESI-MS*

PubMed Central

Morrissey, Bethny; Leney, Aneika C.; Toste Rêgo, Ana; Phan, Gilles; Allen, William J.; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E.; Radford, Sheena E.

2012-01-01

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species. PMID:22371487

The role of chaperone-subunit usher domain interactions in the mechanism of bacterial pilus biogenesis revealed by ESI-MS.

PubMed

Morrissey, Bethny; Leney, Aneika C; Toste Rêgo, Ana; Phan, Gilles; Allen, William J; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E; Radford, Sheena E

2012-07-01

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species.

Time-course, negative-stain electron microscopy-based analysis for investigating protein-protein interactions at the single-molecule level.

PubMed

Nogal, Bartek; Bowman, Charles A; Ward, Andrew B

2017-11-24

Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein-protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate time scale. Using the HIV-1 envelope glycoprotein (Env) and its interaction with receptor CD4-binding site neutralizing antibodies as a model system, we both corroborate ensemble kinetics-derived parameters and demonstrate how time-course EM can further dissect stoichiometric states of complexes that are not readily observable with other methods. Visualization of the kinetics and stoichiometry of Env-antibody complexes demonstrated the applicability of our approach to qualitatively and semi-quantitatively differentiate two highly similar neutralizing antibodies. Furthermore, implementation of machine-learning techniques for sorting class averages of these complexes into discrete subclasses of particles helped reduce human bias. Our data provide proof of concept that single-particle EM can be used to generate a "visual" kinetic profile that should be amenable to studying many other protein-protein interactions, is relatively simple and complementary to well-established biophysical approaches. Moreover, our method provides critical insights into broadly neutralizing antibody recognition of Env, which may inform vaccine immunogen design and immunotherapeutic development. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Endocytosis and Signaling during Development

PubMed Central

Bökel, Christian

2014-01-01

The development of multicellular organisms relies on an intricate choreography of intercellular communication events that pattern the embryo and coordinate the formation of tissues and organs. It is therefore not surprising that developmental biology, especially using genetic model organisms, has contributed significantly to the discovery and functional dissection of the associated signal-transduction cascades. At the same time, biophysical, biochemical, and cell biological approaches have provided us with insights into the underlying cell biological machinery. Here we focus on how endocytic trafficking of signaling components (e.g., ligands or receptors) controls the generation, propagation, modulation, reception, and interpretation of developmental signals. A comprehensive enumeration of the links between endocytosis and signal transduction would exceed the limits of this review. We will instead use examples from different developmental pathways to conceptually illustrate the various functions provided by endocytic processes during key steps of intercellular signaling. PMID:24591521

[Estimation of the biological age in taiga tick females (Ixodes persulcatus:Ixodidae) by the fat reserves in organism].

PubMed

Balashov, Iu S; Grigor'eva, L A

2010-01-01

The method of estimation of the biological age in non-feeding tick females by the level of adipose inclusions in the cells of the midgut and fat body is developed. In order to estimate the fat reserves in non-feeding females, alive ticks were dissected and fragments of their internal were vitally stained with the pregnant solution of sudan III in 70 % ethanol. Three age-specific groups were established: I, young females whose intestines and fat body were filled with fat inclusions; II, mature females whose fat reserves were partially expended; III, old females having isolated fat inclusions in their midgut and fat body.

Using Magnetic Forces to Probe the Gravi-response of Swimming Paramecium

NASA Astrophysics Data System (ADS)

Guevorkian, Karine; Valles, James M., Jr.

2004-03-01

Paramecium Caudatum, a single celled ciliate, alters its swimming behavior when subjected to different gravity environments (e.g. centrifugation and micro-gravity). To dissect the mechanisms behind this gravi-response and that of other biological systems, we are developing the use of magnetic body forces as a means of creating a rapidly tunable, simulated variable gravity environment. Since biological materials are weakly diamagnetic, we must subject them to intense inhomogeneous magnetic fields with characteristic field-field gradient products on the order of 16 T^2/cm. We will describe experiments on Paramecium Caudatum in which we adjust their net buoyancy with magnetic forces and measure the resulting changes in their swimming behavior.

Genetics of the extracellular matrix in aortic aneurysmal diseases.

PubMed

Lin, Chien-Jung; Lin, Chieh-Yu; Stitziel, Nathan O

2018-04-12

Aortic aneurysms are morbid conditions that can lead to rupture or dissection and are categorized as thoracic (TAA) or abdominal aortic aneurysms (AAA) depending on their location. While AAA shares overlapping risk factors with atherosclerotic cardiovascular disease, TAA exhibits strong heritability. Human genetic studies in the past two decades have successfully identified numerous genes involved in both familial and sporadic forms of aortic aneurysm. In this review we will discuss the genetic basis of aortic aneurysm, focusing on the extracellular matrix and how insights from these studies have informed our understanding of human biology and disease pathogenesis. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

CT scans and 3D reconstructions of Florida manatee (Trichechus manatus latirostris) heads and ear bones.

PubMed

Chapla, Marie E; Nowacek, Douglas P; Rommel, Sentiel A; Sadler, Valerie M

2007-06-01

The auditory anatomy of the Florida manatee (Trichechus manatus latirostris) was investigated using computerized tomography (CT), three-dimensional reconstructions, and traditional dissection of heads removed during necropsy. The densities (kg/m3) of the soft tissues of the head were measured directly using the displacement method and those of the soft tissues and bone were calculated from CT measurements (Hounsfield units). The manatee's fatty tissue was significantly less dense than the other soft tissues within the head (p<0.05). The squamosal bone was significantly less dense than the other bones of the head (p<0.05). Measurements of the ear bones (tympanic, periotic, malleus, incus, and stapes) collected during dissection revealed that the ossicular chain was overly massive for the mass of the tympanoperiotic complex.

How rare bone diseases have informed our knowledge of complex diseases.

PubMed

Johnson, Mark L

2016-01-01

Rare bone diseases, generally defined as monogenic traits with either autosomal recessive or dominant patterns of inheritance, have provided a rich database of genes and associated pathways over the past 2-3 decades. The molecular genetic dissection of these bone diseases has yielded some major surprises in terms of the causal genes and/or involved pathways. The discovery of genes/pathways involved in diseases such as osteopetrosis, osteosclerosis, osteogenesis imperfecta and many other rare bone diseases have all accelerated our understanding of complex traits. Importantly these discoveries have provided either direct validation for a specific gene embedded in a group of genes within an interval identified through a complex trait genome-wide association study (GWAS) or based upon the pathway associated with a monogenic trait gene, provided a means to prioritize a large number of genes for functional validation studies. In some instances GWAS studies have yielded candidate genes that fall within linkage intervals associated with monogenic traits and resulted in the identification of causal mutations in those rare diseases. Driving all of this discovery is a complement of technologies such as genome sequencing, bioinformatics and advanced statistical analysis methods that have accelerated genetic dissection and greatly reduced the cost. Thus, rare bone disorders in partnership with GWAS have brought us to the brink of a new era of personalized genomic medicine in which the prevention and management of complex diseases will be driven by the molecular understanding of each individuals contributing genetic risks for disease.

New Paradigms and Improved Results for the Surgical Treatment of Acute Type A Dissection

PubMed Central

Bavaria, Joseph E.; Pochettino, Alberto; Brinster, Derek R.; Gorman, Robert C.; McGarvey, Michael L.; Gorman, Joseph H.; Escherich, Alison; Gardner, Timothy J.

2001-01-01

Objective To examine the effect of an integrated surgical approach to the treatment of acute type A dissections. Summary Background Data Acute type A dissection requires surgery to prevent death from proximal aortic rupture or malperfusion. Most series of the past decade have reported a death rate in the range of 15% to 30%. Methods From January 1994 to March 2001, 104 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) to replace the aortic arch; HCA established after 5 minutes of electroencephalographic (EEG) silence in neuromonitored patients (66%) or after 45 minutes of cooling in patients who were not neuromonitored (34%); reinforcement of the residual arch tissue with a Teflon felt “neo-media”; cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt “neo-media” and aortic valve resuspension (78%) or replacement with a biologic or mechanical valved conduit (22%). Results Mean age was 59 ± 15 (range 22–86) years, with 71% men and 13% redo sternotomy after a previous cardiac procedure. Mean cardiopulmonary bypass time was 196 ± 50 minutes. Mean HCA with RCP time was 42 ± 12 minutes (range 19–84). Mean cardiac ischemic time was 140 ± 45 minutes. Eleven percent of patients presented with a preoperative neurologic deficit, and 5% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9%. Excluding the patients who presented neurologically unresponsive or with ongoing cardiopulmonary resuscitation (n = 5), the death rate was 4%. In six patients adverse cerebral outcomes were potentially avoided when immediate surgical fenestration was prompted by a sudden change in the EEG during cooling. Forty-five percent of neuromonitored patients required greater than 30 minutes to achieve EEG silence. Conclusion The authors have shown that the surgical integration of sinus segment repair or aortic root replacement, the use of EEG monitoring, partial or total arch replacement using RCP, routine antegrade graft perfusion, and the uniform use of transesophageal echocardiography substantially decrease the death and complication rates of acute type A dissection repair. PMID:11524586

Minilaparoscopic technique for inguinal hernia repair combining transabdominal pre-peritoneal and totally extraperitoneal approaches.

PubMed

Carvalho, Gustavo L; Loureiro, Marcelo P; Bonin, Eduardo A; Claus, Christiano P; Silva, Frederico W; Cury, Antonio M; Fernandes, Flavio A M

2012-01-01

Endoscopic surgical repair of inguinal hernia is currently conducted using 2 techniques: the totally extraperitoneal (TEP) and the transabdominal (TAPP) hernia repair. The TEP procedure is technically advantageous, because of the use of no mesh fixation and the elimination of the peritoneal flap, leading to less postoperative pain and faster recovery. The drawback is that TEP is not performed as frequently, because of its complexity and longer learning curve. In this study, we propose a hybrid technique that could potentially become the gold standard of minimally invasive inguinal hernia surgery. This will be achieved by combining established advantages of TEP and TAPP associated with the precision and cosmetics of minilaparoscopy (MINI). Between January and July 2011, 22 patients were admitted for endoscopic inguinal hernia repair. The combined technique was initiated with TAPP inspection and direct visualization of a minilaparoscopic trocar dissection of the preperitoneum space. A10-mm trocar was then placed inside the previously dissected preperitoneal space, using the same umbilical TAPP skin incision. Minilaparoscopic retroperitoneal dissection was completed by TEP, and the surgical procedure was finalized with intraperitoneal review and correction of the preperitoneal work. The minilaparoscopic TEP-TAPP combined approach for inguinal hernia is feasible, safe, and allows a simple endoscopic repair. This is achieved by combining features and advantages of both TAPP and TEP techniques using precise and sophisticated MINI instruments. Minilaparoscopic preperitoneal dissection allows a faster and easier creation of the preperitoneal space for the TEP component of the procedure.

SCAR/WAVE: A complex issue.

PubMed

Davidson, Andrew J; Insall, Robert H

2013-11-01

The SCAR/WAVE complex drives the actin polymerisation that underlies protrusion of the front of the cell and thus drives migration. However, it is not understood how the activity of SCAR/WAVE is regulated to generate the infinite range of cellular shape changes observed during cell motility. What are the relative roles of the subunits of the SCAR/WAVE complex? What signaling molecules do they interact with? And how does the complex integrate all this information in order to control the temporal and spatial polymerisation of actin during protrusion formation? Unfortunately, the interdependence of SCAR complex members has made genetic dissection hard. In our recent paper,(1) we describe stabilization of the Dictyostelium SCAR complex by a small fragment of Abi. Here we summarize the main findings and discuss how this approach can help reveal the inner workings of this impenetrable complex.

Using Checklists in a Gross Anatomy Laboratory Improves Learning Outcomes and Dissection Quality

ERIC Educational Resources Information Center

Hofer, Ryan Engebretson; Nikolaus, O. Brant; Pawlina, Wojciech

2011-01-01

Checklists have been widely used in the aviation industry ever since aircraft operations became more complex than any single pilot could reasonably remember. More recently, checklists have found their way into medicine, where cognitive function can be compromised by stress and fatigue. The use of checklists in medical education has rarely been…

An Appreciation and Analysis of "Edward Burtynsky--Manufactured Landscapes": A Film by Jennifer Baichwal

ERIC Educational Resources Information Center

Donar, Ann

2010-01-01

This article begins with a synopsis of the film "Edward Burtynsky: Manufactured Landscapes", directed by Jennifer Baichwal. While the author can relate to the statements made in this synopsis, her experience and understanding of this 90-minute journey is much more intense and complex. In this essay, she attempts to dissect and examine…

Molecular dissection of white pine genetic resistance to Cronartium ribicola

Treesearch

Jun-Jun Liu; Richard Sniezko

2011-01-01

Pinus monticola (Dougl. ex D. Don.) maintains a complex defence system that detects white pine blister rust pathogen (Cronartium ribicola J.C.Fisch.) and activates resistance responses. A thorough understanding of how it functions at the molecular level would provide us new strategies for creating forest trees with durable disease resistance. Our research focuses on...

The Role of Personality and Team-Based Product Dissection on Fixation Effects

ERIC Educational Resources Information Center

Toh, Christine; Miller, Scarlett; Kremer, Gül E. Okudan

2013-01-01

Design fixation has been found to be complex in its definition and expression, but it plays an important role in design idea generation. Identifying the factors that influence fixation is crucial in understanding how to enhance the design process and reduce the negative effects of fixation. One way to potentially mitigate fixation is through…

Teaching Anatomy and Physiology Using Computer-Based, Stereoscopic Images

ERIC Educational Resources Information Center

Perry, Jamie; Kuehn, David; Langlois, Rick

2007-01-01

Learning real three-dimensional (3D) anatomy for the first time can be challenging. Two-dimensional drawings and plastic models tend to over-simplify the complexity of anatomy. The approach described uses stereoscopy to create 3D images of the process of cadaver dissection and to demonstrate the underlying anatomy related to the speech mechanisms.…

The Cranial Nerve Skywalk: A 3D Tutorial of Cranial Nerves in a Virtual Platform

ERIC Educational Resources Information Center

Richardson-Hatcher, April; Hazzard, Matthew; Ramirez-Yanez, German

2014-01-01

Visualization of the complex courses of the cranial nerves by students in the health-related professions is challenging through either diagrams in books or plastic models in the gross laboratory. Furthermore, dissection of the cranial nerves in the gross laboratory is an extremely meticulous task. Teaching and learning the cranial nerve pathways…

A Toxoplasma MORN1 Null Mutant Undergoes Repeated Divisions but Is Defective in Basal Assembly, Apicoplast Division and Cytokinesis

PubMed Central

Lorestani, Alexander; Sheiner, Lilach; Yang, Kevin; Robertson, Seth D.; Sahoo, Nivedita; Brooks, Carrie F.; Ferguson, David J. P.; Striepen, Boris; Gubbels, Marc-Jan

2010-01-01

The membrane occupation and recognition nexus protein 1 (MORN1) is highly conserved among apicomplexan parasites and is associated with several structures that have a role in cell division. Here we dissected the role of MORN1 using the relatively simple budding process of Toxoplasma gondii as a model. Ablation of MORN1 in a conditional null mutant resulted in pronounced defects suggesting a central role for MORN1 in apicoplast segregation and in daughter cell budding. Lack of MORN1 resulted in double-headed parasites. These Janus-headed parasites form two complete apical complexes but fail to assemble a basal complex. Moreover, these parasites were capable of undergoing several more budding rounds resulting in the formation of up to 16-headed parasites conjoined at the basal end. Despite this segregation defect, the mother's cytoskeleton was completely disassembled in every budding round. Overall this argues that successful completion of the budding is not required for cell cycle progression. None of the known basal complex components, including a set of recently identified inner membrane complex (IMC) proteins, localized correctly in these multi-headed parasites. These data suggest that MORN1 is essential for assembly of the basal complex, and that lack of the basal complex abolishes the contractile capacity assigned to the basal complex late in daughter formation. Consistent with this hypothesis we observe that MORN1 mutants fail to efficiently constrict and divide the apicoplast. We used the null background provided by the mutant to dissect the function of subdomains of the MORN1 protein. This demonstrated that deletion of a single MORN domain already prevented the function of MORN1 whereas a critical role for the short linker between MORN domains 6 and 7 was identified. In conclusion, MORN1 is required for basal complex assembly and loss of MORN1 results in defects in apicoplast division and daughter segregation. PMID:20808817

Future of cell and gene therapies for Parkinson's disease.

PubMed

Isacson, Ole; Kordower, Jeffrey H

2008-12-01

The experimental field of restorative neurology continues to advance with implantation of cells or transfer of genes to treat patients with neurological disease. Both strategies have generated a consensus that demonstrates their capacity for structural and molecular brain modification in the adult brain. However, both approaches have yet to successfully address the complexities to make such novel therapeutic modalities work in the clinic. Prior experimental cell transplantation to patients with PD utilized dissected pieces of fetal midbrain tissue, containing mixtures of cells and neuronal types, as donor cells. Stem cell and progenitor cell biology provide new opportunities for selection and development of large batches of specific therapeutic cells. This may allow for cell composition analysis and dosing to optimize the benefit to an individual patient. The biotechnology used for cell and gene therapy for treatment of neurological disease may eventually be as advanced as today's pharmaceutical drug-related design processes. Current gene therapy phase 1 safety trials for PD include the delivery of a growth factor (neurturin via the glial cell line-derived neurotrophic factor receptor) and a transmitter enzyme (glutamic acid decarboxylase and aromatic acid decarboxylase). Many new insights from cell biological and molecular studies provide opportunities to selectively express or suppress factors relevant to neuroprotection and improved function of neurons involved in PD. Future gene and cell therapies are likely to coexist with classic pharmacological therapies because their use can be tailored to individual patients' underlying disease process and need for neuroprotective or restorative interventions.

Hidden biodiversity in entomological collections: The overlooked co-occurrence of dipteran and hymenopteran ant parasitoids in stored biological material

PubMed Central

Pérez-Lachaud, Gabriela

2017-01-01

Biological collections around the world are the repository of biodiversity on Earth; they also hold a large quantity of unsorted, unidentified, or misidentified material and can house behavioral information on species that are difficult to access or no longer available to science. Among the unsorted, alcohol-preserved material stored in the Formicidae Collection of the ‘El Colegio de la Frontera Sur’ Research Center (Chetumal, Mexico), we found nine colonies of the ponerine ant Neoponera villosa, that had been collected in bromeliads at Calakmul (Campeche, Mexico) in 1999. Ants and their brood were revised for the presence of any sign of parasitism. Cocoons were dissected and their content examined under a stereomicroscope. Six N. villosa prepupae had been attacked by the ectoparasitoid syrphid fly Hypselosyrphus trigonus Hull (Syrphidae: Microdontinae), to date the only known dipteran species of the Microdontinae with a parasitoid lifestyle. In addition, six male pupae from three colonies contained gregarious endoparasitoid wasps. These were specialized in parasitizing this specific host caste as no gyne or worker pupae displayed signs of having been attacked. Only immature stages (larvae and pupae) of the wasp could be obtained. Due to the long storage period, DNA amplification failed; however, based on biological and morphological data, pupae were placed in the Encyrtidae family. This is the first record of an encyrtid wasp parasitizing N. villosa, and the second example of an encyrtid as a primary parasitoid of ants. Furthermore, it is also the first record of co-occurrence of a dipteran ectoparasitoid and a hymenopteran endoparasitoid living in sympatry within the same population of host ants. Our findings highlight the importance of biological collections as reservoirs of hidden biodiversity, not only at the taxonomic level, but also at the behavioral level, revealing complex living networks. They also highlight the need for funding in order to carry out biodiversity inventories and manage existing collections. PMID:28926617

Hidden biodiversity in entomological collections: The overlooked co-occurrence of dipteran and hymenopteran ant parasitoids in stored biological material.

PubMed

Pérez-Lachaud, Gabriela; Lachaud, Jean-Paul

2017-01-01

Biological collections around the world are the repository of biodiversity on Earth; they also hold a large quantity of unsorted, unidentified, or misidentified material and can house behavioral information on species that are difficult to access or no longer available to science. Among the unsorted, alcohol-preserved material stored in the Formicidae Collection of the 'El Colegio de la Frontera Sur' Research Center (Chetumal, Mexico), we found nine colonies of the ponerine ant Neoponera villosa, that had been collected in bromeliads at Calakmul (Campeche, Mexico) in 1999. Ants and their brood were revised for the presence of any sign of parasitism. Cocoons were dissected and their content examined under a stereomicroscope. Six N. villosa prepupae had been attacked by the ectoparasitoid syrphid fly Hypselosyrphus trigonus Hull (Syrphidae: Microdontinae), to date the only known dipteran species of the Microdontinae with a parasitoid lifestyle. In addition, six male pupae from three colonies contained gregarious endoparasitoid wasps. These were specialized in parasitizing this specific host caste as no gyne or worker pupae displayed signs of having been attacked. Only immature stages (larvae and pupae) of the wasp could be obtained. Due to the long storage period, DNA amplification failed; however, based on biological and morphological data, pupae were placed in the Encyrtidae family. This is the first record of an encyrtid wasp parasitizing N. villosa, and the second example of an encyrtid as a primary parasitoid of ants. Furthermore, it is also the first record of co-occurrence of a dipteran ectoparasitoid and a hymenopteran endoparasitoid living in sympatry within the same population of host ants. Our findings highlight the importance of biological collections as reservoirs of hidden biodiversity, not only at the taxonomic level, but also at the behavioral level, revealing complex living networks. They also highlight the need for funding in order to carry out biodiversity inventories and manage existing collections.

Variable-angle epifluorescence microscopy characterizes protein dynamics in the vicinity of plasma membrane in plant cells.

PubMed

Chen, Tong; Ji, Dongchao; Tian, Shiping

2018-03-14

The assembly of protein complexes and compositional lipid patterning act together to endow cells with the plasticity required to maintain compositional heterogeneity with respect to individual proteins. Hence, the applications for imaging protein localization and dynamics require high accuracy, particularly at high spatio-temporal level. We provided experimental data for the applications of Variable-Angle Epifluorescence Microscopy (VAEM) in dissecting protein dynamics in plant cells. The VAEM-based co-localization analysis took penetration depth and incident angle into consideration. Besides direct overlap of dual-color fluorescence signals, the co-localization analysis was carried out quantitatively in combination with the methodology for calculating puncta distance and protein proximity index. Besides, simultaneous VAEM tracking of cytoskeletal dynamics provided more insights into coordinated responses of actin filaments and microtubules. Moreover, lateral motility of membrane proteins was analyzed by calculating diffusion coefficients and kymograph analysis, which represented an alternative method for examining protein motility. The present study presented experimental evidence on illustrating the use of VAEM in tracking and dissecting protein dynamics, dissecting endosomal dynamics, cell structure assembly along with membrane microdomain and protein motility in intact plant cells.

Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy

PubMed Central

Dalma-Weiszhausz, Jose; Franco-Cardenas, Valentina; Dalma, Alejandro

2012-01-01

Proliferative vitreoretinopathy (PVR) is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL) is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis. PMID:23502847

How to establish endoscopic submucosal dissection in Western countries.

PubMed

Oyama, Tsuneo; Yahagi, Naohisa; Ponchon, Thierry; Kiesslich, Tobias; Berr, Frieder

2015-10-28

Endoscopic submucosal dissection (ESD) has been invented in Japan to provide resection for cure of early cancer in the gastrointestinal tract. Professional level of ESD requires excellent staging of early neoplasias with image enhanced endoscopy (IEE) to make correct indications for ESD, and high skills in endoscopic electrosurgical dissection. In Japan, endodiagnostic and endosurgical excellence spread through personal tutoring of skilled endoscopists by the inventors and experts in IEE and ESD. To translocate this expertise to other continents must overcome two fundamental obstacles: (1) inadequate expectations as to the complexity of IEE and ESD; and (2) lack of suitable lesions and master-mentors for ESD trainees. Leading endoscopic mucosal resection-proficient endoscopists must pioneer themselves through the long learning curve to proficient ESD experts. Major referral centers for ESD must arise in Western countries on comparable professional level as in Japan. In the second stage, the upcoming Western experts must commit themselves to teach skilled endoscopists from other referral centers, in order to spread ESD in Western countries. Respect for patients with early gastrointestinal cancer asks for best efforts to learn endoscopic categorization of early neoplasias and skills for ESD based on sustained cooperation with the masters in Japan. The strategy is discussed here.

Virtual dissection and lifestyle of a 165 -million-year-old female polychelidan lobster.

PubMed

Jauvion, Clément; Audo, Denis; Charbonnier, Sylvain; Vannier, Jean

2016-03-01

Polychelidan lobsters are fascinating crustaceans that were known as fossils before being discovered in the deep-sea. They differ from other crustaceans by having four to five pairs of claws. Although recent palaeontological studies have clarified the systematics and phylogeny of the group, the biology of extant polychelidans and--first of all--their anatomy are poorly documented. Numerous aspects of the evolutionary history of the group remain obscure, in particular, how and when polychelidans colonized the deep-sea and became restricted to it. Surprisingly, the biology of extant polychelidans and the anatomy of all species, fossil and recent, are poorly documented. Here, X-ray microtomography (XTM), applied to an exceptionally well-preserved specimen from the La Voulte Lagerstätte, reveals for the first time vital aspects of the external and internal morphology of Voulteryon parvulus (Eryonidae), a 165-million-year-old polychelidan: 1) its mouthparts (maxillae and maxillipeds), 2) its digestive tract and 3) its reproductive organs. Comparisons with dissected specimens clearly identify this specimen as a female with mature ovaries. This set of new information offers new insights into the feeding and reproductive habits of Mesozoic polychelidans. Contrasting with other Jurassic polychelidans that lived in shallow-water environments, V. parvulus spawned in, and probably inhabited, relatively deep-water environments, as do the survivors of the group. Copyright © 2015 Elsevier Ltd. All rights reserved.

Deconstructing Memory in Drosophila

PubMed Central

Margulies, Carla; Tully, Tim; Dubnau, Josh

2011-01-01

Unlike most organ systems, which have evolved to maintain homeostasis, the brain has been selected to sense and adapt to environmental stimuli by constantly altering interactions in a gene network that functions within a larger neural network. This unique feature of the central nervous system provides a remarkable plasticity of behavior, but also makes experimental investigations challenging. Each experimental intervention ramifies through both gene and neural networks, resulting in unpredicted and sometimes confusing phenotypic adaptations. Experimental dissection of mechanisms underlying behavioral plasticity ultimately must accomplish an integration across many levels of biological organization, including genetic pathways acting within individual neurons, neural network interactions which feed back to gene function, and phenotypic observations at the behavioral level. This dissection will be more easily accomplished for model systems such as Drosophila, which, compared with mammals, have relatively simple and manipulable nervous systems and genomes. The evolutionary conservation of behavioral phenotype and the underlying gene function ensures that much of what we learn in such model systems will be relevant to human cognition. In this essay, we have not attempted to review the entire Drosophila memory field. Instead, we have tried to discuss particular findings that provide some level of intellectual synthesis across three levels of biological organization: behavior, neural circuitry and biochemical pathways. We have attempted to use this integrative approach to evaluate distinct mechanistic hypotheses, and to propose critical experiments that will advance this field. PMID:16139203

A Critical Analysis of the Current Knowledge of Surgical Anatomy of the Prostate Related to Optimisation of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy: An Update.

PubMed

Walz, Jochen; Epstein, Jonathan I; Ganzer, Roman; Graefen, Markus; Guazzoni, Giorgio; Kaouk, Jihad; Menon, Mani; Mottrie, Alexandre; Myers, Robert P; Patel, Vipul; Tewari, Ashutosh; Villers, Arnauld; Artibani, Walter

2016-08-01

In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy. To provide an update based on new literature to help the surgeon improve oncologic and surgical outcomes of radical prostatectomy (RP). We searched the PubMed database using the keywords radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters published since the last review were critically reviewed, analysed, and summarised. Moreover, we integrated aspects that were not addressed in the last review into this update. We found new evidence for several topics. Up to 40% of the cross-sectional surface area of the urethral sphincter tissue is laterally overlapped by the dorsal vascular complex and might be injured during en bloc ligation. Denonvilliers fascia is fused with the base of the prostate in a horizontal fashion dorsally/caudally of the seminal vesicles, requiring sharp detachment when preserved. During extended pelvic lymph node dissection, the erectile nerves are at risk in the presacral and internal iliac area. Dissection planes for nerve sparing can be graded according to the amount of tissue left on the prostate as a safety margin against positive surgical margins. Vascular structures can serve as landmarks. The urethral sphincter and its length after RP are influenced by the shape of the apex. Taking this shape into account allows preservation of additional sphincter length with improved postoperative continence. This update provides additional, detailed information about the surgical anatomy of the prostate and adjacent tissues involved in RP. This anatomy remains complex and widely variable. These details facilitate surgical orientation and dissection during RP and ideally should translate into improved outcomes. Based on recent anatomic findings regarding the prostate and its surrounding tissue, the urologist can individualise the dissection during RP according to cancer and patient characteristics to improve oncologic and functional results at the same time. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Effect of a Prior Dissection Simulation on Middle School Students' Dissection Performance and Understanding of the Anatomy and Morphology of the Frog

NASA Astrophysics Data System (ADS)

Akpan, Joseph Paul; Andre, Thomas

1999-06-01

Science teachers, school administrators, educators, and the scientific community are faced with ethical controversies over animal dissection in classrooms. Simulation has been proposed as a way of dealing with this issue. One intriguing previous finding was that use of an interactive videodisc dissection facilitated performance on a subsequent actual dissection. This study examined the prior use of simulation of frog dissection in improving students' actual dissection performance and learning of frog anatomy and morphology. There were three experimental conditions: simulation before dissection (SBD); dissection before simulation (DBS); or dissection-only (DO). Results of the study indicated that students receiving SBD performed significantly better than students receiving DBS or DO on both actual dissection and knowledge of the anatomy and morphology. Students' attitudes toward the use of animals for dissection did not change significantly from pretest to posttest and did not interact with treatment. The genders did not differ in achievement, but males were more favorable towards dissection and computers than were females.

Fungal biology and agriculture: revisiting the field

USGS Publications Warehouse

Yarden, O.; Ebbole, D.J.; Freeman, S.; Rodriguez, R.J.; Dickman, M. B.

2003-01-01

Plant pathology has made significant progress over the years, a process that involved overcoming a variety of conceptual and technological hurdles. Descriptive mycology and the advent of chemical plant-disease management have been followed by biochemical and physiological studies of fungi and their hosts. The later establishment of biochemical genetics along with the introduction of DNA-mediated transformation have set the stage for dissection of gene function and advances in our understanding of fungal cell biology and plant-fungus interactions. Currently, with the advent of high-throughput technologies, we have the capacity to acquire vast data sets that have direct relevance to the numerous subdisciplines within fungal biology and pathology. These data provide unique opportunities for basic research and for engineering solutions to important agricultural problems. However, we also are faced with the challenge of data organization and mining to analyze the relationships between fungal and plant genomes and to elucidate the physiological function of pertinent DNA sequences. We present our perspective of fungal biology and agriculture, including administrative and political challenges to plant protection research.

Lipid Cell Biology: A Focus on Lipids in Cell Division.

PubMed

Storck, Elisabeth M; Özbalci, Cagakan; Eggert, Ulrike S

2018-06-20

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA

PubMed Central

Henare, K; Wang, L; Wang, L-Cs; Thomsen, L; Tijono, S; Chen, C-Jj; Winkler, S; Dunbar, P R; Print, C; Ching, L-M

2012-01-01

Background: The non-malignant cells of the tumour stroma have a critical role in tumour biology. Studies dissecting the interplay between cancer cells and stromal cells are required to further our understanding of tumour progression and methods of intervention. For proof-of-principle of a multi-modal approach to dissect the differential effects of treatment on cancer cells and stromal cells, we analysed the effects of the stromal-targeting agent 5,6-dimethylxanthenone-4-acetic acid on melanoma xenografts. Methods: Flow cytometry and multi-colour immunofluorescence staining was used to analyse leukocyte numbers in xenografts. Murine-specific and human-specific multiplex cytokine panels were used to quantitate cytokines produced by stromal and melanoma cells, respectively. Human and mouse Affymetrix microarrays were used to separately identify melanoma cell-specific and stromal cell-specific gene expression. Results: 5,6-Dimethylxanthenone-4-acetic acid activated pro-inflammatory signalling pathways and cytokine expression from both stromal and cancer cells, leading to neutrophil accumulation and haemorrhagic necrosis and a delay in tumour re-growth of 26 days in A375 melanoma xenografts. Conclusion: 5,6-Dimethylxanthenone-4-acetic acid and related analogues may potentially have utility in the treatment of melanoma. The experimental platform used allowed distinction between cancer cells and stromal cells and can be applied to investigate other tumour models and anti-cancer agents. PMID:22415295

Should hidradenitis suppurativa/acne inversa best be renamed as "dissecting terminal hair folliculitis"?

PubMed

Chen, WenChieh; Plewig, Gerd

2017-06-01

Hidradenitis suppurativa/acne inversa is a diverse, enigmatic and distressful disease that has aroused growing interest in specialists from different disciplines. Both names describe its classical manifestations in the intertriginous regions and reflect the historical view of the disease definition, but cause confusions in the understanding of its pathogenesis and classification. In the light of the advance in clinical, histopathological and pathophysiological findings, we propose the term "dissecting terminal hair folliculitis" (DTHF) to characterize its disease nature as folliculitis instead of acneiform disease or apocrine gland disorder. DTHF attacks exclusively the terminal hair follicles in an overwhelming majority of adults, initiating from the fragile acroinfundibulum leading to a non-infectious overreaction of innate immunity system with inflammation that may fiercely dissect and engulf all the surrounding tissues accompanied by secondary bacterial infections. Evidence indicates that perifolliculitis capitis abscedens et suffodiens and pilonidal disease are very likely regional variants of DTHF with the same pathogenesis. Treatment of DTHF remains frustrating. The benefit of biologics in targeting inflammation is so far non-specific, palliative and inconsistent. Hair epilation and photodynamic therapy in treatment of the disease is questionable in consideration of the pathogenesis. Genetic and translational research, especially on the Notch signalling pathways, will yield breakthrough in the development of novel treatment modalities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Secondary science classroom dissections: Informing policy by evaluating cognitive outcomes and exploring affective outcomes

NASA Astrophysics Data System (ADS)

Allspaw, Kathleen M.

Animal protection organizations claim that dissection is pedagogically unsound and that it will cause students to lose respect for non-human animals. Science teacher organizations support curricula that teach respect for animal life and include dissection. Prior research compared dissection to dissection alternatives. Four of the six studies revealed no difference between groups on tests of cognitive outcomes. One study revealed that dissection was superior, and one revealed that the alternative was superior. No differences in attitudes toward science, dissection or school were found. Attitudes toward non-human animals were not measured. This study focused on the dissections of earthworms and frogs in middle and high school classrooms. Pre and post-tests of conceptual understanding revealed failing scores and no significant pre/post differences. Because these tests required critical thinking skills, and the dissection activities did not, it is difficult to determine if the poor performance on these tests indicates the inability of the students to think critically, and/or if it indicates the ineffectiveness of dissection. Further studies of dissections that focus on critical thinking would be necessary to make this distinction. Classroom observations, student written narratives, and student and adult interviews revealed mixed attitudes toward non-human animals. Student behaviors during dissection were similar to those behaviors exhibited during non-dissection activities. Most students and adults readily supported worm dissections while they expressed some trepidation about frog dissections. Students and adults universally expressed affection for their pets and opposed the use of their own pets for dissection/research. There was slight support for the use of dogs and cats for dissection/research, but only those students who expressed hate for cats said that they could dissect cats. None of the students or adults expressed a willingness to dissect dogs. Some students abandoned plans for life science careers because they did not want to do further dissections. Students and adults often expressed confliction about the use of animals for food and/or research. Students and adults employed psychological mechanisms including dissociation, conflict reduction and viewing animals as an "outgroup" to rationalize their support for the use of animals for food, dissection and research.

Processes that Drove the Transition from Chemistry to Biology: Concepts and Evidence

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2012-01-01

Two properties are particularly germane to the transition from chemistry to biology. One is the emergence of complex molecules (polymers) capable of performing non-trivial functions, such as catalysis, energy transduction or transport across cell walls. The other is the ability of several functions to work in concert to provide reproductive advantage to systems hosting these functions. Biological systems exhibit these properties at remarkable levels of efficiency and accuracy in a way that appears effortless. However, dissection of these properties reveals great complexities that are involved. This opens a question: how a simple, ancestral system could have acquired the required properties? Other questions follow. What are the chances that a functional polymer emerges at random? What is the minimum structural complexity of a polymer to carry out a function at a reasonable level of efficiency? Can we identify concrete, protobiologically plausible mechanisms that yield advantageous coupling between different functions? These and similar questions are at the core of the main topic of this session: how soulless chemistry became life? Clearly, we do not have complete answers to any of these questions. However, in recent years a number of new and sometimes unexpected clues have been brought to light. Of particular interest are proteins because they are the main functional polymers in contemporary cells. The emergence of protein functions is a puzzle. It is widely accepted that a well ]defined, compact structure (fold) is a prerequisite for function. It is equally widely accepted that compact folds are rare among random amino acid polymers. Then, how did protein functionality start? According to one hypothesis well folded were preceded by their poorly folded, yet still functional ancestors. Only recently, however, experimental evidence supporting this hypothesis has been presented. In particular, a small enzyme capable of ligating two RNA fragments with the rate of 106 above background was evolved in vitro. This enzyme does not look like any contemporary protein. It is very flexible and its structure is kept together just by a single salt bridge between a charged residue and a coordinating zinc. A similar picture emerges from studies of simple transmembrane channels that mimic those in ancestral cells. Again, they are extremely flexible and do not form a conventional pore. Yet, they efficiently mediate ion transport. Studies on simple proteins that are on-going in several laboratories hold promise of revealing crucial links between chemical and biological catalysis and other ubiquitous cell functions. Interaction between composition, growth and division of protobiologically relevant vesicles and metabolic reactions that they encapsulate is an example of coupling between simple functions that promotes reproduction and evolution. Recent studies have demonstrated possible mechanisms by which vesicles might have evolved their composition from fatty acids to phospholipids, thus facilitating a number of new cellular functions. Conversely, it has been also demonstrated that an encapsulated metabolism might drive vesicle division. These are, again, examples of processes that might have driven the transition from chemistry to biology.

Dissection and engineering of the Escherichia coli formate hydrogenlyase complex.

PubMed

McDowall, Jennifer S; Hjersing, M Charlotte; Palmer, Tracy; Sargent, Frank

2015-10-07

The Escherichia coli formate hydrogenlyase (FHL) complex is produced under fermentative conditions and couples formate oxidation to hydrogen production. In this work, the architecture of FHL has been probed by analysing affinity-tagged complexes from various genetic backgrounds. In a successful attempt to stabilize the complex, a strain encoding a fusion between FdhF and HycB has been engineered and characterised. Finally, site-directed mutagenesis of the hycG gene was performed, which is predicted to encode a hydrogenase subunit important for regulating sensitivity to oxygen. This work helps to define the core components of FHL and provides solutions to improving the stability of the enzyme. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Basal cell carcinoma of the nipple-areola complex: a case report.

PubMed

Huang, Ching-Wen; Pan, Ching-Kuen; Shih, Teng-Fu; Tsai, Cheng-Chien; Juan, Chung-Chou; Ker, Chen-Guo

2005-10-01

Basal cell carcinoma (BCC) of the nipple-areola complex is very rare. Only 24 cases were reported in the literature and 17 (70.8%) of these cases arose in men. Most of the cases were treated with simple excision. We report on a case of BCC of the nipple-areola complex in a 46-year-old woman, treated with partial mastectomy. Metastasis to the axillary lymph nodes had been noted in 3 (12.5%) of the 24 reported cases of BCC of the nipple-areola complex. Thus, we applied the concept of the sentinel lymph node to detect possible metastases of axillary lymph nodes, letting us avoid the unnecessary axillary lymph node dissection and possible future morbidity.

An integrated bioinformatics analysis to dissect kinase dependency in triple negative breast cancer.

PubMed

Ryall, Karen A; Kim, Jihye; Klauck, Peter J; Shin, Jimin; Yoo, Minjae; Ionkina, Anastasia; Pitts, Todd M; Tentler, John J; Diamond, Jennifer R; Eckhardt, S Gail; Heasley, Lynn E; Kang, Jaewoo; Tan, Aik Choon

2015-01-01

Triple-Negative Breast Cancer (TNBC) is an aggressive disease with a poor prognosis. Clinically, TNBC patients have limited treatment options besides chemotherapy. The goal of this study was to determine the kinase dependency in TNBC cell lines and to predict compounds that could inhibit these kinases using integrative bioinformatics analysis. We integrated publicly available gene expression data, high-throughput pharmacological profiling data, and quantitative in vitro kinase binding data to determine the kinase dependency in 12 TNBC cell lines. We employed Kinase Addiction Ranker (KAR), a novel bioinformatics approach, which integrated these data sources to dissect kinase dependency in TNBC cell lines. We then used the kinase dependency predicted by KAR for each TNBC cell line to query K-Map for compounds targeting these kinases. We validated our predictions using published and new experimental data. In summary, we implemented an integrative bioinformatics analysis that determines kinase dependency in TNBC. Our analysis revealed candidate kinases as potential targets in TNBC for further pharmacological and biological studies.

Ultrasound-Guided Percutaneous Tenotomy of Biceps Tendon: Technical Feasibility on Cadavers.

PubMed

Sconfienza, Luca Maria; Mauri, Giovanni; Messina, Carmelo; Aliprandi, Alberto; Secchi, Francesco; Sardanelli, Francesco; Randelli, Pietro Simone

2016-10-01

We tested the technical feasibility of ultrasound-guided percutaneous tenotomy of the long head of the biceps tendon (LHBT) in cadavers. Both shoulders of two fresh cadavers were scanned anteriorly to evaluate the extra-articular portion of the LHBT. Under ultrasound monitoring, a scalpel was advanced obliquely up to touch the superficial medial side of the LHBT, cutting it until the tendon was not visible anymore. Ultrasound evaluation was repeated after the procedure, and anatomic dissection was performed. The procedure was 100% feasible: four cuts were made to completely sever the tendon; the duration was less than 1 min. Skin incision measured 5 mm in two cases and 6 mm in two cases. Anatomic dissection confirmed complete tendon cut in all cases with proximal and distal tendon stumps very close to each other. Ultrasound-guided percutaneous LHBT tenotomy was 100% technically feasible in cadavers with a quick procedure and minimal cutaneous incision. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Bodily experiences in secondary school biology

NASA Astrophysics Data System (ADS)

Orlander, Auli Arvola; Wickman, Per-Olof

2011-09-01

This is a study of teaching about the human body. It is based on transcribed material from interviews with 15-year-old students and teachers about their experiences of sex education and from recordings of classroom interactions during a dissection. The analysis is focused on the relationship between what students are supposed to learn about the biological body and their expressed experiences and meaning making of bodies in the schoolwork. The results indicate that the negotiations associated with the encounters between the bodies of the classroom (student, teacher, and animal bodies) are important for what directions meaning making takes and what students are afforded to learn about bodies, biologically as well as in terms of values. We suggest that these negotiations should be taken into account at schools, be regarded as an important part of the learning processes in science education and in that way open up for new possibilities for students' meaning making.

Development of Carbocyanine Dyes for PRMT Inhibition and Imaging

PubMed Central

Sinha, Sarmistha Halder; Owens, Eric A.; Feng, You; Yang, Yutao; Xie, Yan; Tu, Yaping; Henary, Maged; Zheng, Yujun George

2014-01-01

Summary Protein arginine methylation regulates multiple biological processes. Deregulation of protein arginine methyltransferase (PRMT) activities has been observed in many disease phenotypes. Small molecule probes that target PRMTs with strong affinity and selectivity can be used as valuable tools to dissect biological mechanisms of arginine methylation and establish the role of PRMT proteins in a disease process. In this work, we report synthesis and evaluation of a class of carbocyanine compounds containing indolium, benz[e]indolium or benz[c,d]indolium heterocyclic moieties that bind to the predominant arginine methyltransferase PRMT1 and inhibit its methyltransferase activity at low micromolar potencies. In particular, the developed molecules have long wavelength colorimetric and fluorometric photoactivities, which can be used for optical and near-infrared fluorescence imaging in cells or biological tissues. Together, these new chemical probes have potential application in PRMT studies both as enzyme inhibitors and as fluorescent dyes for microscope imaging. PMID:22749641

At the cutting edge: applications and perspectives of laser nanosurgery in cell biology.

PubMed

Ronchi, Paolo; Terjung, Stefan; Pepperkok, Rainer

2012-04-01

Laser-mediated nanosurgery has become popular in the last decade because of the previously unexplored possibility of ablating biological material inside living cells with sub-micrometer precision. A number of publications have shown the potential applications of this technique, ranging from the dissection of sub-cellular structures to surgical ablations of whole cells or tissues in model systems such as Drosophila melanogaster or Danio rerio . In parallel, the recent development of micropatterning techniques has given cell biologists the possibility to shape cells and reproducibly organize the intracellular space. The integration of these two techniques has only recently started yet their combination has proven to be very interesting. The aim of this review is to present recent applications of laser nanosurgery in cell biology and to discuss the possible developments of this approach, particularly in combination with micropattern-mediated endomembrane organization.

Microgravity research in plant biological systems: Realizing the potential of molecular biology

NASA Technical Reports Server (NTRS)

Lewis, Norman G.; Ryan, Clarence A.

1993-01-01

The sole all-pervasive feature of the environment that has helped shape, through evolution, all life on Earth is gravity. The near weightlessness of the Space Station Freedom space environment allows gravitational effects to be essentially uncoupled, thus providing an unprecedented opportunity to manipulate, systematically dissect, study, and exploit the role of gravity in the growth and development of all life forms. New and exciting opportunities are now available to utilize molecular biological and biochemical approaches to study the effects of microgravity on living organisms. By careful experimentation, we can determine how gravity perception occurs, how the resulting signals are produced and transduced, and how or if tissue-specific differences in gene expression occur. Microgravity research can provide unique new approaches to further our basic understanding of development and metabolic processes of cells and organisms, and to further the application of this new knowledge for the betterment of humankind.

O-GlcNAc transferase inhibitors: current tools and future challenges.

PubMed

Trapannone, Riccardo; Rafie, Karim; van Aalten, Daan M F

2016-02-01

The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O-GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges. © 2016 Authors; published by Portland Press Limited.

A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection.

PubMed

Nguyen, Daniel P; Huber, Philipp M; Metzger, Tobias A; Genitsch, Vera; Schudel, Hans H; Thalmann, George N

2016-11-01

Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND. Copyright © 2016. Published by Elsevier B.V.

Aortic arch/elephant trunk procedure with Sienna(TM) graft and endovascular stenting of thoraco-abdominal aorta for treatment of complex chronic dissection.

PubMed

Wong, Randolph H L; Baghai, Max; Yu, Simon C H; Underwood, Malcolm J

2013-05-01

Aneurismal dilatation of the remaining thoracic aorta after ascending aortic interposition grafting for type 'A' aortic dissection is not uncommon. For such complex cases, one treatment option is total arch replacement and elephant trunk procedure with the Sienna(TM) collared graft (Vascutek, Inchinnan, UK) technique followed by a staged thoracic endovascular aortic repair (TEVAR). The video illustrates our technique in a 56-year-old man with an extensive aortic arch and descending thoracic aortic dissecting aneurysm. For the 'open' procedure femoral arterial and venous cannulation was used along with systemic cooling and circulatory arrest at 22 °C. Upon circulatory arrest, the aortic arch was incised and antegrade cerebral perfusion achieved via selective cannulation to the right brachiocephalic and left common carotid artery, keeping flow rates at 10-15 mL/kg/min and perfusion pressure at 50-60 mmHg. Arch replacement with an elephant trunk component was then performed and after completion of the distal aortic anastomosis antegrade perfusion via a side-arm in the graft was started and the operation completed using a variation of the 'sequential' clamping technique to maximize cerebral perfusion. The second endovascular stage was performed two weeks after discharge. Two covered stents were landing from the elephant trunk to the distal descending thoracic aorta, to secure the distal landing a bare stent of was placed to cover the aorta just distal to the origin of the celiac axis. The left subclavian artery was embolised with fibre coils. Post TEVAR angiogram showed no endoleak Although re-operative total arch replacement and elephant trunk procedure and subsequent TEVAR remained a challenging procedure, we believe excellent surgical outcome can be achieved with carefully planned operative strategy.

Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

PubMed

Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

2014-12-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology

USDA-ARS?s Scientific Manuscript database

The dissection of complex traits of economic importance for the pig industry requires the availability of a significant number of genetic markers, such as SNPs. This study was conducted in order to discover thousands of porcine SNPs using next generation sequencing technologies and use those SNPs, a...

Dissection of Host Susceptibility to Bacterial Infections and Its Toxins.

PubMed

Nashef, Aysar; Agbaria, Mahmoud; Shusterman, Ariel; Lorè, Nicola Ivan; Bragonzi, Alessandra; Wiess, Ervin; Houri-Haddad, Yael; Iraqi, Fuad A

2017-01-01

Infection is one of the leading causes of human mortality and morbidity. Exposure to microbial agents is obviously required. However, also non-microbial environmental and host factors play a key role in the onset, development and outcome of infectious disease, resulting in large of clinical variability between individuals in a population infected with the same microbe. Controlled and standardized investigations of the genetics of susceptibility to infectious disease are almost impossible to perform in humans whereas mouse models allow application of powerful genomic techniques to identify and validate causative genes underlying human diseases with complex etiologies. Most of current animal models used in complex traits diseases genetic mapping have limited genetic diversity. This limitation impedes the ability to create incorporated network using genetic interactions, epigenetics, environmental factors, microbiota, and other phenotypes. A novel mouse genetic reference population for high-resolution mapping and subsequently identifying genes underlying the QTL, namely the Collaborative Cross (CC) mouse genetic reference population (GRP) was recently developed. In this chapter, we discuss a variety of approaches using CC mice for mapping genes underlying quantitative trait loci (QTL) to dissect the host response to polygenic traits, including infectious disease caused by bacterial agents and its toxins.

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

PubMed Central

Terasaki, Kaori; Ramirez, Sydney I.; Makino, Shinji

2016-01-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence. PMID:27711108

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence.

PubMed

Terasaki, Kaori; Ramirez, Sydney I; Makino, Shinji

2016-10-01

Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.

Laparoscopic pancreatoduodenectomy with superior mesenteric artery-first approach and pancreatogastrostomy assisted by mini-laparotomy.

PubMed

Zimmitti, Giuseppe; Manzoni, Alberto; Addeo, Pietro; Garatti, Marco; Zaniboni, Alberto; Bachellier, Philippe; Rosso, Edoardo

2016-04-01

Laparoscopic pancreatoduodenectomy (LPD) is a complex procedure. Critical steps are achieving a negative retroperitoneal margin and re-establishing pancreatoenteric continuity minimizing postoperative pancreatic leak risk. Aiming at increasing the rate of R0 resection during pancreatoduodenectomy, many experienced teams have recommended the superior mesenteric artery (SMA)-first approach, consisting in early identification of the SMA at its origin, with further resection guided by SMA anatomic course. We describe our technique of LPD with SMA-first approach and pancreatogastrostomy assisted by mini-laparotomy. The video concerns a 77-year-old man undergoing our variant of LPD for a 2.5-cm pancreatic head mass. After kocherization, the SMA is identified above the left renocaval confluence and dissected-free from the surrounding tissue. Dissection of the posterior pancreatic aspect exposes the confluence between splenic vein, superior mesenteric vein (SMV), and portal vein. Following duodenal section, the common hepatic artery is dissected and the gastroduodenal artery sectioned at the origin. The first jejunal loop is divided, skeletonized, and passed behind the superior mesenteric vessel. Following pancreatic transection, the uncinate process is dissected from the SMV and the SMA is cleared from retroportal tissue rejoining the previously dissected plain. Laparoscopic choledocojejunostomy is followed by a mini-laparotomy-assisted pancreatogastrostomy, performed as previously described, and a terminolateral gastrojejeunostomy. Twelve patients underwent our variant of LPD (July 2013-May 2015). Female/male ratio was 3:1, median age 65 years (range 57-79), median operation duration 590 min (580-690), intraoperative blood loss 150 cl (100-250). R0 resection rate was 100 %, and the median number of resected lymph nodes was 24 (22-28). Postoperative complications were grade II in two patients and IIIa in one. Median postoperative length of stay was 16 days (14-21). LPD with SMA-first approach with pancreatogastrostomy assisted by a mini-laparotomy well combines the benefits of laparoscopy with low risk of postoperative complications and high rate of curative resection.

Microsurgical resection of intramedullary spinal cord ependymoma.

PubMed

McCormick, Paul C

2014-09-01

Ependymomas are the most commonly occurring intramedullary spinal cord tumor in adults. With few exceptions these tumors are histologically benign, although they exhibit some biologic variability with respect to growth rate. While unencapsulated, spinal ependymomas are non-infiltrative and present a clear margin of demarcation from the surrounding spinal cord that serves as an effective dissection plane. This video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU.

Primary Pulmonary Mucinous Cystadenocarcinoma: A Case Report

PubMed Central

Efstathiou, Andreas; Asteriou, Christos; Barbetakis, Nikolaos; Miliaras, Dimosthenis; Kleontas, Athanassios; Karvelas, Christos; Lalountas, Miltiadis

2011-01-01

Primary pulmonary mucinous cystadenocarcinoma (PMCAC) is an extremely rare cystic neoplasm. A case of a 56-year-old male with a cystic lesion of the right lower lobe is described. Preoperative fine needle aspiration cytology and bronchoscopy were inconclusive. The patient underwent a formal right lower lobectomy and mediastinal lymph node dissection. Diagnosis was established intraoperatively. The biological behavior of primary PMCAC is unknown. Therefore, careful long-term follow-up is considered necessary because of lack of experience globally. PMID:21541179

Photoreactive Stapled BH3 Peptides to Dissect the BCL-2 Family Interactome

PubMed Central

Braun, Craig R.; Mintseris, Julian; Gavathiotis, Evripidis; Bird, Gregory H.; Gygi, Steven P.; Walensky, Loren D.

2010-01-01

SUMMARY Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α-helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design. PMID:21168768

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A postdoctoral position is available in the Viral Recombination Section (VRS), HIV Dynamics and Replication Program, CCR.  The VRS studies retroviral replication using human immunodeficiency viruses and other retroviruses, with a particular emphasis on the mechanisms of viral RNA biology, specific RNA packaging, virus assembly, and HIV replication.  Molecular tools and advanced imaging approaches are used to dissect various aspects of viral replication mechanisms.  A more complete description of the projects can be found at http://home.ncifcrf.gov/hivdrp/Hu_res.html.

Exploring Autophagy in Drosophila

PubMed Central

Juhász, Gábor

2017-01-01

Autophagy is a catabolic process in eukaryotic cells promoting bulk or selective degradation of cellular components within lysosomes. In recent decades, several model systems were utilized to dissect the molecular machinery of autophagy and to identify the impact of this cellular “self-eating” process on various physiological and pathological processes. Here we briefly discuss the advantages and limitations of using the fruit fly Drosophila melanogaster, a popular model in cell and developmental biology, to apprehend the main pathway of autophagy in a complete animal. PMID:28704946

Effect of electrocautery on endothelial integrity of the internal thoracic artery: ultrastructural analysis with transmission electron microscopy.

PubMed

Onan, Burak; Yeniterzi, Mehmet; Onan, Ismihan Selen; Ersoy, Burak; Gonca, Suheyla; Gelenli, Elif; Solakoglu, Seyhun; Bakir, Ihsan

2014-10-01

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. Light microscopic examinations were performed after hematoxylin-eosin and Masson's trichrome staining. Transmission electron microscopy was used to evaluate ultrastructural changes in the endothelial cells and vessel walls of each ITA. In the sharp-dissection group, the endothelial surfaces were lined with normal amounts of original endothelium, endothelial cells were distinctly attached to the basal lamina, cytoplasmic organelles were evident, and intercellular junctional complexes were intact. Conversely, in the electrocautery group, the morphologic integrity of endothelial cells was distorted, with some cell separations and splits, contracted cells, numerous large cytoplasmic vacuoles, and no visible cytoplasmic organelles. The subendothelial layer exhibited disintegration. Free ITA flow was higher in the sharp-dissection group (P=0.04). The integrity of endothelial cells can be better preserved when the ITA is mobilized by means of sharp dissection, rather than solely by electrocautery; we recommend a combined approach.

Effect of Electrocautery on Endothelial Integrity of the Internal Thoracic Artery: Ultrastructural Analysis with Transmission Electron Microscopy

PubMed Central

Onan, Burak; Yeniterzi, Mehmet; Onan, Ismihan Selen; Ersoy, Burak; Gonca, Suheyla; Gelenli, Elif; Solakoglu, Seyhun

2014-01-01

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. Light microscopic examinations were performed after hematoxylin-eosin and Masson's trichrome staining. Transmission electron microscopy was used to evaluate ultrastructural changes in the endothelial cells and vessel walls of each ITA. In the sharp-dissection group, the endothelial surfaces were lined with normal amounts of original endothelium, endothelial cells were distinctly attached to the basal lamina, cytoplasmic organelles were evident, and intercellular junctional complexes were intact. Conversely, in the electrocautery group, the morphologic integrity of endothelial cells was distorted, with some cell separations and splits, contracted cells, numerous large cytoplasmic vacuoles, and no visible cytoplasmic organelles. The subendothelial layer exhibited disintegration. Free ITA flow was higher in the sharp-dissection group (P=0.04). The integrity of endothelial cells can be better preserved when the ITA is mobilized by means of sharp dissection, rather than solely by electrocautery; we recommend a combined approach. PMID:25425979

Molecular mechanisms of aging and immune system regulation in Drosophila.

PubMed

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

The cardiovascular benefits of dark chocolate.

PubMed

Kerimi, Asimina; Williamson, Gary

2015-08-01

Dark chocolate contains many biologically active components, such as catechins, procyanidins and theobromine from cocoa, together with added sucrose and lipids. All of these can directly or indirectly affect the cardiovascular system by multiple mechanisms. Intervention studies on healthy and metabolically-dysfunctional volunteers have suggested that cocoa improves blood pressure, platelet aggregation and endothelial function. The effect of chocolate is more convoluted since the sucrose and lipid may transiently and negatively impact on endothelial function, partly through insulin signalling and nitric oxide bioavailability. However, few studies have attempted to dissect out the role of the individual components and have not explored their possible interactions. For intervention studies, the situation is complex since suitable placebos are often not available, and some benefits may only be observed in individuals showing mild metabolic dysfunction. For chocolate, the effects of some of the components, such as sugar and epicatechin on FMD, may oppose each other, or alternatively in some cases may act together, such as theobromine and epicatechin. Although clearly cocoa provides some cardiovascular benefits according to many human intervention studies, the exact components, their interactions and molecular mechanisms are still under debate. Copyright © 2015 Elsevier Inc. All rights reserved.

Small molecules targeting heterotrimeric G proteins.

PubMed

Ayoub, Mohammed Akli

2018-05-05

G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors regulating many human and animal physiological functions. Their implication in human pathophysiology is obvious with almost 30-40% medical drugs commercialized today directly targeting GPCRs as molecular entities. However, upon ligand binding GPCRs signal inside the cell through many key signaling, adaptor and regulatory proteins, including various classes of heterotrimeric G proteins. Therefore, G proteins are considered interesting targets for the development of pharmacological tools that are able to modulate their interaction with the receptors, as well as their activation/deactivation processes. In this review, old attempts and recent advances in the development of small molecules that directly target G proteins will be described with an emphasis on their utilization as pharmacological tools to dissect the mechanisms of activation of GPCR-G protein complexes. These molecules constitute a further asset for research in the "hot" areas of GPCR biology, areas such as multiple G protein coupling/signaling, GPCR-G protein preassembly, and GPCR functional selectivity or bias. Moreover, this review gives a particular focus on studies in vitro and in vivo supporting the potential applications of such small molecules in various GPCR/G protein-related diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

mRNA expression profiling of laser microbeam microdissected cells from slender embryonic structures.

PubMed

Scheidl, Stefan J; Nilsson, Sven; Kalén, Mattias; Hellström, Mats; Takemoto, Minoru; Håkansson, Joakim; Lindahl, Per

2002-03-01

Microarray hybridization has rapidly evolved as an important tool for genomic studies and studies of gene regulation at the transcriptome level. Expression profiles from homogenous samples such as yeast and mammalian cell cultures are currently extending our understanding of biology, whereas analyses of multicellular organisms are more difficult because of tissue complexity. The combination of laser microdissection, RNA amplification, and microarray hybridization has the potential to provide expression profiles from selected populations of cells in vivo. In this article, we present and evaluate an experimental procedure for global gene expression analysis of slender embryonic structures using laser microbeam microdissection and laser pressure catapulting. As a proof of principle, expression profiles from 1000 cells in the mouse embryonic (E9.5) dorsal aorta were generated and compared with profiles for captured mesenchymal cells located one cell diameter further away from the aortic lumen. A number of genes were overexpressed in the aorta, including 11 previously known markers for blood vessels. Among the blood vessel markers were endoglin, tie-2, PDGFB, and integrin-beta1, that are important regulators of blood vessel formation. This demonstrates that microarray analysis of laser microbeam micro-dissected cells is sufficiently sensitive for identifying genes with regulative functions.

Coastal Seabed Mapping with Hyperspectral and Lidar data

NASA Astrophysics Data System (ADS)

Taramelli, A.; Valentini, E.; Filipponi, F.; Cappucci, S.

2017-12-01

A synoptic view of the coastal seascape and its dynamics needs a quantitative ability to dissect different components over the complexity of the seafloor where a mixture of geo - biological facies determines geomorphological features and their coverage. The present study uses an analytical approach that takes advantage of a multidimensional model to integrate different data sources from airborne Hyperspectral and LiDAR remote sensing and in situ measurements to detect antropogenic features and ecological `tipping points' in coastal seafloors. The proposed approach has the ability to generate coastal seabed maps using: 1) a multidimensional dataset to account for radiometric and morphological properties of waters and the seafloor; 2) a field spectral library to assimilate the high environmental variability into the multidimensional model; 3) a final classification scheme to represent the spatial gradients in the seafloor. The spatial pattern of the response to anthropogenic forcing may be indistinguishable from patterns of natural variability. It is argued that this novel approach to define tipping points following anthropogenic impacts could be most valuable in the management of natural resources and the economic development of coastal areas worldwide. Examples are reported from different sites of the Mediterranean Sea, both from Marine Protected and un-Protected Areas.

Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

PubMed Central

Eleftherianos, Ioannis; Castillo, Julio Cesar

2012-01-01

Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

A novel computational approach for simultaneous tracking and feature extraction of C. elegans populations in fluid environments.

PubMed

Tsechpenakis, Gabriel; Bianchi, Laura; Metaxas, Dimitris; Driscoll, Monica

2008-05-01

The nematode Caenorhabditis elegans (C. elegans) is a genetic model widely used to dissect conserved basic biological mechanisms of development and nervous system function. C. elegans locomotion is under complex neuronal regulation and is impacted by genetic and environmental factors; thus, its analysis is expected to shed light on how genetic, environmental, and pathophysiological processes control behavior. To date, computer-based approaches have been used for analysis of C. elegans locomotion; however, none of these is both high resolution and high throughput. We used computer vision methods to develop a novel automated approach for analyzing the C. elegans locomotion. Our method provides information on the position, trajectory, and body shape during locomotion and is designed to efficiently track multiple animals (C. elegans) in cluttered images and under lighting variations. We used this method to describe in detail C. elegans movement in liquid for the first time and to analyze six unc-8, one mec-4, and one odr-1 mutants. We report features of nematode swimming not previously noted and show that our method detects differences in the swimming profile of mutants that appear at first glance similar.

A variant of nested dissection for solving n by n grid problems

NASA Technical Reports Server (NTRS)

George, A.; Poole, W. G., Jr.; Voigt, R. G.

1976-01-01

Nested dissection orderings are known to be very effective for solving the sparse positive definite linear systems which arise from n by n grid problems. In this paper nested dissection is shown to be the final step of incomplete nested dissection, an ordering which corresponds to the premature termination of dissection. Analyses of the arithmetic and storage requirements for incomplete nested dissection are given, and the ordering is shown to be competitive with nested dissection under certain conditions.

Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

NASA Technical Reports Server (NTRS)

Norga, Koenraad K.; Gurganus, Marjorie C.; Dilda, Christy L.; Yamamoto, Akihiko; Lyman, Richard F.; Patel, Prajal H.; Rubin, Gerald M.; Hoskins, Roger A.; Mackay, Trudy F.; Bellen, Hugo J.

2003-01-01

BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

Mapping Cellular Polarity Networks Using Mass Spectrometry-based Strategies.

PubMed

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

2018-05-18

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

Ecosystems Biology Approaches To Determine Key Fitness Traits of Soil Microorganisms

NASA Astrophysics Data System (ADS)

Brodie, E.; Zhalnina, K.; Karaoz, U.; Cho, H.; Nuccio, E. E.; Shi, S.; Lipton, M. S.; Zhou, J.; Pett-Ridge, J.; Northen, T.; Firestone, M.

2014-12-01

The application of theoretical approaches such as trait-based modeling represent powerful tools to explain and perhaps predict complex patterns in microbial distribution and function across environmental gradients in space and time. These models are mostly deterministic and where available are built upon a detailed understanding of microbial physiology and response to environmental factors. However as most soil microorganisms have not been cultivated, for the majority our understanding is limited to insights from environmental 'omic information. Information gleaned from 'omic studies of complex systems should be regarded as providing hypotheses, and these hypotheses should be tested under controlled laboratory conditions if they are to be propagated into deterministic models. In a semi-arid Mediterranean grassland system we are attempting to dissect microbial communities into functional guilds with defined physiological traits and are using a range of 'omics approaches to characterize their metabolic potential and niche preference. Initially, two physiologically relevant time points (peak plant activity and prior to wet-up) were sampled and metagenomes sequenced deeply (600-900 Gbp). Following assembly, differential coverage and nucleotide frequency binning were carried out to yield draft genomes. In addition, using a range of cultivation media we have isolated a broad range of bacteria representing abundant bacterial genotypes and with genome sequences of almost 40 isolates are testing genomic predictions regarding growth rate, temperature and substrate utilization in vitro. This presentation will discuss the opportunities and challenges in parameterizing microbial functional guilds from environmental 'omic information for use in trait-based models.

Regeneration in the era of functional genomics and gene network analysis.

PubMed

Smith, Joel; Morgan, Jennifer R; Zottoli, Steven J; Smith, Peter J; Buxbaum, Joseph D; Bloom, Ona E

2011-08-01

What gives an organism the ability to regrow tissues and to recover function where another organism fails is the central problem of regenerative biology. The challenge is to describe the mechanisms of regeneration at the molecular level, delivering detailed insights into the many components that are cross-regulated. In other words, a broad, yet deep dissection of the system-wide network of molecular interactions is needed. Functional genomics has been used to elucidate gene regulatory networks (GRNs) in developing tissues, which, like regeneration, are complex systems. Therefore, we reason that the GRN approach, aided by next generation technologies, can also be applied to study the molecular mechanisms underlying the complex functions of regeneration. We ask what characteristics a model system must have to support a GRN analysis. Our discussion focuses on regeneration in the central nervous system, where loss of function has particularly devastating consequences for an organism. We examine a cohort of cells conserved across all vertebrates, the reticulospinal (RS) neurons, which lend themselves well to experimental manipulations. In the lamprey, a jawless vertebrate, there are giant RS neurons whose large size and ability to regenerate make them particularly suited for a GRN analysis. Adding to their value, a distinct subset of lamprey RS neurons reproducibly fail to regenerate, presenting an opportunity for side-by-side comparison of gene networks that promote or inhibit regeneration. Thus, determining the GRN for regeneration in RS neurons will provide a mechanistic understanding of the fundamental cues that lead to success or failure to regenerate.

Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

PubMed Central

Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

2012-01-01

Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

Application of three-dimensional rendering in joint-related ganglion cysts.

PubMed

Spinner, Robert J; Edwards, Phillip K; Amrami, Kimberly K

2006-05-01

The origin of para-articular cysts is poorly understood and controversial. The relatively common, simple (extraneural) cysts are presumed to be derived from joints, although joint connections are not always established. Rarer complex cysts are thought by many to form de novo within nerves (intraneural ganglion cysts) or within vessels (adventitial cysts) (degenerative theory). We believe that these simple and complex ganglion cysts are joint-related (articular theory). Joint connections are often not readily appreciated with routine imaging or at surgery. Not identifying and/or treating joint connections frequently leads to cyst recurrence. More sophisticated imaging may enhance visualization of these joint connections. We created a 3D rendering technique to assess potential joint connections of simple and complex cysts localized to the knee and superior tibiofibular joints in patients with fibular (peroneal) neuropathy. Two- and three-dimensional data sets from MRI examinations were segmented semiautomatically by signal intensity with further refinement based on interaction with the user to identify specific anatomic structures, such as small nerves and vessels on serial images. The bone, cysts, nerves, and vessels were each assigned different color representations, and 3D renderings were created in ANALYZE using the data sets closest to isotropic (voxel with equal length in all dimensions) resolution as the primary background rendering. We selected four cases to illustrate the spectrum of pathology. In all of these cases, we demonstrated joint connections and correlated imaging and operative findings. Surgery addressing the cyst and the joint connection resulted in excellent outcomes; postoperative MRIs done more than 6 months later confirmed that there was no recurrence. In addition to highlighting the important relationship of these cysts to neighboring anatomic structures, this 3D technique allows visualization of "occult" connections not readily appreciated with standard MR imaging. We believe that these joint-related cysts have a common pathogenesis; they dissect through a capsular rent and follow the path of least resistance; they may form simple cysts by dissecting out into the soft tissue, or more complex cysts by dissecting within the epineurium of nerves or adventitia of vessels (along an articular branch), or various combinations of all of these types of cysts. Understanding the pathogenesis for cyst formation will improve surgical management and outcomes. We have adapted this 3D technique to enhance the visualization of cysts occurring at other joints.

Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

NASA Technical Reports Server (NTRS)

Fritzsch, B.; Beisel, K. W.; Bermingham, N. A.

2000-01-01

This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

Massively Parallel Sequencing Reveals the Complex Structure of an Irradiated Human Chromosome on a Mouse Background in the Tc1 Model of Down Syndrome

PubMed Central

Clayton, Stephen; Prigmore, Elena; Langley, Elizabeth; Yang, Fengtang; Maguire, Sean; Fu, Beiyuan; Rajan, Diana; Sheppard, Olivia; Scott, Carol; Hauser, Heidi; Stephens, Philip J.; Stebbings, Lucy A.; Ng, Bee Ling; Fitzgerald, Tomas; Quail, Michael A.; Banerjee, Ruby; Rothkamm, Kai; Tybulewicz, Victor L. J.; Fisher, Elizabeth M. C.; Carter, Nigel P.

2013-01-01

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439. PMID:23596509

Immune-Complexed Adenovirus Induce AIM2-Mediated Pyroptosis in Human Dendritic Cells

PubMed Central

Eichholz, Karsten; Bru, Thierry; Tran, Thi Thu Phuong; Fernandes, Paulo; Mennechet, Franck J. D.; Manel, Nicolas; Alves, Paula; Perreau, Matthieu

2016-01-01

Human adenoviruses (HAdVs) are nonenveloped proteinaceous particles containing a linear double-stranded DNA genome. HAdVs cause a spectrum of pathologies in all populations regardless of health standards. Following repeat exposure to multiple HAdV types, we develop robust and long-lived humoral and cellular immune responses that provide life-long protection from de novo infections and persistent HAdV. How HAdVs, anti-HAdV antibodies and antigen presenting cells (APCs) interact to influence infection is still incompletely understood. In our study, we used physical, pharmacological, biochemical, fluorescence and electron microscopy, molecular and cell biology approaches to dissect the impact of immune-complexed HAdV (IC-HAdV) on human monocyte-derived dendritic cells (MoDCs). We show that IC-HAdV generate stabilized complexes of ~200 nm that are efficiently internalized by, and aggregate in, MoDCs. By comparing IC-HAdV, IC-empty capsid, IC-Ad2ts1 (a HAdV-C2 impaired in endosomal escape due to a mutation that impacts protease encapsidation) and IC-AdL40Q (a HAdV-C5 impaired in endosomal escape due to a mutation in protein VI), we demonstrate that protein VI-dependent endosomal escape is required for the HAdV genome to engage the DNA pattern recognition receptor AIM2 (absent in melanoma 2). AIM2 engagement induces pyroptotic MoDC death via ASC (apoptosis-associated speck protein containing a caspase activation/recruitment domain) aggregation, inflammasome formation, caspase 1 activation, and IL-1β and gasdermin D (GSDMD) cleavage. Our study provides mechanistic insight into how humoral immunity initiates an innate immune response to HAdV-C5 in human professional APCs. PMID:27636895

Anatomical bases of the surgical dissection of the interatrial septum: a morphological and histological study.

PubMed

Filaire, Marc; Nohra, Olivier; Sakka, Laurent; Chadeyras, Jean Baptiste; Da Costa, Valence; Naamee, Adel; Bailly, Patrick; Escande, Georges

2008-06-01

The interatrial septum (IAS) can be dissected to resect pulmonary tumors invading the left atrium. The aim of this study was to describe the dissected structures, and to expose the benefits, the limits, and the embryologic reasons of such dissection. We dissected the IAS of 11 fresh, non-embalmed human hearts. The dissected structures were described and the length and depth of the dissection were measured. A histological study was performed in four other fresh hearts to identify and differentiate between dissectible and non-dissectible structures. The dissection was performed through a fatty tissue located between two muscular walls. The depth limit of the IAS dissection was identified as the limbus of the fossa ovalis and the muscular roof of the atria. The section of the latter doubles the depth of the dissection at the level of the upper pulmonary veins. Mean length of the dissected IAS was 77 mm (55-90). Mean depths of the IAS were 41 mm (35-50) at the level of the left upper pulmonary vein, 27 mm (12-35) between the upper and lower pulmonary veins, and 14 mm (8-20) at the level of the left inferior pulmonary vein The surgical dissection of the IAS is performed through the septum secundum that appears as an infold of the atrial wall. The length of the resectable left atrial cuff reaches a mean of 40 mm at the level of the upper pulmonary vein.

Assessment of stent edge dissections by fractional flow reserve.

PubMed

Chung, Ju-Hyun; Ann, Soe Hee; Koo, Bon-Kwon; Nam, Chang-Wook; Doh, Joon-Hyung; Singh, Gillian Balbir; Kim, Hyung Il; Shin, Eun-Seok

2015-04-15

Edge dissections after intervention have been studied with imaging techniques, however, functional assessment has not been studied yet. We investigated the relationship between fractional flow reserve (FFR) and the angiographic type of stent edge dissections and tried to assess the use of FFR-guided management for edge dissection. 51 edge dissections assessed by FFR were included in this prospective observational study. FFR was measured for each type of edge dissection and compared with quantitative coronary angiographic findings. Clinical outcomes were evaluated based on FFR measurements. Edge dissections were classified as type A (47.1%; 24/51), type B (41.2%; 21/51), type C (2.0%; 1/51) and type D (9.8%; 5/51). Mean FFR in type A dissection was 0.87 ± 0.09, in type B 0.86 ± 0.07, in type C 0.72 and in type D 0.57 ± 0.08. All type C and D dissections (6/51) had FFR ≤ 0.8 and were treated with additional stents. Among the 45 type A and B dissections, 8 had a FFR ≤ 0.8 (17.8%), and 50% received additional stenting. All dissections with FFR >0.8 were left untreated except one long dissection case. There was no death, myocardial infarction or target lesion revascularization during hospitalization or the follow-up period (median 152 days; IQR 42-352 days). FFR correlates well with an angiographic type of edge dissection. Angiographic findings are sufficient for deciding the treatment of severe dissections such as types C and D, while FFR-guided management may be safe and effective for mild edge dissections such as types A and B. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dissecting Situational Strength: Theoretical Analysis and Empirical Tests

DTIC Science & Technology

2012-09-01

behavior , and to the complexity of personality and its multiple and interacting determinants ” (Mischel, 1999; p. 456; see also Mischel, 1968). Mischel...outcome relationships. Specifically, he posited that traits have less of a determining impact on behaviors in “strong” situations, which provide: (1...which situations interact with personality in determining voluntary work behavior (Project One) and the extent to which people respond adversely to

Genetic, Genomic, and Breeding Approaches to Further Explore Kernel Composition Traits and Grain Yield in Maize

ERIC Educational Resources Information Center

Da Silva, Helena Sofia Pereira

2009-01-01

Maize ("Zea mays L.") is a model species well suited for the dissection of complex traits which are often of commercial value. The purpose of this research was to gain a deeper understanding of the genetic control of maize kernel composition traits starch, protein, and oil concentration, and also kernel weight and grain yield. Germplasm with…

Anatomy of the sural nerve: cadaver study and literature review.

PubMed

Riedl, Otto; Frey, Manfred

2013-04-01

The sural nerve is commonly used as donor for nerve grafting. Contrary to its constant retromalleolar position, formation and course of the proximal sural nerve show great variability. The coexistence of different and deceptive terminologies contributes to the complexity, and reviewing the international literature is confusing. Because detailed anatomical knowledge is essential for efficient and safe sural nerve harvesting, this study aims to bring clarity. Previous sural nerve reports listed in the PubMed database and established anatomical textbooks were reviewed. Different terminologies were compared and adjusted. Anatomical details and variations were noted. Subtle prospective anatomical dissections and comparison with actual data followed. Two hundred twenty-one relevant reports were identified and worked up going back to the nineteenth century. Fourteen established German and English language anatomical textbooks were reviewed. Thirty lower limbs were dissected. In total, this study pools the information of more than 2500 sural nerves. This study covers all information about the sural nerve anatomy published internationally. The coexistence of different and confusing terminologies is pinpointed and adjusted to allow comparison of previous reports and to gain a coordinated data pool of more than 2500 investigated sural nerves. Detailed features are clearly described and summarized, findings from the authors' own prospective dissections complete these data, and the prior existing anatomical confusion is resolved. Finally, clinical implications are described.

Comparison of five systems for staging lymph node metastasis in gastric cancer.

PubMed

Yu, W; Choi, G S; Whang, I; Suh, I S

1997-09-01

There are several systems for staging lymph node metastasis in gastric cancer. Their relative merits are not clear. In this retrospective analysis, the nodal status was classified according to the Union Internacional Contra la Cancrum (UICC) and Japanese staging systems, the number and frequency of lymph node metastasis, and the level of involved nodes. Each staging system was scored as good (+1), fair (0) or poor (-1) with respect to prognostic value, theoretical value, convenience, reproducibility and surgical applicability. There were no differences between the five staging systems in predicting survival. The Japanese staging system was most arbitrary owing to the complexity of the system, although it had an advantage in surgical application. The same disadvantage was found in the UICC system and the level system. Determination of the number and frequency of involved nodes was convenient and reproducible, but the number of lymph nodes dissected must be considered when the number of positive nodes is used for staging. The classification of metastasis to the regional lymph nodes as N0 (no nodal metastasis), N1 (metastasis in 1-25 per cent of dissected nodes) and N2 (metastasis in more than 25 per cent of dissected nodes) would be a simple, convenient, reproducible staging system with an ability to predict surgical results.

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles

PubMed Central

Li, Ruohan; Harvey, Alan R.; Hodgetts, Stuart I.

2017-01-01

Large numbers of long noncoding RNAs have been discovered in recent years, but only a few have been characterized. NEAT1 (nuclear paraspeckle assembly transcript 1) is a mammalian long noncoding RNA that is important for the reproductive physiology of mice, cancer development, and the formation of subnuclear bodies termed paraspeckles. The two major isoforms of NEAT1 (3.7 kb NEAT1_1 and 23 kb NEAT1_2 in human) are generated from a common promoter and are produced through the use of alternative transcription termination sites. This gene structure has made the functional relationship between the two isoforms difficult to dissect. Here we used CRISPR-Cas9 genome editing to create several different cell lines: total NEAT1 knockout cells, cells that only express the short form NEAT1_1, and cells with twofold more NEAT1_2. Using these reagents, we obtained evidence that NEAT1_1 is not a major component of paraspeckles. In addition, our data suggest NEAT1_1 localizes in numerous nonparaspeckle foci we termed “microspeckles,” which may carry paraspeckle-independent functions. This study highlights the complexity of lncRNA and showcases how genome editing tools are useful in dissecting the structural and functional roles of overlapping transcripts. PMID:28325845

[Genetic dissection of intracranial aneurysm].

PubMed

Onda, Hideaki; Yoneyama, Taku; Akagawa, Hiroyuki; Kasuya, Hidetoshi

2008-11-01

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm (IA) is a devastating condition with high mortality and morbidity. Genetic as well as environment factors play important roles in the pathogenesis of SAH and IAs. We review the present knowledge on the genetic factors responsible for SAH or IAs. Linkage analysis and association study are used for genetic dissection. Genome-wide linkage analyses have specified several genetic loci for IAs and 6 loci (1p34-36, 7q11, 11q24-25, 14q22-31, 19q13, and Xp22) have been replicated in different populations. Numerous functional and/or positional candidate genes for IAs have been investigated by case-control association studies. The results of genetic association studies are modest because of small sample sizes. To date, no specific genes have been identified as responsible for IA development or rupture. Recent, large-scale genome-wide association (GWA) studies have revealed consistent and replicable genetic markers of several complex diseases such as coronary artery disease and type 2 diabetes. Although, thus far, no GWA studies have been performed for IAs, such a study may accomplish the breakthrough of genetic dissection of IAs. The identification of susceptible genes might lead to the understanding of the mechanism of IA formation or rupture and to novel therapeutic strategies.

Modern chromatographic and mass spectrometric techniques for protein biopharmaceutical characterization.

PubMed

Sandra, Koen; Vandenheede, Isabel; Sandra, Pat

2014-03-28

Protein biopharmaceuticals such as monoclonal antibodies and therapeutic proteins are currently in widespread use for the treatment of various life-threatening diseases including cancer, autoimmune disorders, diabetes and anemia. The complexity of protein therapeutics is far exceeding that of small molecule drugs; hence, unraveling this complexity represents an analytical challenge. The current review provides the reader with state-of-the-art chromatographic and mass spectrometric tools available to dissect primary and higher order structures, post-translational modifications, purity and impurity profiles and pharmacokinetic properties of protein therapeutics. Copyright © 2013 Elsevier B.V. All rights reserved.

Native gel analysis for RISC assembly.

PubMed

Kawamata, Tomoko; Tomari, Yukihide

2011-01-01

Small-interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate expression of their target mRNAs via the RNA-induced silencing complex (RISC). A core component of RISC is the Argonaute (Ago) protein, which dictates the RISC function. In Drosophila, miRNAs and siRNAs are generally loaded into Ago1-containing RISC (Ago1-RISC) and Ago2-containing RISC (Ago2-RISC), respectively. We developed a native agarose gel system to directly detect Ago1-RISC, Ago2-RISC, and their precursor complexes. Methods presented here will provide powerful tools to biochemically dissect the RISC assembly pathways.

Endovascular treatment of patients with types A and B thoracic aortic dissection using Relay thoracic stent-grafts: results from the RESTORE Patient Registry.

PubMed

Zipfel, Burkhart; Czerny, Martin; Funovics, Martin; Coppi, Gioacchino; Ferro, Carlo; Rousseau, Hervé; Berti, Sergio; Tealdi, Domenico G; Riambau, Vincent; Mangialardi, Nicola; Sassi, Carlo

2011-04-01

To evaluate the safety and performance of Relay stent-grafts in patients with acute or chronic aortic dissections. Patients with types A or B aortic dissections suitable for treatment with Relay stent-grafts and followed for 2 years after thoracic endovascular aortic repair (TEVAR) were identified from a company-sponsored registry database established in January 2006. Ninety-one consecutive patients (69 men; mean age 65 years) underwent TEVAR with Relay stent-grafts for dissection. Most patients (76, 84%) had type B dissections; 61 of all patients were classified as chronic and 30 as acute. The technical success rate was 95% (97% in acute, 95% in chronic, and 93% in type B dissections). The type I endoleak rate was 7% (7% in acute and 8% in chronic dissections); all occurred in patients with type B dissections. Paraplegia, paraparesis, and stroke occurred in 4, 1, and 2 patients, respectively; 2 cases of paraplegia occurred in patients with acute type B dissections. Thirty-day mortality was 8% (13% in acute and 5% in chronic dissections); all deaths occurred in patients with type B dissections. The 2-year survival rate was 82% in the overall population and 84% in patients with type B dissections. The combination of Relay's features, such as stent conformability, radial force, atraumatic design, and controlled deployment and fixation, may contribute to the safety of the Relay stent-grafts for the treatment of thoracic aortic dissections, including acute and chronic type B dissections.

Pain, quality of life, and spinal accessory nerve status after neck dissection.

PubMed

Terrell, J E; Welsh, D E; Bradford, C R; Chepeha, D B; Esclamado, R M; Hogikyan, N D; Wolf, G T

2000-04-01

To assess quality of life (QOL) in patients with head and neck cancer who underwent neck dissection and to compare QOL scores for patients in whom the spinal accessory nerve (CN XI) was resected or preserved. SETTING AND DESIGN AND OUTCOMES MEASURES: Three hundred ninety-seven patients who had undergone treatment for head and neck cancer completed the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Study SF-12 General Health Survey, and questions on "pain despite pain medications" and headaches. Of the 397 patients, 222 had no neck dissection, 46 had neck dissections resecting CN XI, and 129 had dissection sparing CN XI. Of the latter group, 68 patients had dissections sparing level V and 61 dissections included level V. Age, sex, primary site distribution, and T stage were not different between the groups. Patients who had neck dissections sparing CN XI had better scores on the HNQOL pain domain (P = .002), had less shoulder or neck pain (P = .003), and took pain medications less frequently (P = .0004) compared with patients who had neck dissections sacrificing CN XI. When CN XI was preserved, patients who had no level V dissection had better pain domain scores (P = .03) and eating domain scores (P = .007) on the HNQOL, had less shoulder or neck pain (P = .006), and had less physical problems (P = .03) than patients who had level V dissected. On multivariate analysis, pain-related QOL scores after neck dissection were significantly better (P < .01) if patients had dissections with preservation of CN XI and if level V was not dissected. Neck dissections sparing CN XI are associated with better pain scores on the HNQOL, less shoulder and neck pain, and less need for medications. When CN XI is spared, not dissecting level V of the neck is associated with better HNQOL pain scores, less shoulder or neck pain, and fewer physical problems.

A data management approach to quality assurance using colorectal carcinoma reports from two institutions as a model.

PubMed

Sorge, John P; Harmon, C Reid; Sherman, Susan M; Baillie, E Eugene

2005-07-01

We used data management software to compare pathology report data concerning regional lymph node sampling for colorectal carcinoma from 2 institutions using different dissection methods. Data were retrieved from 2 disparate anatomic pathology information systems for all cases of colorectal carcinoma in 2003 involving the ascending and descending colon. Initial sorting of the data included overall lymph node recovery to assess differences between the dissection methods at the 2 institutions. Additional segregation of the data was used to challenge the application's capability of accurately addressing the complexity of the process. This software approach can be used to evaluate data from disparate computer systems, and we demonstrate how an automated function can enable institutions to compare internal pathologic assessment processes and the results of those comparisons. The use of this process has future implications for pathology quality assurance in other areas.

A ‘tool box’ for deciphering neuronal circuits in the developing chick spinal cord

PubMed Central

Hadas, Yoav; Etlin, Alex; Falk, Haya; Avraham, Oshri; Kobiler, Oren; Panet, Amos; Lev-Tov, Aharon; Klar, Avihu

2014-01-01

The genetic dissection of spinal circuits is an essential new means for understanding the neural basis of mammalian behavior. Molecular targeting of specific neuronal populations, a key instrument in the genetic dissection of neuronal circuits in the mouse model, is a complex and time-demanding process. Here we present a circuit-deciphering ‘tool box’ for fast, reliable and cheap genetic targeting of neuronal circuits in the developing spinal cord of the chick. We demonstrate targeting of motoneurons and spinal interneurons, mapping of axonal trajectories and synaptic targeting in both single and populations of spinal interneurons, and viral vector-mediated labeling of pre-motoneurons. We also demonstrate fluorescent imaging of the activity pattern of defined spinal neurons during rhythmic motor behavior, and assess the role of channel rhodopsin-targeted population of interneurons in rhythmic behavior using specific photoactivation. PMID:25147209

The study of anatomy in England from 1700 to the early 20th century

PubMed Central

Mitchell, Piers D; Boston, Ceridwen; Chamberlain, Andrew T; Chaplin, Simon; Chauhan, Vin; Evans, Jonathan; Fowler, Louise; Powers, Natasha; Walker, Don; Webb, Helen; Witkin, Annsofie

2011-01-01

The study of anatomy in England during the 18th and 19th century has become infamous for bodysnatching from graveyards to provide a sufficient supply of cadavers. However, recent discoveries have improved our understanding of how and why anatomy was studied during the enlightenment, and allow us to see the context in which dissection of the human body took place. Excavations of infirmary burial grounds and medical school cemeteries, study of hospital archives, and analysis of the content of surviving anatomical collections in medical museums enables us to re-evaluate the field from a fresh perspective. The pathway from a death in poverty, sale of the corpse to body dealer, dissection by anatomist or medical student, and either the disposal and burial of the remains or preservation of teaching specimens that survive today in medical museums is a complex and fascinating one. PMID:21496014

A Drosophila Toolkit for the Visualization and Quantification of Viral Replication Launched from Transgenic Genomes

PubMed Central

Wernet, Mathias F.; Klovstad, Martha; Clandinin, Thomas R.

2014-01-01

Arthropod RNA viruses pose a serious threat to human health, yet many aspects of their replication cycle remain incompletely understood. Here we describe a versatile Drosophila toolkit of transgenic, self-replicating genomes (‘replicons’) from Sindbis virus that allow rapid visualization and quantification of viral replication in vivo. We generated replicons expressing Luciferase for the quantification of viral replication, serving as useful new tools for large-scale genetic screens for identifying cellular pathways that influence viral replication. We also present a new binary system in which replication-deficient viral genomes can be activated ‘in trans’, through co-expression of an intact replicon contributing an RNA-dependent RNA polymerase. The utility of this toolkit for studying virus biology is demonstrated by the observation of stochastic exclusion between replicons expressing different fluorescent proteins, when co-expressed under control of the same cellular promoter. This process is analogous to ‘superinfection exclusion’ between virus particles in cell culture, a process that is incompletely understood. We show that viral polymerases strongly prefer to replicate the genome that encoded them, and that almost invariably only a single virus genome is stochastically chosen for replication in each cell. Our in vivo system now makes this process amenable to detailed genetic dissection. Thus, this toolkit allows the cell-type specific, quantitative study of viral replication in a genetic model organism, opening new avenues for molecular, genetic and pharmacological dissection of virus biology and tool development. PMID:25386852

Coordination of cellular differentiation, polarity, mitosis and meiosis - New findings from early vertebrate oogenesis.

PubMed

Elkouby, Yaniv M; Mullins, Mary C

2017-10-15

A mechanistic dissection of early oocyte differentiation in vertebrates is key to advancing our knowledge of germline development, reproductive biology, the regulation of meiosis, and all of their associated disorders. Recent advances in the field include breakthroughs in the identification of germline stem cells in Medaka, in the cellular architecture of the germline cyst in mice, in a mechanistic dissection of chromosomal pairing and bouquet formation in meiosis in mice, in tracing oocyte symmetry breaking to the chromosomal bouquet of meiosis in zebrafish, and in the biology of the Balbiani body, a universal oocyte granule. Many of the major events in early oogenesis are universally conserved, and some are co-opted for species-specific needs. The chromosomal events of meiosis are of tremendous consequence to gamete formation and have been extensively studied. New light is now being shed on other aspects of early oocyte differentiation, which were traditionally considered outside the scope of meiosis, and their coordination with meiotic events. The emerging theme is of meiosis as a common groundwork for coordinating multifaceted processes of oocyte differentiation. In an accompanying manuscript we describe methods that allowed for investigations in the zebrafish ovary to contribute to these breakthroughs. Here, we review these advances mostly from the zebrafish and mouse. We discuss oogenesis concepts across established model organisms, and construct an inclusive paradigm for early oocyte differentiation in vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Neck dissection

MedlinePlus

... cancer - neck dissection; Throat cancer - neck dissection; Squamous cell cancer - neck dissection ... blood cells around the body to fight infection. Cancer cells in the mouth or throat can travel in ...

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

PubMed

Louridas, George E; Lourida, Katerina G

2017-02-21

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

A minimally invasive technique for percutaneous lumbar facet augmentation: Technical description of a novel device

PubMed Central

Smith, Zachary A.; Armin, Sean; Raphael, Dan; Khoo, Larry T.

2011-01-01

Background: We describe a new posterior dynamic stabilizing system that can be used to augment the mechanics of the degenerating lumbar segment. The mechanism of this system differs from other previously described surgical techniques that have been designed to augment lumbar biomechanics. The implant and technique we describe is an extension-limiting one, and it is designed to support and cushion the facet complex. Furthermore, it is inserted through an entirely percutaneous technique. The purpose of this technical note is to demonstrate a novel posterior surgical approach for the treatment of lumbar degenerative. Methods: This report describes a novel, percutaneously placed, posterior dynamic stabilization system as an alternative option to treat lumbar degenerative disk disease with and without lumbar spinal stenosis. The system does not require a midline soft-tissue dissection, nor subperiosteal dissection, and is a truly minimally invasive means for posterior augmentation of the functional facet complex. This system can be implanted as a stand-alone procedure or in conjunction with decompression procedures. Results: One-year clinical results in nine individual patients, all treated for degenerative disease of the lower lumbar spine, are presented. Conclusions: This novel technique allows for percutaneous posterior dynamic stabilization of the lumbar facet complex. The use of this procedure may allow a less invasive alternative to traditional approaches to the lumbar spine as well as an alternative to other newly developed posterior dynamic stabilization systems. PMID:22145084

Mammalian Exo1 encodes both structural and catalytic functions that play distinct roles in essential biological processes

PubMed Central

Schaetzlein, Sonja; Chahwan, Richard; Avdievich, Elena; Roa, Sergio; Wei, Kaichun; Eoff, Robert L.; Sellers, Rani S.; Clark, Alan B.; Kunkel, Thomas A.; Scharff, Matthew D.; Edelmann, Winfried

2013-01-01

Mammalian Exonuclease 1 (EXO1) is an evolutionarily conserved, multifunctional exonuclease involved in DNA damage repair, replication, immunoglobulin diversity, meiosis, and telomere maintenance. It has been assumed that EXO1 participates in these processes primarily through its exonuclease activity, but recent studies also suggest that EXO1 has a structural function in the assembly of higher-order protein complexes. To dissect the enzymatic and nonenzymatic roles of EXO1 in the different biological processes in vivo, we generated an EXO1-E109K knockin (Exo1EK) mouse expressing a stable exonuclease-deficient protein and, for comparison, a fully EXO1-deficient (Exo1null) mouse. In contrast to Exo1null/null mice, Exo1EK/EK mice retained mismatch repair activity and displayed normal class switch recombination and meiosis. However, both Exo1-mutant lines showed defects in DNA damage response including DNA double-strand break repair (DSBR) through DNA end resection, chromosomal stability, and tumor suppression, indicating that the enzymatic function is required for those processes. On a transformation-related protein 53 (Trp53)-null background, the DSBR defect caused by the E109K mutation altered the tumor spectrum but did not affect the overall survival as compared with p53-Exo1null mice, whose defects in both DSBR and mismatch repair also compromised survival. The separation of these functions demonstrates the differential requirement for the structural function and nuclease activity of mammalian EXO1 in distinct DNA repair processes and tumorigenesis in vivo. PMID:23754438

Cardiac Autonomic Regulation in Autism and Fragile X Syndrome: A Review

PubMed Central

Klusek, Jessica; Roberts, Jane E.; Losh, Molly

2014-01-01

Despite the significance of efforts to understand the biological basis of autism, progress in this area has been hindered, in part, by the considerable heterogeneity in the disorder. Fragile X syndrome (FXS), a monogenic condition associated with high risk for autism, may pave the way for the dissection of biological heterogeneity within idiopathic autism. This paper adopts a cross-syndrome biomarker approach to evaluate potentially overlapping profiles of cardiac arousal dysregulation (and broader autonomic dysfunction) in autism and FXS. Approaches such as this, aimed at delineating shared mechanisms across genetic syndromes, hold great potential for improving diagnostic precision, promoting earlier identification, and uncovering key systems that can be targeted in pharmaceutical/behavioral interventions. Biomarker approaches may be vital to deconstructing complex psychiatric disorders, and are currently promoted as such by major research initiatives such as the NIMH Research Domain Criteria (RDoC). Evidence reviewed here supports physiological dysregulation in a subset of individuals with autism, as evidenced by patterns of hyperarousal and dampened parasympathetic vagal tone, which overlap with the well-documented physiological profile of FXS. Moreover, there is growing support for a link between aberrant cardiac activity and core deficits associated with autism, such as communication and social impairment. The delineation of physiological mechanisms common to autism and FXS could lend insight into relationships between genetic etiology and behavioral endstates, highlighting FMR1 as a potential candidate gene. Research gaps and potential pitfalls are discussed to inform timely, well-controlled biomarker research that will ultimately promote better diagnosis and treatment of autism and associated conditions. PMID:25420222

MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.

PubMed

Lawless, Nathan; Reinhardt, Timothy A; Bryan, Kenneth; Baker, Mike; Pesch, Bruce; Zimmerman, Duane; Zuelke, Kurt; Sonstegard, Tad; O'Farrelly, Cliona; Lippolis, John D; Lynn, David J

2014-01-27

Bovine mastitis is an inflammation-driven disease of the bovine mammary gland that costs the global dairy industry several billion dollars per year. Because disease susceptibility is a multifactorial complex phenotype, an integrative biology approach is required to dissect the molecular networks involved. Here, we report such an approach using next-generation sequencing combined with advanced network and pathway biology methods to simultaneously profile mRNA and miRNA expression at multiple time points (0, 12, 24, 36 and 48 hr) in milk and blood FACS-isolated CD14(+) monocytes from animals infected in vivo with Streptococcus uberis. More than 3700 differentially expressed (DE) genes were identified in milk-isolated monocytes (MIMs), a key immune cell recruited to the site of infection during mastitis. Upregulated genes were significantly enriched for inflammatory pathways, whereas downregulated genes were enriched for nonglycolytic metabolic pathways. Monocyte transcriptional changes in the blood, however, were more subtle but highlighted the impact of this infection systemically. Genes upregulated in blood-isolated monocytes (BIMs) showed a significant association with interferon and chemokine signaling. Furthermore, 26 miRNAs were DE in MIMs and three were DE in BIMs. Pathway analysis revealed that predicted targets of downregulated miRNAs were highly enriched for roles in innate immunity (FDR < 3.4E-8), particularly TLR signaling, whereas upregulated miRNAs preferentially targeted genes involved in metabolism. We conclude that during S. uberis infection miRNAs are key amplifiers of monocyte inflammatory response networks and repressors of several metabolic pathways. Copyright © 2014 Lawless et al.

How to Design a Genetic Mating Scheme: A Basic Training Package for Drosophila Genetics

PubMed Central

Roote, John; Prokop, Andreas

2013-01-01

Drosophila melanogaster is a powerful model organism for biological research. The essential and common instrument of fly research is genetics, the art of applying Mendelian rules in the specific context of Drosophila with its unique classical genetic tools and the breadth of modern genetic tools and strategies brought in by molecular biology, transgenic technologies and the use of recombinases. Training newcomers to fly genetics is a complex and time-consuming task but too important to be left to chance. Surprisingly, suitable training resources for beginners currently are not available. Here we provide a training package for basic Drosophila genetics, designed to ensure that basic knowledge on all key areas is covered while reducing the time invested by trainers. First, a manual introduces to fly history, rationale for mating schemes, fly handling, Mendelian rules in fly, markers and balancers, mating scheme design, and transgenic technologies. Its self-study is followed by a practical training session on gender and marker selection, introducing real flies under the dissecting microscope. Next, through self-study of a PowerPoint presentation, trainees are guided step-by-step through a mating scheme. Finally, to consolidate knowledge, trainees are asked to design similar mating schemes reflecting routine tasks in a fly laboratory. This exercise requires individual feedback but also provides unique opportunities for trainers to spot weaknesses and strengths of each trainee and take remedial action. This training package is being successfully applied at the Manchester fly facility and may serve as a model for further training resources covering other aspects of fly research. PMID:23390611

Development and validation of the neck dissection impairment index: a quality of life measure.

PubMed

Taylor, Rodney J; Chepeha, Judith C; Teknos, Theodoros N; Bradford, Carol R; Sharma, Pramod K; Terrell, Jeffrey E; Hogikyan, Norman D; Wolf, Gregory T; Chepeha, Douglas B

2002-01-01

To validate a health-related quality-of-life (QOL) instrument for patients following neck dissection and to identify the factors that affect QOL following neck dissection. Cross-sectional validation study. The outpatient clinic of a tertiary care cancer center. Convenience sample of 54 patients previously treated for head and neck cancer who underwent a selective neck dissection or modified radical neck dissection (64 total neck dissections). Patients had a minimum postoperative convalescence of 11 months. Thirty-two underwent accessory nerve-sparing modified radical neck dissection, and 32 underwent selective neck dissection. A 10-item, self-report instrument, the Neck Dissection Impairment Index (NDII), was developed and validated. Reliability was evaluated with test-retest correlation and internal consistency using the Cronbach alpha coefficient. Convergent validity was assessed using the 36-Item Short-Form Health Survey (SF-36) and the Constant Shoulder Scale, a shoulder function test. Multiple variable regression was used to determine variables that most affected QOL following neck dissection The 10-item NDII test-retest correlation was 0.91 (P<.001) with an internal consistency Cronbach alpha coefficient of.95. The NDII correlated with the Constant Shoulder Scale (r = 0.85, P<.001) and with the SF-36 physical functioning (r = 0.50, P<.001) and role-physical functioning (r = 0.60, P<.001) domains. Using multiple variable regression, the variables that contributed most to QOL score were patient's age and weight, radiation treatment, and neck dissection type. The NDII is a valid, reliable instrument for assessing neck dissection impairment. Patient's age, weight, radiation treatment, and neck dissection type were important factors that affect QOL following neck dissection.

Precancer Atlas to Drive Precision Prevention Trials

DOE PAGES

Spira, Avrum; Yurgelun, Matthew B.; Alexandrov, Ludmil B.; ...

2017-04-01

Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. Here, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposismore » (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape. Emerging genetic and pharmacologic (metformin) disruption of mitochondrial (mt) respiration increased autophagy to prevent cancer in a Li-Fraumeni mouse model (biology reproduced in clinical pilot) and revealed profound influences of subtle changes in mt DNA background variation on obesity, aging, and cancer risk. The elaborate communication between the immune system and neoplasia includes an increasingly complex cellular microenvironment and dynamic interactions between host genetics, environmental factors, and microbes in shaping the immune response. Cancer vaccines are in early murine and clinical precancer studies, building on the recent successes of immunotherapy and HPV vaccine immune prevention. Molecular monitoring in Barrett's esophagus to avoid overdiagnosis/treatment highlights an important PCA theme. Next generation sequencing (NGS) discovered age-related clonal hematopoiesis of indeterminate potential (CHIP). Ultra-deep NGS reports over the past year have redefined the premalignant landscape remarkably identifying tiny clones in the blood of up to 95% of women in their 50s, suggesting that potentially premalignant clones are ubiquitous. Similar data from eyelid skin and peritoneal and uterine lavage fluid provide unprecedented opportunities to dissect the earliest phases of stem/progenitor clonal (and microenvironment) evolution/diversity with new single-cell and liquid biopsy technologies. Cancer mutational signatures reflect exogenous or endogenous processes imprinted over time in precursors. In conclusion, accelerating the prevention of cancer will require a large-scale, longitudinal effort, leveraging diverse disciplines (from genetics, biochemistry, and immunology to mathematics, computational biology, and engineering), initiatives, technologies, and models in developing an integrated multi-omics and immunity PCA – an immense national resource to interrogate, target, and intercept events that drive oncogenesis.« less

Precancer Atlas to Drive Precision Prevention Trials

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

Spira, Avrum; Yurgelun, Matthew B.; Alexandrov, Ludmil B.

Cancer development is a complex process driven by inherited and acquired molecular and cellular alterations. Prevention is the holy grail of cancer elimination, but making this a reality will take a fundamental rethinking and deep understanding of premalignant biology. Here, we propose a national concerted effort to create a Precancer Atlas (PCA), integrating multi-omics and immunity – basic tenets of the neoplastic process. The biology of neoplasia caused by germline mutations has led to paradigm-changing precision prevention efforts, including: tumor testing for mismatch repair (MMR) deficiency in Lynch syndrome establishing a new paradigm, combinatorial chemoprevention efficacy in familial adenomatous polyposismore » (FAP), signal of benefit from imaging-based early detection research in high-germline risk for pancreatic neoplasia, elucidating early ontogeny in BRCA1-mutation carriers leading to an international breast cancer prevention trial, and insights into the intricate germline-somatic-immunity interaction landscape. Emerging genetic and pharmacologic (metformin) disruption of mitochondrial (mt) respiration increased autophagy to prevent cancer in a Li-Fraumeni mouse model (biology reproduced in clinical pilot) and revealed profound influences of subtle changes in mt DNA background variation on obesity, aging, and cancer risk. The elaborate communication between the immune system and neoplasia includes an increasingly complex cellular microenvironment and dynamic interactions between host genetics, environmental factors, and microbes in shaping the immune response. Cancer vaccines are in early murine and clinical precancer studies, building on the recent successes of immunotherapy and HPV vaccine immune prevention. Molecular monitoring in Barrett's esophagus to avoid overdiagnosis/treatment highlights an important PCA theme. Next generation sequencing (NGS) discovered age-related clonal hematopoiesis of indeterminate potential (CHIP). Ultra-deep NGS reports over the past year have redefined the premalignant landscape remarkably identifying tiny clones in the blood of up to 95% of women in their 50s, suggesting that potentially premalignant clones are ubiquitous. Similar data from eyelid skin and peritoneal and uterine lavage fluid provide unprecedented opportunities to dissect the earliest phases of stem/progenitor clonal (and microenvironment) evolution/diversity with new single-cell and liquid biopsy technologies. Cancer mutational signatures reflect exogenous or endogenous processes imprinted over time in precursors. In conclusion, accelerating the prevention of cancer will require a large-scale, longitudinal effort, leveraging diverse disciplines (from genetics, biochemistry, and immunology to mathematics, computational biology, and engineering), initiatives, technologies, and models in developing an integrated multi-omics and immunity PCA – an immense national resource to interrogate, target, and intercept events that drive oncogenesis.« less

En Bloc Hilar Dissection of the Right Hepatic Artery in Continuity with the Bile Duct: a Technique to Reduce Biliary Complications After Adult Living-Donor Liver Transplantation.

PubMed

Abu-Gazala, Samir; Olthoff, Kim M; Goldberg, David S; Shaked, Abraham; Abt, Peter L

2016-04-01

Techniques that preserve the right hepatic artery and the common bile duct in continuity during the dissection may be associated with lower rates of biliary complications in living-donor liver transplants. This study sought to determine whether en bloc hilar dissections were associated with fewer biliary complications in living-donor liver transplants. This was a retrospective review of 41 adult LDLTs performed in a single, liver transplant center between February 2007 and September 2014. The primary outcome of interest was the occurrence of at least one of the following biliary complications: anastomotic leak, stricture, or biloma. The primary predictor of interest was the hilar dissection technique: conventional hilar dissection vs. en bloc hilar dissection. A total of 41 LDLTs were identified, 24 had a conventional, and 17 an en bloc hilar biliary dissection. The occurrence of any biliary complication was significantly more common in the conventional hilar dissection group compared to the en bloc hilar dissection group (66.7 vs. 35.3%, respectively, p = 0.047). In particularly, anastomotic strictures were significantly more common in the conventional hilar dissection group compared to the en bloc hilar dissection group (54.2 vs. 23.5%., respectively, p = 0.049). En bloc hilar dissection technique may decrease biliary complication rates in living donor liver transplants.

Development and application of bond cleavage reactions in bioorthogonal chemistry.

PubMed

Li, Jie; Chen, Peng R

2016-03-01

Bioorthogonal chemical reactions are a thriving area of chemical research in recent years as an unprecedented technique to dissect native biological processes through chemistry-enabled strategies. However, current concepts of bioorthogonal chemistry have largely centered on 'bond formation' reactions between two mutually reactive bioorthogonal handles. Recently, in a reverse strategy, a collection of 'bond cleavage' reactions has emerged with excellent biocompatibility. These reactions have expanded our bioorthogonal chemistry repertoire, enabling an array of exciting new biological applications that range from the chemically controlled spatial and temporal activation of intracellular proteins and small-molecule drugs to the direct manipulation of intact cells under physiological conditions. Here we highlight the development and applications of these bioorthogonal cleavage reactions. Furthermore, we lay out challenges and propose future directions along this appealing avenue of research.

The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

PubMed Central

Guerra, Daniel J.

2011-01-01

Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD. PMID:22937247

Exciting middle and high school students about immunology: an easy, inquiry-based lesson.

PubMed

Lukin, Kara

2013-03-01

High school students in the United States are apathetic about science, technology, engineering and mathematics (STEM), and the workforce pipeline in these areas is collapsing. The lack of understanding of basic principles of biology means that students are unable to make educated decisions concerning their personal health. To address these issues, we have developed a simple, inquiry-based outreach lesson centered on a mouse dissection. Students learn key concepts in immunology and enhance their understanding of human organ systems. The experiment highlights aspects of the scientific method and authentic data collection and analysis. This hands-on activity stimulates interest in biology, personal health and careers in STEM fields. Here, we present all the information necessary to execute the lesson effectively with middle and high school students.

Deconstructing Pancreas Developmental Biology

PubMed Central

Benitez, Cecil M.; Goodyer, William R.

2012-01-01

The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development. PMID:22587935

A Novel Ex Vivo Training Model for Acquiring Supermicrosurgical Skills Using a Chicken Leg.

PubMed

Cifuentes, Ignacio J; Rodriguez, José R; Yañez, Ricardo A; Salisbury, María C; Cuadra, Álvaro J; Varas, Julian E; Dagnino, Bruno L

2016-11-01

Background  Supermicrosurgery is a technique used for dissection and anastomosis of submillimeter diameter vessels. This technique requires precise hand movements and superb eye-hand coordination, making continuous training necessary. Biological in vivo and ex vivo models have been described for this purpose, the latter being more accessible and cost-effective. The aim of this study is to present a new ex vivo training model using a chicken leg. Methods  In 28 chicken legs, an anatomical study was performed. An intramuscular perforator vessel was identified and dissected. Arterial diameters of 0.7, 0.5, and 0.3 mm were identified and consistency of the perforator was assessed. In additional 10 chicken legs, 25 submillimeter arteries were anastomosed using this perforator vessel. Five arteries of 0.3 and 10 of 0.5 mm were anastomosed with nylon 11-0 and 12-0 sutures. Intravascular stent (IVaS) technique and open guide (OG) technique were used in 0.5-mm arteries. A total of 10 arteries of 0.7 mm were anastomosed using 10-0 sutures in a conventional fashion. Dissection and anastomosis time were recorded and patency was tested. Results  We were able to identify 0.7 to 0.3 mm diameter arteries in all the specimens and confirm the consistency of the perforator. The median time for dissection was 13.4 minutes. The median time for anastomosis was 32.3 minutes for 0.3-mm arteries, 24.3 minutes for 0.5-mm arteries using IVaS, 29.5 minutes for the OG technique, and 20.9 minutes for the 0.7 mm diameter arteries. All the anastomoses were permeable. Conclusion  Due to its consistent and adequate diameter vessels, this model is adequate for training supermicrosurgical skills. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Focused Metabolite Profiling for Dissecting Cellular and Molecular Processes of Living Organisms in Space Environments

NASA Technical Reports Server (NTRS)

2008-01-01

Regulatory control in biological systems is exerted at all levels within the central dogma of biology. Metabolites are the end products of all cellular regulatory processes and reflect the ultimate outcome of potential changes suggested by genomics and proteomics caused by an environmental stimulus or genetic modification. Following on the heels of genomics, transcriptomics, and proteomics, metabolomics has become an inevitable part of complete-system biology because none of the lower "-omics" alone provide direct information about how changes in mRNA or protein are coupled to changes in biological function. The challenges are much greater than those encountered in genomics because of the greater number of metabolites and the greater diversity of their chemical structures and properties. To meet these challenges, much developmental work is needed, including (1) methodologies for unbiased extraction of metabolites and subsequent quantification, (2) algorithms for systematic identification of metabolites, (3) expertise and competency in handling a large amount of information (data set), and (4) integration of metabolomics with other "omics" and data mining (implication of the information). This article reviews the project accomplishments.

Reflective journals: unmasking student perceptions of anatomical education.

PubMed

Lazarus, L; Sookrajh, R; Satyapal, K S

2017-01-01

In medical education, reflection has been considered to be a core skill in professional competence. The anatomy laboratory is an ideal setting for faculty/ student interaction and provides invaluable opportunities for active learning and reflection on anatomical knowledge. This study was designed to record student attitudes regarding human cadaveric dissection, explore their experiences of anatomy through an analysis of their journal-reflective writings and determine whether this type of creative writing had a beneficial effect on those students who chose to complete them. A total of 75 journals from Medical and Allied Health Science students were collected and analysed. Results were categorised according to the following themes: (i) Dissecting room stressors (27.6%); (ii) Educational value of dissection (26.3%); (iii) Appreciation, Gratitude, Respect and Curiosity for the cadaver (18.9%); (iv) Positive and negative sentiments expressed in the dissecting room (25.8%); (v) Benefit of alternate teaching modalities (4.6%); (vi) Spirituality/Religious Beliefs (3.7%); (vii) Shared humanity and emotional bonds (3.69%); (viii) Acknowledgement of human anatomical variations (3.2%); (ix) Beauty and complexity of the human body (1.8%) and (x) Psychological detachment (0.9%). Students appreciated the opportunity to share their emotions and reflect on the humanistic dimension of anatomy as a subject. Student reflections illustrated clearly their thoughts and some of the difficult issues with which they wrestled. The anatomy laboratory is seen as the budding clinician's first encounter with a patient, albeit a cadaver. This was the first time that reflective journals were given to students in the discipline. Reflective journals allow students to express themselves in an open-ended and creative fashion. It also assists students to integrate anatomy and clinical medicine and assists in applying their basic anatomical knowledge in an authentic, yet safe environment.

[Alternatives to femtosecond laser technology: subnanosecond UV pulse and ring foci for creation of LASIK flaps].

PubMed

Vogel, A; Freidank, S; Linz, N

2014-06-01

In refractive corneal surgery femtosecond (fs) lasers are used for creating LASIK flaps, dissecting lenticules and for astigmatism correction by limbal incisions. Femtosecond laser systems are complex and expensive and cutting precision is compromised by the large focal length associated with the commonly used infrared (IR) wavelengths. Based on investigations of the cutting dynamics, novel approaches for corneal dissection using ultraviolet A (UVA) picosecond (ps) pulses and ring foci from vortex beams are presented. Laser-induced bubble formation in corneal stroma was investigated by high-speed photography at 1-50 million frames/s. Using Gaussian and vortex beams of UVA pulses with durations between 200 and 850 ps the laser energy needed for easy removal of flaps created in porcine corneas was determined and the quality of the cuts by scanning electron microscopy was documented. Cutting parameters for 850 ps are reported also for rabbit eyes. The UV-induced and mechanical stress were evaluated for Gaussian and vortex beams. The results show that UVA picosecond lasers provide better cutting precision than IR femtosecond lasers, with similar processing times. Cutting energy decreases by >50 % when the laser pulse duration is reduced to 200 ps. Vortex beams produce a short, donut-shaped focus allowing efficient and precise dissection along the corneal lamellae which results in a dramatic reduction of the absorbed energy needed for cutting and of mechanical side effects as well as in less bubble formation in the cutting plane. A combination of novel approaches for corneal dissection provides the option to replace femtosecond lasers by compact UVA microchip laser technology. Ring foci are also of interest for femtosecond laser surgery, especially for improved lenticule excision.

From head to tail: new models and approaches in primate functional anatomy and biomechanics.

PubMed

Organ, Jason M; Deleon, Valerie B; Wang, Qian; Smith, Timothy D

2010-04-01

This special issue of The Anatomical Record (AR) is based on interest generated by a symposium at the 2008 annual meeting of the American Association of Anatomists (AAA) at Experimental Biology, entitled "An Evolutionary Perspective on Human Anatomy." The development of this volume in turn provided impetus for a Biological Anthropology Mini-Meeting, organized by members of the AAA for the 2010 Experimental Biology meeting in Anaheim, California. The research presented in these pages reflects the themes of these symposia and provides a snapshot of the current state of primate functional anatomy and biomechanics research. The 17 articles in this special issue utilize new models and/or approaches to study long-standing questions about the evolution of our closest relatives, including soft-tissue dissection and microanatomical techniques, experimental approaches to morphology, kinematic and kinetic biomechanics, high-resolution computed tomography, and Finite Element Analysis (FEA). This volume continues a close historical association between the disciplines of anatomy and biological anthropology: anatomists benefit from an understanding of the evolutionary history of our modern form, and biological anthropologists rely on anatomical principles to make informed evolutionary inferences about our closest relatives. (c) 2010 Wiley-Liss, Inc.

Talking about death: implementing peer discussion as a coping mechanism to overcome fears about dissection, death, and dying.

PubMed

Kotzé, Sanet Henriët; Mole, Calvin Gerald

2013-01-01

Many studies have reported on the perceptions of medical students toward dissection. It is important to understand the feelings and symptoms experienced during dissection so that they can be adequately handled. Prior to dissection, first year students are given lectures on aspects of dissection, death and dying, and death rituals in various cultures. Two separate questionnaires, one given during the first week of dissection and another given one month into the program were then completed anonymously by dissection groups. The questions were designed to be open-ended, thereby encouraging group discussion amongst students. The questionnaires were used to determine the perception of students to dissection and to discover if these perceptions change during the dissection program. The first questionnaire revealed that students do experience fears and anxiety prior to and at the beginning of dissection; however, most of these fears dissipated by the time of the second questionnaire. One month into dissection students cited talking to peers as their main coping mechanism and fewer students mentioned emotional detachment from their cadaver as a coping mechanism, as was the case in the first questionnaire. Dissection was perceived as a positive experience by our student cohort and most students cited the main advantage of dissection as the ability to visualize organs in three dimensions. The comprehensive answers received from the students indicated that thorough discussion of feelings amongst peers occurred, introducing students to an important coping mechanism at an early stage of their learning. Copyright © 2012 American Association of Anatomists.

Are all hands-on activities equally effective? Effect of using plastic models, organ dissections, and virtual dissections on student learning and perceptions.

PubMed

Lombardi, Sara A; Hicks, Reimi E; Thompson, Katerina V; Marbach-Ad, Gili

2014-03-01

This study investigated the impact of three commonly used cardiovascular model-assisted activities on student learning and student attitudes and perspectives about science. College students enrolled in a Human Anatomy and Physiology course were randomly assigned to one of three experimental groups (organ dissections, virtual dissections, or plastic models). Each group received a 15-min lecture followed by a 45-min activity with one of the treatments. Immediately after the lesson and then 2 mo later, students were tested on anatomy and physiology knowledge and completed an attitude survey. Students who used plastic models achieved significantly higher overall scores on both the initial and followup exams than students who performed organ or virtual dissections. On the initial exam, students in the plastic model and organ dissection treatments scored higher on anatomy questions than students who performed virtual dissections. Students in the plastic model group scored higher than students who performed organ dissections on physiology questions. On the followup exam, when asked anatomy questions, students in the plastic model group scored higher than dissection students and virtual dissection students. On attitude surveys, organ dissections had higher perceived value and were requested for inclusion in curricula twice as often as any other activity. Students who performed organ dissections were more likely than the other treatment groups to agree with the statement that "science is fun," suggesting that organ dissections may promote positive attitudes toward science. The findings of this study provide evidence for the importance of multiple types of hands-on activities in anatomy laboratory courses.

Diagnostic implication of fibrin degradation products and D-dimer in aortic dissection

NASA Astrophysics Data System (ADS)

Dong, Jian; Duan, Xianli; Feng, Rui; Zhao, Zhiqing; Feng, Xiang; Lu, Qingsheng; Jing, Qing; Zhou, Jian; Bao, Junmin; Jing, Zaiping

2017-03-01

Fibrin degradation products (FDP) and D-dimer have been considered to be involved in many vascular diseases. In this study we aimed to explore the diagnostic implication of FDP and D-dimer in aortic dissection patients. 202 aortic dissection patients were collected as the case group, 150 patients with other cardiovascular diseases, including myocardial infarction (MI, n = 45), pulmonary infarction (n = 51) and abdominal aortic aneurysm (n = 54) were collected as non-dissection group, and 27 healthy people were in the blank control group. The FDP and D-dimer levels were detected with immune nephelometry. Logist regression analysis was performed to evaluate the influence of FDP and D-dimer for the aortic dissection patients. ROC curve was used to determine the diagnostic value of FDP and D-dimer. The FDP and D-dimer levels were significantly higher in aortic dissection patients than in non-dissection patients and the healthy controls. FDP and D-dimer were both the risk factors for patients with aortic dissection. From the ROC analysis, diagnostic value of FDP and D-dimer were not high to distinguish aortic dissection patients from the non-dissection patients. However FDP and D-dimer could be valuable diagnostic marker to differentiate aortic dissection patients and healthy controls with both AUC 0.863.

Medical Student Dissection of Cadavers Improves Performance on Practical Exams but not on the NBME Anatomy Subject Exam.

PubMed

Sargent Jones, Leslie; Paulman, Lance E; Thadani, Raj; Terracio, Louis

2001-12-01

We have examined whether cadaver dissection by first year medical students (MIs) affected their performance in two test measures: the NBME Gross Anatomy and Embryology Subject Exam (dissection-relevant questions only), and practical exams given at the end of each major section within the course. The dissections for the entire course were divided into 18 regional dissection units and each student was assigned to dissect one third of the regional units; the other two-thirds of the material was learned from the partner-prosected cadavers. Performance for each student on the exams was then assessed as a function of the regions those students actually dissected. While the results indicated a small performance advantage for MIs answering questions on material they had dissected on the NBME Subject Exam questions relevant to dissection (78-88% of total exam), the results were not statistically significant. However, a similar, small performance advantage on the course practical exams was highly significant.

Pathway-focused bioassays and transcriptome analysis contribute to a better activity monitoring of complex herbal remedies

PubMed Central

2013-01-01

Background Transcriptome analysis in combination with pathway-focused bioassays is suggested to be a helpful approach for gaining deeper insights into the complex mechanisms of action of herbal multicomponent preparations in living cells. The polyherbalism based concept of Tibetan and Ayurvedic medicine considers therapeutic efficacy through multi-target effects. A polyherbal Indo-Tibetan preparation, Padma 28, approved by the Swiss drug authorities (Swissmedic Nr. 58436), was applied to a more detailed dissection of mechanism of action in human hepatoma HepG2 cells. Cell-free and cell-based assays were employed to evaluate the antioxidant capacity. Genome-wide expression profiling was done by applying Human Genome U133 Plus 2.0 Affymetrix arrays. Pathway- and network-oriented analysis elucidated the affected biological processes. The results were validated using reporter gene assays and quantitative real-time PCR. Results To reveal the direct radical scavenging effects of the ethanolic extract of the Indo-Tibetan polyherbal remedy Padma 28, an in vitro oxygen radical absorbance capacity assay (ORAC) was employed, which resulted in a peroxyl-radical scavenging activity of 2006 ± 235 μmol TE/g. Furthermore, the antioxidant capacity of Padma 28 was analysed in living HepG2 cells, by measuring its scavenging potential against radical induced ROS. This formulation showed a considerable antioxidant capacity by significantly reducing ROS levels in a dose-dependent manner. Integrated transcriptome analysis revealed a major influence on phase I and phase II detoxification and the oxidative stress response. Selected target genes, such as heme oxygenase 1, were validated in qPCR experiments. Network analysis showed 18 interrelated networks involved in important biological functions such as drug and bio-molecule metabolism, molecular transport and cellular communication. Some molecules are part of signaling cascades that are active during development and morphogenesis or are involved in pathological conditions and inflammatory response. Conclusions The identified molecular targets and pathways suggest several mechanisms that underlie the biological activity of the preparation. Although extrapolation of these findings to the in vivo situation is not possible, the results obtained might be the basis for further investigations and new hypotheses to be tested. This study demonstrates the potential of the combination of focused and unbiased research strategies in the mode of action analysis of multicomponent herbal mixtures. PMID:23445205

Topological analysis of metabolic networks integrating co-segregating transcriptomes and metabolomes in type 2 diabetic rat congenic series.

PubMed

Dumas, Marc-Emmanuel; Domange, Céline; Calderari, Sophie; Martínez, Andrea Rodríguez; Ayala, Rafael; Wilder, Steven P; Suárez-Zamorano, Nicolas; Collins, Stephan C; Wallis, Robert H; Gu, Quan; Wang, Yulan; Hue, Christophe; Otto, Georg W; Argoud, Karène; Navratil, Vincent; Mitchell, Steve C; Lindon, John C; Holmes, Elaine; Cazier, Jean-Baptiste; Nicholson, Jeremy K; Gauguier, Dominique

2016-09-30

The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge. Here, we introduce a systems genetics approach based on the topological analysis of a combined molecular network made of genes and metabolites identified through expression and metabotype quantitative trait locus mapping (i.e., eQTL and mQTL) to prioritise biological characterisation of candidate genes and traits. We used systematic metabotyping by 1 H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualize the shortest paths between metabolites and genes significantly associated with each genomic block. Despite strong genomic similarities (95-99 %) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting the metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific mQTLs and genome-wide eQTLs. Variation in key metabolites like glucose, succinate, lactate, or 3-hydroxybutyrate and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing the shortest path length drove prioritization of biological validations by gene silencing. These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulation and to characterize novel functional roles for genes determining tissue-specific metabolism.

Role of Klotho in Osteoporosis and Renal Osteodystrophy

DTIC Science & Technology

2014-10-01

about the complex physiology of bone development and maintenance including the endocrine regulation of mineral homeostasis that is absolutely...percentage of bone. This should enhance the effects we have already seen in other lines and enable us to delve further into physiology of the phenotype...Klotho and FGFRs [11,12]. To dissect the role of parathyroid gland resident Klotho in physiology and in pathophysiological states such as CKD, we

Reconstitution of active human core Mediator complex reveals a pivotal role of the MED14 subunit

PubMed Central

Cevher, Murat A.; Shi, Yi; Li, Dan; Chait, Brian T.; Malik, Sohail; Roeder, Robert G.

2014-01-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here, we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to mass spectrometry (CX-MS). Whereas the reconstituted head and middle modules can stably associate, only with incorporation of MED14 into the bi-modular complex does it acquire basal and coactivator functions. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematically dissecting the multiple layers of functionalities associated with the Mediator complex. PMID:25383669

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity

NASA Astrophysics Data System (ADS)

Wenthur, Cody J.; Zhou, Bin; Janda, Kim D.

2017-08-01

Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and ‘pharmacoterrorism’ in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system. Although the psychoactive properties of fenethylline have been reported to differ from those of other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. Here we develop a ‘dissection through vaccination’ approach, called DISSECTIV, to mitigate the psychoactive effects of fenethylline and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against a single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacological activity. We anticipate that DISSECTIV will be used to expose unidentified active chemical species and resolve pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples and natural product extracts.

Vaccine-driven pharmacodynamic dissection and mitigation of fenethylline psychoactivity.

PubMed

Wenthur, Cody J; Zhou, Bin; Janda, Kim D

2017-08-24

Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and 'pharmacoterrorism' in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system. Although the psychoactive properties of fenethylline have been reported to differ from those of other synthetic stimulants, the in vivo chemical complexity it manifests upon ingestion has impeded efforts to unambiguously identify the specific species responsible for these effects. Here we develop a 'dissection through vaccination' approach, called DISSECTIV, to mitigate the psychoactive effects of fenethylline and show that its rapid-onset and distinct psychoactive properties are facilitated by functional synergy between theophylline and amphetamine. Our results demonstrate that incremental vaccination against a single chemical species within a multi-component mixture can be used to uncover emergent properties arising from polypharmacological activity. We anticipate that DISSECTIV will be used to expose unidentified active chemical species and resolve pharmacodynamic interactions within other chemically complex systems, such as those found in counterfeit or illegal drug preparations, post-metabolic tissue samples and natural product extracts.

The burden of poofs: criminal pathology, clinical scrutiny, and homosexual etiology in queer cinema.

PubMed

Wahlert, Lance

2013-06-01

Given the resurgence of scientific studies on the etiology of homosexuality in the wake of the AIDS epidemic, this article considers the effects these studies had on contemporaneous queer filmmakers. By using the subject of criminality as a way to talk about homosexual causality, queer films of the 1990s illustrate that contemporary scientific studies on homosexuality were historically and politically situated in relation to cultural anxieties about other forms of deviance. This article focuses on films that dissect the hetero-normative tendency to amalgamate forms of deviance in order to distinguish between the diseased and the healthy. Such products of New Queer Cinema highlight this amalgamation of criminality and homosexuality in order to challenge demands by the LGBT community of the 1980s and 1990s for "more positive images" in film. This article argues that queer filmmakers have manipulated the image of the queer criminal to usurp the medical tendency to biologize and pathologize the notion of queer transgression. In such a way, queer films that enthusiastically dramatize the queer outlaw perpetuate myths about homosexuality in order to dissect and discredit them.

Prediction and Dissection of Protein-RNA Interactions by Molecular Descriptors.

PubMed

Liu, Zhi-Ping; Chen, Luonan

2016-01-01

Protein-RNA interactions play crucial roles in numerous biological processes. However, detecting the interactions and binding sites between protein and RNA by traditional experiments is still time consuming and labor costing. Thus, it is of importance to develop bioinformatics methods for predicting protein-RNA interactions and binding sites. Accurate prediction of protein-RNA interactions and recognitions will highly benefit to decipher the interaction mechanisms between protein and RNA, as well as to improve the RNA-related protein engineering and drug design. In this work, we summarize the current bioinformatics strategies of predicting protein-RNA interactions and dissecting protein-RNA interaction mechanisms from local structure binding motifs. In particular, we focus on the feature-based machine learning methods, in which the molecular descriptors of protein and RNA are extracted and integrated as feature vectors of representing the interaction events and recognition residues. In addition, the available methods are classified and compared comprehensively. The molecular descriptors are expected to elucidate the binding mechanisms of protein-RNA interaction and reveal the functional implications from structural complementary perspective.

Dissecting disease entities out of the broad spectrum of bipolar-disorders.

PubMed

Levine, Joseph; Toker, Lilach; Agam, Galila

2018-01-01

The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.

Light-activated regulation of cofilin dynamics using a photocaged hydrogen peroxide generator.

PubMed

Miller, Evan W; Taulet, Nicolas; Onak, Carl S; New, Elizabeth J; Lanselle, Julie K; Smelick, Gillian S; Chang, Christopher J

2010-12-08

Hydrogen peroxide (H2O2) can exert diverse signaling and stress responses within living systems depending on its spatial and temporal dynamics. Here we report a new small-molecule probe for producing H2O2 on demand upon photoactivation and its application for optical regulation of cofilin-actin rod formation in living cells. This chemical method offers many potential opportunities for dissecting biological roles for H2O2 as well as remote control of cell behavior via H2O2-mediated pathways.

In Silico Approaches and the Role of Ontologies in Aging Research

PubMed Central

Boerries, Melanie; Busch, Hauke; de Grey, Aubrey; Hahn, Udo; Hiller, Thomas; Hoeflich, Andreas; Jansen, Ludger; Janssens, Georges E.; Kaleta, Christoph; Meinema, Anne C.; Schäuble, Sascha; Simm, Andreas; Schofield, Paul N.; Smith, Barry; Sühnel, Juergen; Vera, Julio; Wagner, Wolfgang; Wönne, Eva C.; Wuttke, Daniel

2013-01-01

Abstract The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, because these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focused on marker development and cellular stress as well as on diseases, in particular on diseases of kidney and skin. PMID:24188080

Sentinel Node Biopsy in Melanoma: A Short Update

PubMed Central

Ferrara, Gerardo; Partenzi, Antonietta; Filosa, Alessandra

2018-01-01

Several controversies are still ongoing about sentinel node biopsy in melanoma. It is basically a staging procedure for melanoma > 0.75 mm in thickness or for thinner melanoma in the presence of ulceration, high mitotic rate, and/or lymphovascular invasion. Complete lymph node dissection after a positive sentinel node can also allow a better locoregional disease control but seems not to prevent the development of distant metastases. The use of sentinel node biopsy in atypical Spitz tumors should be discouraged because of their peculiar biological properties. PMID:29719827

A New Approach to Dissect Nuclear Organization: TALE-Mediated Genome Visualization (TGV).

PubMed

Miyanari, Yusuke

2016-01-01

Spatiotemporal organization of chromatin within the nucleus has so far remained elusive. Live visualization of nuclear remodeling could be a promising approach to understand its functional relevance in genome functions and mechanisms regulating genome architecture. Recent technological advances in live imaging of chromosomes begun to explore the biological roles of the movement of the chromatin within the nucleus. Here I describe a new technique, called TALE-mediated genome visualization (TGV), which allows us to visualize endogenous repetitive sequence including centromeric, pericentromeric, and telomeric repeats in living cells.

Using Magnets and Magnetic Beads to Dissect Signaling Pathways Activated by Mechanical Tension Applied to Cells

PubMed Central

Marjoram, R.J.; Guilluy, C; Burridge, K.

2015-01-01

Cellular tension has implications in normal biology and pathology. Membrane adhesion receptors serve as conduits for mechanotransduction that lead to cellular responses. Ligand-conjugated magnetic beads are a useful tool in the study of how cells sense and respond to tension. Here we detail methods for their use in applying tension to cells and strategies for analyzing the results. We demonstrate the methods by analyzing mechanotransduction through VE-cadherin on endothelial cells using both permanent magnets and magnetic tweezers. PMID:26427549

Retrograde Ascending Aortic Dissection after Stent Grafting for Stanford Type B Aortic Dissection with Severe Limb Ischemia.

PubMed

Higuchi, Yoshiro; Tochii, Masato; Takami, Yoshiyuki; Kobayashi, Akihiro; Yanagisawa, Tsutomu; Amano, Kentaro; Sakurai, Yusuke; Ishida, Michiko; Ishikawa, Hiroshi; Hattori, Koji; Takagi, Yasushi

2017-03-24

We report a rare case of retrograde Stanford type A aortic dissection after endovascular repair for complicated Stanford type B aortic dissection. A 45-year-old man presented with a sudden onset of back pain and was transferred to our hospital. Computed tomography demonstrated acute Stanford type B aortic dissection with lower limb ischemia. Emergency endovascular surgery was planned for repair of the Stanford type B aortic dissection. The patient suddenly developed recurrent chest pain 10 days after the initial procedure. Computed tomography revealed retrograde Stanford type A aortic dissection involving the ascending aorta and aortic arch. The patient underwent a successful emergency total aortic arch replacement.

Talking about Death: Implementing Peer Discussion as a Coping Mechanism to Overcome Fears about Dissection, Death, and Dying

ERIC Educational Resources Information Center

Kotze, Sanet Henriet; Mole, Calvin Gerald

2013-01-01

Many studies have reported on the perceptions of medical students toward dissection. It is important to understand the feelings and symptoms experienced during dissection so that they can be adequately handled. Prior to dissection, first year students are given lectures on aspects of dissection, death and dying, and death rituals in various…

Partial lower axillary dissection for patients with clinically node-negative breast cancer.

PubMed

Kodama, H; Mise, K; Kan, N

2012-01-01

To evaluate retrospectively the outcomes of partial lower axillary lymph node dissection caudal to the intercostobrachial nerve in patients with clinically node-negative (N(0)) breast cancer. Numbers of dissected and metastatic nodes, overall and disease-free survival rates, postoperative complication rates, and axillary recurrence were compared between patients who underwent breast cancer surgery with partial axillary node dissection (n = 1043) and historical controls who underwent conventional dissection (n = 1084). The 5-year overall and disease-free survival rates were 95.6% and 89.7%, and 94.9% and 88.4%, respectively, in the partial dissection and conventional dissection groups; the differences were not significant. Mean duration of surgery (41.6 min versus 60.9 min), intraoperative blood loss (28.0 ml versus 51.3 ml), volume of lymphatic drainage at 2 weeks postoperatively (488 ml versus 836 ml), and persistent arm lymphoedema (0.0% versus 11.8%) were significantly different between the partial and conventional dissection groups, respectively. Partial axillary lymph node dissection was associated with similar survival rates (but lower postoperative complication rates) compared with conventional axillary dissection and is recommended in patients with N(0) breast cancer.

The complementary role of magnetic resonance imaging, Doppler echocardiography, and computed tomography in the diagnosis of dissecting thoracic aneurysms.

PubMed

Goldman, A P; Kotler, M N; Scanlon, M H; Ostrum, B; Parameswaran, R; Parry, W R

1986-05-01

Non-ECG gated MRI was compared with 2DE and/or CT scans in 10 patients with dissecting aneurysms proven by angiography and/or surgery. Patient ages ranged from 48 to 85 years (mean 69.6). Six had DeBakey type I dissections and four had DeBakey type III dissections. MRI was diagnostic for aortic dissection in nine cases and suggestive in the tenth. 2DE was diagnostic in six out of nine patients, suggestive in two patients, and nondiagnostic in one patient. CT was diagnostic in the three cases in which it was employed. MRI demonstrated a dilated ascending aorta with thickened walls in all type I dissections as well as an intimal flap and slow flow in the false channel in four patients. In the other two patients with type I dissection, MRI detected the intimal flap in the descending aorta but not in the ascending aorta, whereas 2DE revealed the ascending aortic intimal flap in both of these patients and CT showed it in one of them. In the type III dissections, MRI demonstrated a thickened wall and thrombus in the lumen in all four cases, and the intimal flap in three out of the four. 2DE excluded ascending aortic involvement in all three type III dissections. Six other patients with fusiform dilated ascending aortas had no evidence of dissection by MRI, 2DE, and aortography. Thus, non-ECG gated MRI alone or in combination with 2DE and/or CT is useful in the diagnosis of dissecting thoracic aneurysm and in assessing the extent of the dissection. In addition, the differentiation of dissecting aneurysms of the aorta from fusiform dilatation of the aorta is made possible by these noninvasive techniques.

Synthesis and evaluation of carbocyanine dyes as PRMT inhibitors and imaging agents.

PubMed

Sinha, Sarmistha Halder; Owens, Eric A; Feng, You; Yang, Yutao; Xie, Yan; Tu, Yaping; Henary, Maged; Zheng, Yujun George

2012-08-01

Protein arginine methylation regulates multiple biological processes. Deregulation of protein arginine methyltransferase (PRMT) activities has been observed in many disease phenotypes. Small molecule probes that target PRMTs with strong affinity and selectivity can be used as valuable tools to dissect biological mechanisms of arginine methylation and establish the role of PRMT proteins in a disease process. In this work, we report synthesis and evaluation of a class of carbocyanine compounds containing indolium, benz[e]indolium or benz[c,d]indolium heterocyclic moieties that bind to the predominant arginine methyltransferase PRMT1 and inhibit its methyltransferase activity at low micromolar potencies. In particular, the developed molecules have long wavelength colorimetric and fluorometric photoactivities, which can be used for optical and near-infrared fluorescence imaging in cells or biological tissues. Together, these new chemical probes have potential application in PRMT studies both as enzyme inhibitors and as fluorescent dyes for microscope imaging. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Life lines: An art history of biological research around 1800.

PubMed

Bruhn, Matthias

2011-12-01

Around 1800, the scientific "illustrator" emerged as a new artistic profession in Europe. Artists were increasingly sought after in order to picture anatomical dissections and microscopic observations and to translate drawings into artworks for books and journals. By training and technical expertise, they introduced a particular kind of knowledge into scientific perception that also shaped the common image of nature. Illustrations of scientific publications, often undervalued as a biased interpretation of facts and subordinate to logic and description, thus convey an 'art history' of science in its own right, relevant both for the understanding of biological thought around 1800 as well as for the development of the arts and their historiography. The article is based on an analysis of botanical treatises produced for the Göttingen Society of Sciences in 1803, during an early phase of microscopic cell research, in order to determine the constitutive role of artistic knowledge and the media employed for the visualization and conceptualization of biological issues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Microchip-Based Single-Cell Functional Proteomics for Biomedical Applications

PubMed Central

Lu, Yao; Yang, Liu; Wei, Wei; Shi, Qihui

2017-01-01

Cellular heterogeneity has been widely recognized but only recently have single cell tools become available that allow characterizing heterogeneity at the genomic and proteomic levels. We review the technological advances in microchip-based toolkits for single-cell functional proteomics. Each of these tools has distinct advantages and limitations, and a few have advanced toward being applied to address biological or clinical problems that fail to be addressed by traditional population-based methods. High-throughput single-cell proteomic assays generate high-dimensional data sets that contain new information and thus require developing new analytical framework to extract new biology. In this review article, we highlight a few biological and clinical applications in which the microchip-based single-cell proteomic tools provide unique advantages. The examples include resolving functional heterogeneity and dynamics of immune cells, dissecting cell-cell interaction by creating well-contolled on-chip microenvironment, capturing high-resolution snapshots of immune system functions in patients for better immunotherapy and elucidating phosphoprotein signaling networks in cancer cells for guiding effective molecularly targeted therapies. PMID:28280819

Experiences with dissection courses in human anatomy: a comparison between Germany and Ethiopia.

PubMed

Bekele, Assegedech; Reissig, Dieter; Löffler, Sabine; Hinz, Andreas

2011-03-01

Dissection courses in human anatomy are laborious, and new teaching tools have become available. Therefore, some universities intend to reduce the dissection course. Furthermore, little is known about dissection courses in African universities. The aim of this study is to compare the students' experiences with and evaluations of the dissection courses in two universities: Leipzig (Germany) and Gondar (Ethiopia). Since the Gondar Medical College was founded in cooperation with the Leipzig University in 1978, the anatomy courses in both universities follow roughly the same rules. A structured questionnaire was used to assess the dissection courses from the students' point of view. The sample of students consisted of 109 German and 124 Ethiopian first year undergraduate medical students. Most students in both countries (94% in Germany and 82% in Ethiopia) judge the dissection course to be highly relevant compared to other courses. Perceived health hazards associated with dissection of the cadaver show significant differences between Germany (14%) and Ethiopia (44%). Most students had normal feelings again at the end of the dissection course. Further similarities and differences between the courses in Germany and Ethiopia are described. Dissection courses are highly appreciated also in Africa. The high degree of affirmation of the dissection courses should be taken into consideration when discussing modifications of gross anatomy curriculum or changes in the teacher to student ratio. Copyright © 2010 Elsevier GmbH. All rights reserved.

Visualizing Science Dissections in 3D: Contextualizing Student Responses to Multidimensional Learning Materials in Science Dissections

NASA Astrophysics Data System (ADS)

Walker, Robin Annette

A series of dissection tasks was developed in this mixed-methods study of student self-explanations of their learning using actual and virtual multidimensional science dissections and visuo-spatial instruction. Thirty-five seventh-grade students from a science classroom (N = 20 Female/15 Male, Age =13 years) were assigned to three dissection environments instructing them to: (a) construct static paper designs of frogs, (b) perform active dissections with formaldehyde specimens, and (c) engage with interactive 3D frog visualizations and virtual simulations. This multi-methods analysis of student engagement with anchored dissection materials found learning gains on labeling exercises and lab assessments among most students. Data revealed that students who correctly utilized multimedia text and diagrams, individually and collaboratively, manipulated 3D tools more effectively and were better able to self-explain and complete their dissection work. Student questionnaire responses corroborated that they preferred learning how to dissect a frog using 3D multimedia instruction. The data were used to discuss the impact of 3D technologies, programs, and activities on student learning, spatial reasoning, and their interest in science. Implications were drawn regarding how to best integrate 3D visualizations into science curricula as innovative learning options for students, as instructional alternatives for teachers, and as mandated dissection choices for those who object to physical dissections in schools.

Scoping review of the literature on shoulder impairments and disability after neck dissection.

PubMed

Goldstein, David P; Ringash, Jolie; Bissada, Eric; Jaquet, Yves; Irish, Jonathan; Chepeha, Douglas; Davis, Aileen M

2014-02-01

The purpose of this article was to provide a review of the literature on shoulder disability after neck dissection. A literature review was performed using Ovid Medline and Embase databases. A total of 306 abstracts and 78 full-text articles were reviewed. Forty-two articles were eligible for inclusion. Patients undergoing nerve-sacrifice neck dissections have greater disability and lower quality of life scores than those undergoing neck dissections with the least manipulation (ie, selective neck dissections). Shoulder impairments can still occur in patients undergoing selective neck dissections. Disability typically improves over time in patients undergoing nerve-sparing neck dissections. There was significant variability in the literature in terms of the prevalence and recovery of shoulder morbidity after neck dissection. This variability may not just be related to surgical technique or rehabilitation, but also to study design, definitions, and the variability in disability questionnaires used. Copyright © 2013 Wiley Periodicals, Inc.

78 FR 58311 - Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-23

...] Complex Issues in Developing Drug and Biological Products for Rare Diseases; Public Workshop; Request for... Issues in Developing Drug and Biological Products for Rare Diseases.'' The purpose of the public workshop is twofold: To discuss complex issues in clinical trials for developing drug and biological products...

The utility of cadaver dissection in endoscopic sinus surgery training courses.

PubMed

Zuckerman, Jodi D; Wise, Sarah K; Rogers, G Aaron; Senior, Brent A; Schlosser, Rodney J; DelGaudio, John M

2009-01-01

Understanding paranasal sinus anatomy is crucial for successful outcomes in endoscopic sinus surgery (ESS). This study was designed to evaluate subjective and objective differences in ESS cadaver dissections among participants of varying experience levels in association with the use of image guidance and computer-aided technologies in a physician training cadaver dissection laboratory. Participants in a 2-day cadaver dissection course completed daily predissection surveys evaluating subjective comfort with ESS. Pre- and postdissection computer tomography (CT) scans assessed completeness of dissection. Images were analyzed for maxillary antrostomy, frontal and sphenoid sinusotomy, residual ethmoid cells and partitions, and residual frontal recess cells. Fifty-one sides were dissected. Participant comfort increased significantly from day 1 to 2 for overall ESS (p = 0.001) and for individual sinuses (p < 0.001 to p = 0.047). Participants with more years in practice had fewer unopened ethmoid cells (p = 0.015) and frontal recess cells (p = 0.014) on dissection day 1. Participants with increased comfort in ethmoid dissection had fewer retained ethmoid partitions on day 1 (p = 0.017). Observed differences on dissection day 1 for unopened ethmoid and frontal recess cells and retained ethmoid partitions were not present on day 2. No significant differences were found based on use of image guidance for any parameter. Surgeons with increased comfort and more years in practice had more complete endoscopic cadaver dissections initially. Differences among participants diminished on dissection day 2, indicating the ability to review postdissection CT scans may improve surgeon comfort level and completeness of dissection.

[Progress and challenge of Stanford type A aortic dissection in China].

PubMed

Sun, L Z; Li, J R

2017-04-01

In recent 20 years, the rapid development of acute Stanford type A aortic dissection in China has been mainly due to three aspects: (1) the refined classification of aortic dissection based on Stanford classification, (2) right axillary artery canal and selective cerebral perfusion technology become basic cardiopulmonary bypass strategy for Stanford type A aortic dissection, and (3) total aortic arch replacement and descending aortic stent graft surgery (Sun's surgery) become the standard treatment of Stanford type A aortic dissection. However, there are still many problems in the diagnosis and treatment of aortic dissection in China, such as: (1) unstandardized, lack of comprehensive guidelines of aortic dissection, (2) immature, perioperative organ protection and intraoperative blood protection technology remains a big flaw, and (3) it takes a long time to get patient prepared for surgery. In conclusion, as to the issue of the management of acute Stanford type A aortic dissection, there will be a long way for Chinese doctors to go. Peers should pay more attention to this problem and take more efforts, so that the outcome of acute Stanford type A aortic dissection surgical patients can be improved.

Video-assisted thoracic surgery for left upper lobectomy for complex lesions: how to extend the indication with optimal safety?

PubMed

Bayard, Nathanaël Frank; Barnett, Stephen Arthur; Rinieri, Philippe; Melki, Jean; Peillon, Christophe; Baste, Jean Marc

2016-08-01

The feasibility of extending the VATS approach to locally advanced NSCLC has been described with good clinical outcome. These complex resections are still technically challenging and patient safety must remain the highest priority. In this article, we describe our routine VATS approach for left upper lobectomy in proximal, locally advanced lesions. Both surgical and anaesthesiology teams are trained during simulation sessions to respond rapidly in case of urgent thoracotomy. Encircling arterial and venous vessels allow control of inadvertent bleeding during difficult dissection. Also, whenever needed the double vessel control technique is a time saver waiting for conversion to thoracotomy.

Arthroscopic-Assisted Triangular Fibrocartilage Complex Reconstruction.

PubMed

Chu-Kay Mak, Michael; Ho, Pak-Cheong

2017-11-01

Injury of the triangular fibrocartilage complex (TFCC) is a common cause of ulnar-sided wrist pain. Volar and dorsal radioulnar ligaments and their foveal insertion are the most important stabilizing components of the TFCC. In irreparable tears, anatomic reconstruction of the TFCC aims to restore normal biomechanics and stability of the distal radioulnar joint. We proposed a novel arthroscopic-assisted technique using a palmaris longus tendon graft. Arthroscopic-assisted TFCC reconstruction is a safe and effective approach with outcomes comparable to conventional open reconstruction and may result in a better range of motion from minimizing soft tissue dissection and subsequent scarring. Copyright © 2017 Elsevier Inc. All rights reserved.

NEW MOLECULAR MEDICINE-BASED SCAR MANAGEMENT STRATEGIES

PubMed Central

Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

2014-01-01

Keloids and hypertrophic scars are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research has contributed to unravel new bench-to-bedside scar therapies, and to dissect the complex signaling pathways involved. Peptides such as transforming growth factor beta (TGF-β) superfamily, with SMADs, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-β4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scars. The aim of this review is to describe the basic complexity of these new molecular scar management strategies, and point out new fibrosis research lines. PMID:24438742

Do we need dissection in an integrated problem-based learning medical course? Perceptions of first- and second-year students.

PubMed

Azer, Samy A; Eizenberg, Norm

2007-03-01

The introduction of a problem-based learning (PBL) curriculum at the School of Medicine of the University of Melbourne has necessitated a reduction in the number of lectures and limited the use of dissection in teaching anatomy. In the new curriculum, students learn the anatomy of different body systems using PBL tutorials, practical classes, pre-dissected specimens, computer-aided learning multimedia and a few dissection classes. The aims of this study are: (1) to assess the views of first- and second-year medical students on the importance of dissection in learning about the anatomy, (2) to assess if students' views have been affected by demographic variables such as gender, academic background and being a local or an international student, and (3) to assess which educational tools helped them most in learning the anatomy and whether dissection sessions have helped them in better understanding anatomy. First- and second-year students enrolled in the medical course participated in this study. Students were asked to fill out a 5-point Likert scale questionnaire. Data was analysed using Mann-Whitney's U test, Wilcoxon's signed-ranks or the calculation of the Chi-square value. The response rates were 89% for both first- and second-year students. Compared to second-year students, first-year students perceived dissection to be important for deep understanding of anatomy (P < 0.001), making learning interesting (P < 0.001) and introducing them to emergency procedures (P < 0.001). Further, they preferred dissection over any other approach (P < 0.001). First-year students ranked dissection (44%), textbooks (23%), computer-aided learning (CAL), multimedia (10%), self-directed learning (6%) and lectures (5%) as the most valuable resources for learning anatomy, whereas second-year students found textbooks (38%), dissection (18%), pre-dissected specimens (11%), self-directed learning (9%), lectures (7%) and CAL programs (7%) as most useful. Neither of the groups showed a significant preference for pre-dissected specimens, CAL multimedia or lectures over dissection. Both first- and second-year students, regardless of their gender, academic background, or citizenship felt that the time devoted to dissection classes were not adequate. Students agreed that dissection deepened their understanding of anatomical structures, provided them with a three-dimensional perspective of structures and helped them recall what they learnt. Although their perception about the importance of dissection changed as they progressed in the course, good anatomy textbooks were perceived as an excellent resource for learning anatomy. Interestingly, innovations used in teaching anatomy, such as interactive multimedia resources, have not replaced students' perceptions about the importance of dissection.

Dissection videos do not improve anatomy examination scores.

PubMed

Mahmud, Waqas; Hyder, Omar; Butt, Jamaal; Aftab, Arsalan

2011-01-01

In this quasi-experimental study, we describe the effect of showing dissection videos on first-year medical students' performance in terms of test scores during a gross anatomy course. We also surveyed students' perception regarding the showing of dissection videos. Two hundred eighty-seven first-year medical students at Rawalpindi Medical College in Pakistan, divided into two groups, dissected one limb in first term and switched over to the other limb in the second term. During the second term, instruction was supplemented by dissection videos. Second-term anatomy examination marks were compared with first-term scores and with results from first-year medical students in previous years. Multiple linear regression analysis was performed, with term scores (continuous, 0-200) as the dependent variable. Students shown dissection videos scored 1.26 marks higher than those not shown. The relationship was not statistically significant (95% CI: -1.11, 3.70; P = 0.314). Ninety-three percent of students favored regular inclusion of dissection videos in curriculum, and 50% termed it the best source for learning gross anatomy. Seventy-six percent of students did not perform regular cadaver dissection. The most frequent reason cited for not performing regular dissection was high student-cadaver ratio. Dissection videos did not improve performance on final examination scores; however, students favored their use. Copyright © 2011 American Association of Anatomists.

The dissection room experience: A factor in the choice of organ and whole body donation--a Nigerian survey.

PubMed

Anyanwu, Emeka G; Obikili, Emmanuel N; Agu, Augustine U

2014-01-01

The psychosocial impact of human dissection on the lives of medical and health science students has been noted. To assess the impact of the dissection room experience on one's willingness to become a whole body and organ donor, the attitudes of 1,350 students and professionals from the medical, health, and non-health related disciplines to body and organ donation were studied. The participants were broken into categories according to degree of exposure to human dissection. Participants who were never exposed to the dissection experience showed more willingness to donate their bodies than those who were exposed. With the exception of the physiotherapy department, the students and professionals from the health science departments who were exposed to the dissection room but never engaged in dissection showed the most unwillingness to donate their bodies (P < 0.001). An unwillingness to donate oneself was noted as one of the negative impacts associated with exposure to the dissection room. Willingness to donate an organ correlated positively with the level of exposure to the dissection room (P < 0.001). Most of the reasons for unwillingness were traceable to negative perceptions of the dissection room as a result of poor and disrespectful management of the human cadavers. © 2013 American Association of Anatomists.

Identification of loci governing eight agronomic traits using a GBS-GWAS approach and validation by QTL mapping in soya bean.

PubMed

Sonah, Humira; O'Donoughue, Louise; Cober, Elroy; Rajcan, Istvan; Belzile, François

2015-02-01

Soya bean is a major source of edible oil and protein for human consumption as well as animal feed. Understanding the genetic basis of different traits in soya bean will provide important insights for improving breeding strategies for this crop. A genome-wide association study (GWAS) was conducted to accelerate molecular breeding for the improvement of agronomic traits in soya bean. A genotyping-by-sequencing (GBS) approach was used to provide dense genome-wide marker coverage (>47,000 SNPs) for a panel of 304 short-season soya bean lines. A subset of 139 lines, representative of the diversity among these, was characterized phenotypically for eight traits under six environments (3 sites × 2 years). Marker coverage proved sufficient to ensure highly significant associations between the genes known to control simple traits (flower, hilum and pubescence colour) and flanking SNPs. Between one and eight genomic loci associated with more complex traits (maturity, plant height, seed weight, seed oil and protein) were also identified. Importantly, most of these GWAS loci were located within genomic regions identified by previously reported quantitative trait locus (QTL) for these traits. In some cases, the reported QTLs were also successfully validated by additional QTL mapping in a biparental population. This study demonstrates that integrating GBS and GWAS can be used as a powerful complementary approach to classical biparental mapping for dissecting complex traits in soya bean. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

PubMed Central

Blackiston, Douglas; Shomrat, Tal; Nicolas, Cindy L.; Granata, Christopher; Levin, Michael

2010-01-01

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science. PMID:21179424

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles.

PubMed

Li, Ruohan; Harvey, Alan R; Hodgetts, Stuart I; Fox, Archa H

2017-06-01

Large numbers of long noncoding RNAs have been discovered in recent years, but only a few have been characterized. NEAT1 (nuclear paraspeckle assembly transcript 1) is a mammalian long noncoding RNA that is important for the reproductive physiology of mice, cancer development, and the formation of subnuclear bodies termed paraspeckles. The two major isoforms of NEAT1 (3.7 kb NEAT1_1 and 23 kb NEAT1_2 in human) are generated from a common promoter and are produced through the use of alternative transcription termination sites. This gene structure has made the functional relationship between the two isoforms difficult to dissect. Here we used CRISPR-Cas9 genome editing to create several different cell lines: total NEAT1 knockout cells, cells that only express the short form NEAT1_1, and cells with twofold more NEAT1_2. Using these reagents, we obtained evidence that NEAT1_1 is not a major component of paraspeckles. In addition, our data suggest NEAT1_1 localizes in numerous nonparaspeckle foci we termed "microspeckles," which may carry paraspeckle-independent functions. This study highlights the complexity of lncRNA and showcases how genome editing tools are useful in dissecting the structural and functional roles of overlapping transcripts. © 2017 Li et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Correlation between gross anatomical topography, sectional sheet plastination, microscopic anatomy and endoanal sonography of the anal sphincter complex in human males

PubMed Central

Al-Ali, S; Blyth, P; Beatty, S; Duang, A; Parry, B; Bissett, I P

2009-01-01

This study elucidates the structure of the anal sphincter complex (ASC) and correlates the individual layers, namely the external anal sphincter (EAS), conjoint longitudinal muscle (CLM) and internal anal sphincter (IAS), with their ultrasonographic images. Eighteen male cadavers, with an average age of 72 years (range 62–82 years), were used in this study. Multiple methods were used including gross dissection, coronal and axial sheet plastination, different histological staining techniques and endoanal sonography. The EAS was a continuous layer but with different relations, an upper part (corresponding to the deep and superficial parts in the traditional description) and a lower (subcutaneous) part that was located distal to the IAS, and was the only muscle encircling the anal orifice below the IAS. The CLM was a fibro-fatty-muscular layer occupying the intersphincteric space and was continuous superiorly with the longitudinal muscle layer of the rectum. In its middle and lower parts it consisted of collagen and elastic fibres with fatty tissue filling the spaces between the fibrous septa. The IAS was a markedly thickened extension of the terminal circular smooth muscle layer of the rectum and it terminated proximal to the lower part of the EAS. On endoanal sonography, the EAS appeared as an irregular hyperechoic band; CLM was poorly represented by a thin irregular hyperechoic line and IAS was represented by a hypoechoic band. Data on the measurements of the thickness of the ASC layers are presented and vary between dissection and sonographic imaging. The layers of the ASC were precisely identified in situ, in sections, in isolated dissected specimens and the same structures were correlated with their sonographic appearance. The results of the measurements of ASC components in this study on male cadavers were variable, suggesting that these should be used with caution in diagnostic and management settings. PMID:19486204

Laparoscopic versus open-component separation: a comparative analysis in a porcine model.

PubMed

Rosen, Michael J; Williams, Christina; Jin, Judy; McGee, Michael F; Schomisch, Steve; Marks, Jeffrey; Ponsky, Jeffrey

2007-09-01

The ideal surgical treatment for complicated ventral hernias remains elusive. Traditional component separation provides local advancement of native tissue for tension-free closure without prosthetic materials. This technique requires an extensive subcutaneous dissection with division of perforating vessels predisposing to skin-flap necrosis and complicated wound infections. A minimally invasive component separation may decrease wound complication rates; however, the adequacy of the myofascial advancement has not been studied. Five 25-kg pigs underwent bilateral laparoscopic component separation. A 10-mm incision was made lateral to the rectus abdominus muscle. The external oblique fascia was incised, and a dissecting balloon was inflated between the internal and external oblique muscles. Two additional ports were placed in the intermuscular space. The external oblique was incised from the costal margin to the inguinal ligament. The maximal abdominal wall advancement was recorded. A formal open-component separation was performed and maximal advancement 5 cm superior and 5 cm inferior to the umbilicus was recorded for comparison. Groups were compared using standard statistical analysis. The laparoscopic component separation was completed successfully in all animals, with a mean of 22 min/side. Laparoscopic component separation yielded 3.9 cm (SD 1.1) of fascial advancement above the umbilicus, whereas 4.4 cm (1.2) was obtained after open release (P = .24). Below the umbilicus, laparoscopic release achieved 5.0 cm (1.0) of advancement, whereas 5.8 cm (1.2) was gained after open release (P = .13). The minimally invasive component separation achieved an average of 86% of the myofascial advancement compared with a formal open release. The laparoscopic approach does not require extensive subcutaneous dissection and might theoretically result in a decreased incidence or decreased complexity of postoperative wound infections or skin-flap necrosis. Based on our preliminary data in this porcine model, further comparative studies of laparoscopic versus open component separation in complex ventral hernia repair is warranted to evaluate postoperative morbidity and long-term hernia recurrence rates.

Processes and procedures for a worldwide biological samples distribution; product assurance and logistic activities to support the mice drawer system tissue sharing event

NASA Astrophysics Data System (ADS)

Benassai, Mario; Cotronei, Vittorio

The Mice Drawer System (MDS) is a scientific payload developed by the Italian Space Agency (ASI), it hosted 6 mice on the International Space Station (ISS) and re-entered on ground on November 28, 2009 with the STS 129 at KSC. Linked to the MDS experiment, a Tissue Sharing Program (TSP), was developed in order to make available to 16 Payload Investigators (PI) (located in USA, Canada, EU -Italy, Belgium and Germany -and Japan) the biological samples coming from the mice. ALTEC SpA (a PPP owned by ASI, TAS-I and local institutions) was responsible to support the logistics aspects of the MDS samples for the first MDS mission, in the frame of Italian Space Agency (ASI) OSMA program (OSteoporosis and Muscle Atrophy). The TSP resulted in a complex scenario, as ASI, progressively, extended the original OSMA Team also to researchers from other ASI programs and from other Agencies (ESA, NASA, JAXA). The science coordination was performed by the University of Genova (UNIGE). ALTEC has managed all the logistic process with the support of a specialized freight forwarder agent during the whole shipping operation phases. ALTEC formalized all the steps from the handover of samples by the dissection Team to the packaging and shipping process in a dedicated procedure. ALTEC approached all the work in a structured way, performing: A study of the aspects connected to international shipments of biological samples. A coopera-tive work with UNIGE/ASI /PIs to identify all the needs of the various researchers and their compatibility. A complete revision and integration of shipment requirements (addresses, tem-peratures, samples, materials and so on). A complete definition of the final shipment scenario in terms of boxes, content, refrigerant and requirements. A formal approach to identification and selection of the most suited and specialized Freight Forwarder. A clear identification of all the processes from sample dissection by PI Team, sample processing, freezing, tube preparation, labeling, packaging, shipment and inspection at receiving sites, by introducing and using Forms and Procedures. A clear identification of Roles, by introducing a Board composed of NASA, ASI, PIs and ALTEC to drive and certify the critical points. Support to Team also for acces-sory aspects like badging or other kind of shipments. Support to meetings and teleconferences to cooperate in definition of mission scenario, that resulted also in the need of splitting the teams for KSC and Dryden. Support to dry run tests and meetings to tune the procedures and activities to the most refined detail. Support at both landing sites, with final shipment from KSC to all the final destination. Support data collection about status of the various incoming inspections at receiving sites. All the above mentioned activities will be detailed in the paper.

[Historical outline on the nomenclature of neck lymph nodes as a basis of neck dissection classification].

PubMed

Werner, J A

2001-07-01

The neck dissection classification is based considerably on the organization of the lymph nodes of the neck. Terminology and anatomical allocation of nearly 300 cervicofacial lymph nodes repeatedly changed since the beginning of the 20th century. Analysis of the literature on neck lymph node organization with reference to the development of the neck dissection classification. The first fundamental nomenclature of the neck lymph nodes is founded on the work of Rouviére (1932). Suárez (1963) described the functional neck dissection on the basis of the fascial compartmentalization of the neck. Lindberg (1972) left the predominantly anatomically correlated grouping of the cervical lymph nodes as described by Rouviére and divided the lymphatic system of the neck on basis of pathophysiological mechanisms. The attention regarding the location of occult metastases led to the description of the selective neck dissection. Since the fundamental work of Shah et al. (1981) there was a multiplicity of more or less slight changes of the neck node regions. These changes were again basis for new neck dissection terminologies. A new classification was introduced in the year 2000 as the revised version of the American Head and Neck Society. The revised version of the neck dissection classification can reduce former controversies, particularly regarding an optimized intraoperative allocation of the lymph nodes and a simplified terminology of the selective neck dissection. With the goal of a standardization of the neck dissection forms it remains to be seen if the proponents of the functional neck dissection after Suárez consider the extent of the neck dissection in patients with N0 neck in favor of the selective neck dissection.

Comparative Activity-Based Flavin-Dependent Oxidase Profiling.

PubMed

Krysiak, Joanna; Breinbauer, Rolf

2017-01-01

Activity-based protein profiling (ABPP) has become a powerful chemoproteomic technology allowing for the dissection of complex ligand-protein interactions in their native cellular environment. One of the biggest challenges for ABPP is the extension of the proteome coverage. In this chapter a new ABPP strategy dedicated to monoamine oxidases (MAO) is presented. These enzymes are representative examples of flavin-dependent oxidases, playing a crucial role in the regulation of nervous system signaling.

"And afterwards your body to be given for public dissection": a history of the murderers dissected in Glasgow and the west of Scotland.

PubMed

Kennedy, S S; McLeod, K J; McDonald, S W

2001-02-01

Between 1752 and 1832, the bodies of hanged murderers were dissected or gibbeted. During this period, 38 murderers were executed in the West of Scotland. The bodies of at least 23 were dissected in Glasgow. The stories of these murders are recounted. Insight is also given into the attitudes of the public and the anatomists to dissection of executed murderers.

The risk for type B aortic dissection in Marfan syndrome.

PubMed

den Hartog, Alexander W; Franken, Romy; Zwinderman, Aeilko H; Timmermans, Janneke; Scholte, Arthur J; van den Berg, Maarten P; de Waard, Vivian; Pals, Gerard; Mulder, Barbara J M; Groenink, Maarten

2015-01-27

Aortic dissections involving the descending aorta are a major clinical problem in patients with Marfan syndrome. The purpose of this study was to identify clinical parameters associated with type B aortic dissection and to develop a risk model to predict type B aortic dissection in patients with Marfan syndrome. Patients with the diagnosis of Marfan syndrome and magnetic resonance imaging or computed tomographic imaging of the aorta were followed for a median of 6 years for the occurrence of type B dissection or the combined end point of type B aortic dissection, distal aortic surgery, and death. A model using various clinical parameters as well as genotyping was developed to predict the risk for type B dissection in patients with Marfan syndrome. Between 1998 and 2013, 54 type B aortic dissections occurred in 600 patients with Marfan syndrome (mean age 36 ± 14 years, 52% male). Independent variables associated with type B aortic dissection were prior prophylactic aortic surgery (hazard ratio: 2.1; 95% confidence interval: 1.2 to 3.8; p = 0.010) and a proximal descending aorta diameter ≥27 mm (hazard ratio: 2.2; 95% confidence interval: 1.1 to 4.3; p = 0.020). In the risk model, the 10-year occurrence of type B aortic dissection in low-, moderate-, and high-risk patients was 6%, 19%, and 34%, respectively. Angiotensin II receptor blocker therapy was associated with fewer type B aortic dissections (hazard ratio: 0.3; 95% confidence interval: 0.1 to 0.9; p = 0.030). Patients with Marfan syndrome with prior prophylactic aortic surgery are at substantial risk for type B aortic dissection, even when the descending aorta is only slightly dilated. Angiotensin II receptor blocker therapy may be protective in the prevention of type B aortic dissections. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Problems of Dissection.

ERIC Educational Resources Information Center

Davis, Pat

1997-01-01

Describes some problems of classroom dissection including the cruelty that animals destined for the laboratory suffer. Discusses the multilevel approach that the National Anti-Vivisection Society (NAVS) has developed to address the problems of animal dissection such as offering a dissection hotline, exhibiting at science teacher conferences, and…

Sequential segmental terminal lenticular side-cut dissection for safe and effective small-incision lenticule extraction in thin lenticules.

PubMed

Jacob, Soosan; Agarwal, Amar; Mazzotta, Cosimo; Agarwal, Athiya; Raj, John Michael

2017-04-01

Small-incision lenticule extraction may be associated with complications such as partial lenticular dissection, torn lenticule, lenticular adherence to cap, torn cap, and sub-cap epithelial ingrowth, some of which are more likely to occur during low-myopia corrections. We describe sequential segmental terminal lenticular side-cut dissection to facilitate minimally traumatic and smooth lenticular extraction. Anterior lamellar dissection is followed by central posterior lamellar dissection, leaving a thin peripheral rim and avoiding the lenticular side cut. This is followed by sequential segmental dissection of the lenticular side cut in a manner that fixates the lenticule and provides sufficient resistance for smooth and complete dissection of the posterior lamellar cut without undesired movements of the lenticule. The technique is advantageous in thin lenticules, where the risk for complications is high, but can also be used in thick lenticular dissection using wider sweeps to separate the lenticular side cut sequentially. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.