Automatic Categorization and Scoring of Solid, Part-Solid and Non-Solid Pulmonary Nodules in CT Images with Convolutional Neural Network.

Sci Rep. 2017 Sep 01;7(1):8533

Authors: Tu X, Xie M, Gao J, Ma Z, Chen D, Wang Q, Finlayson SG, Ou Y, Cheng JZ

Abstract
We present a computer-aided diagnosis system (CADx) for the automatic categorization of solid, part-solid and non-solid nodules in pulmonary computerized tomography images using a Convolutional Neural Network (CNN). Provided with only a two-dimensional region of interest (ROI) surrounding each nodule, our CNN automatically reasons from image context to discover informative computational features. As a result, no image segmentation processing is needed for further analysis of nodule attenuation, allowing our system to avoid potential errors caused by inaccurate image processing. We implemented two computerized texture analysis schemes, classification and regression, to automatically categorize solid, part-solid and non-solid nodules in CT scans, with hierarchical features in each case learned directly by the CNN model. To show the effectiveness of our CNN-based CADx, an established method based on histogram analysis (HIST) was implemented for comparison. The experimental results show significant performance improvement by the CNN model over HIST in both classification and regression tasks, yielding nodule classification and rating performance concordant with those of practicing radiologists. Adoption of CNN-based CADx systems may reduce the inter-observer variation among screening radiologists and provide a quantitative reference for further nodule analysis.

PMID: 28864824 [PubMed - in process]

Research and Discovery Science and the Future of Dental Education and Practice.

J Dent Educ. 2017 Sep;81(9):eS97-eS107

Authors: Polverini PJ, Krebsbach PH

Abstract
Dental graduates of 2040 will face new and complex challenges. If they are to meet these challenges, dental schools must develop a research and discovery mission that will equip graduates with the new knowledge required to function in a modern health care environment. The dental practitioner of 2040 will place greater emphasis on risk assessment, disease prevention, and health maintenance; and the emerging discipline of precision medicine and systems biology will revolutionize disease diagnosis and reveal new targeted therapies. The dental graduate of 2040 will be expected to function effectively in a collaborative, learning health care system and to understand the impact of health care policy on local, national, and global communities. Emerging scientific fields such as big data analytics, stem cell biology, tissue engineering, and advanced biomimetics will impact dental practice. Despite all the warning signs indicating how the changing scientific and heath care landscape will dramatically alter dental education and dental practice, dental schools have yet to reconsider their research and educational priorities and clinical practice objectives. Until dental schools and the practicing community come to grips with these challenges, this persistent attitude of complacency will likely be at the dental profession's peril. This article was written as part of the project "Advancing Dental Education in the 21(st) Century."

PMID: 28864810 [PubMed - in process]

Metabolomics in Yeast.

Cold Spring Harb Protoc. 2017 Sep 01;2017(9):pdb.top083576

Authors: Caudy AA, Mülleder M, Ralser M

Abstract
Budding yeast has from the beginning been a major eukaryotic model for the study of metabolic network structure and function. This is attributable to both its genetic and biochemical capacities and its role as a workhorse in food production and biotechnology. New inventions in analytical technologies allow accurate, simultaneous detection and quantification of metabolites, and a series of recent findings have placed the metabolic network at center stage in the physiology of the cell. For example, metabolism might have facilitated the origin of life, and in modern organisms it not only provides nutrients to the cell but also serves as a buffer to changes in the cellular environment, a regulator of cellular processes, and a requirement for cell growth. These findings have triggered a rapid and massive renaissance in this important field. Here, we provide an introduction to analysis of metabolomics in yeast.

PMID: 28864573 [PubMed - in process]

A High-Throughput Method for the Quantitative Determination of Free Amino Acids in Saccharomyces cerevisiae by Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry.

Cold Spring Harb Protoc. 2017 Sep 01;2017(9):pdb.prot089094

Authors: Mülleder M, Bluemlein K, Ralser M

Abstract
Amino acids are the building blocks for protein synthesis and the precursors for many biomolecules, such as glutathione and S-adenosylmethionine. Their intracellular concentrations provide valuable information about the overall metabolic state of the cell, as they are closely connected to carbon and nitrogen metabolism and are tightly regulated to meet cellular demands in ever-changing environments. Here, we describe a fast and simple method enabling metabolic profiling for free amino acids for large numbers of yeast strains. Metabolites are extracted with boiling ethanol and, without further conditioning, analyzed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS). Several hundred samples can be prepared in a single day with an analytical runtime of 3.25 min. This method is valuable for functional characterization, identification of metabolic regulators and processes, or monitoring of biotechnological processes.

PMID: 28864565 [PubMed - in process]

Induced parental care in a poison frog: a tadpole cross-fostering experiment.

J Exp Biol. 2017 Sep 01;:

Authors: Pašukonis A, Beck KB, Fischer MT, Weinlein S, Stückler S, Ringler E

Abstract
Understanding the external stimuli and natural contexts that elicit complex behaviors, such as parental care, is key in linking behavioral mechanisms to their real-life function. Poison frogs provide obligate parental care by shuttling their tadpoles from terrestrial clutches to aquatic nurseries, but little is known about the proximate mechanisms that control these behaviors. In this study, we used Allobates femoralis, a poison frog with predominantly male parental care, to investigate whether tadpole transport can be induced in both sexes by transferring unrelated tadpoles to the backs of adults in the field. Specifically, we asked if the presence of tadpoles on an adult's back can override the decision-making rules preceding tadpole pick-up and induce the recall of spatial memory necessary for finding tadpole deposition sites. We used telemetry to facilitate accurate tracking of individual frogs and spatial analyses to compare movement trajectories. All tested individuals transported their foster-tadpoles to water pools outside their home area. Contrary to our expectation, we found no sex difference in the likelihood to transport nor in the spatial accuracy of finding tadpole deposition sites. We reveal that a stereotypical cascade of parental behaviors that naturally involves sex-specific offspring recognition strategies and the use of spatial memory can be manipulated by experimental placement of unrelated tadpoles on adult frogs. As individuals remained inside their home area when only the jelly from tadpole-containing clutches was brushed on the back, we speculate that tactile rather than chemical stimuli are triggering these parental behaviors.

PMID: 28864563 [PubMed - as supplied by publisher]

The core transcriptome of mammalian placentas and the divergence of expression with placental shape.

Placenta. 2017 Sep;57:71-78

Authors: Armstrong DL, McGowen MR, Weckle A, Pantham P, Caravas J, Agnew D, Benirschke K, Savage-Rumbaugh S, Nevo E, Kim CJ, Wagner GP, Romero R, Wildman DE

Abstract
INTRODUCTION: The placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved.
METHOD: Using RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades.
RESULTS: We identified a set of 115 core genes which is expressed (FPKM ≥10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1). We also identified multiple pre-eclampsia associated genes which are differentially expressed in Homo sapiens when compared to the other 13 species. Multiple genes are significantly associated with placenta morphology, including EREG and WNT5A which are both associated with placental shape.
DISCUSSION: 115 genes are important for the core functions of the placenta in all eutherian species analyzed. The molecular functions and pathways enriched in the core placenta align with the evolutionarily conserved functionality of the placenta.

PMID: 28864021 [PubMed - in process]

56 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/09/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

56 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/09/02

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Rapid Flow Cytometry Detection of a Single Viable Escherichia coli O157:H7 Cell in Raw Spinach Using a Simplified Sample Preparation Technique.

Front Microbiol. 2017;8:1493

Authors: Williams AJ, Cooper WM, Ramsaroop S, Alusta P, Buzatu DA, Wilkes JG

Abstract
Very low cell count detection of Escherichia coli O157:H7 in foods is critical, since an infective dose for this pathogen may be only 10 cells, and fewer still for vulnerable populations. A flow cytometer is able to detect and count individual cells of a target bacterium, in this case E. coli O157:H7. The challenge is to find the single cell in a complex matrix like raw spinach. To find that cell requires growing it as quickly as possible to a number sufficiently in excess of matrix background that identification is certain. The experimental design for this work was that of a U.S. Food and Drug Administration (FDA) In-House Level 3 validation executed in the technology's originating laboratory. Using non-selective enrichment broth, 6.5 h incubation at 42°C, centrifugation for target cell concentration, and a highly selective E. coli O157 fluorescent antibody tag, the cytometry method proved more sensitive than a reference regulatory method (p = 0.01) for detecting a single target cell, one E. coli O157:H7 cell, in 25 g of spinach. It counted that cell's daughters with at least 38× signal-to-noise ratio, analyzing 25 samples in total-time-to-results of 9 h.

PMID: 28855894 [PubMed]

25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/09/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Ultra-rare mutations in SRCAP segregate in Caribbean Hispanic families with Alzheimer disease.

Neurol Genet. 2017 Oct;3(5):e178

Authors: Vardarajan BN, Tosto G, Lefort R, Yu L, Bennett DA, De Jager PL, Barral S, Reyes-Dumeyer D, Nagy PL, Lee JH, Cheng R, Medrano M, Lantigua R, Rogaeva E, St George-Hyslop P, Mayeux R

Abstract
OBJECTIVE: To identify rare coding variants segregating with late-onset Alzheimer disease (LOAD) in Caribbean Hispanic families.
METHODS: Whole-exome sequencing (WES) was completed in 110 individuals from 31 Caribbean Hispanic families without APOE ε4 homozygous carriers. Rare coding mutations segregating in families were subsequently genotyped in additional families and in an independent cohort of Caribbean Hispanic patients and controls. SRCAP messenger RNA (mRNA) expression was assessed in whole blood from mutation carriers with LOAD, noncarriers with LOAD, and healthy elderly controls, and also from autopsied brains in 2 clinical neuropathologic cohort studies of aging and dementia.
RESULTS: Ten ultra-rare missense mutations in the Snf2-related CREBBP, activator protein (SRCAP), were found in 12 unrelated families. Compared with the frequency in Caribbean Hispanic controls and the Latino population in the Exome Aggregation Consortium, the frequency of SRCAP mutations among Caribbean Hispanic patients with LOAD was significantly enriched (p = 1.19e-16). mRNA expression of SRCAP in whole blood was significantly lower in mutation carriers with LOAD, while the expression in whole blood and in the brain was significantly higher in nonmutation carriers with LOAD. Brain expression also correlated with clinical and neuropathologic endophenotypes.
CONCLUSIONS: WES in Caribbean Hispanic families with LOAD revealed ultra-rare missense mutations in SRCAP, a gene expressed in the brain and mutated in Floating-Harbor syndrome. SRCAP is a potent coactivator of the CREB-binding protein and a regulator of DNA damage response involving ATP-dependent chromatin remodeling. We hypothesize that increased expression in LOAD suggests a compensatory mechanism altered in mutation carriers.

PMID: 28852706 [PubMed]

33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Molecular signatures of differential responses to exercise trainings during rehabilitation.

Biomed Genet Genom. 2017;2(1):

Authors: Chen YW, Gregory C, Ye F, Harafuji N, Lott D, Lai SH, Mathur S, Scarborough M, Gibbs P, Baligand C, Vandenborne K

Abstract
The loss and recovery of muscle mass and function following injury and during rehabilitation varies among individuals. While recent expression profiling studies have illustrated transcriptomic responses to muscle disuse and remodeling, how these changes contribute to the physiological responses are not clear. In this study, we quantified the effects of immobilization and subsequent rehabilitation training on muscle size and identified molecular pathways associated with muscle responsiveness in an orthopaedic patient cohort study. The injured leg of 16 individuals with ankle injury was immobilized for a minimum of 4 weeks, followed by a 6-week rehabilitation program. The maximal cross-sectional area (CSA) of the medial gastrocnemius muscle of the immobilized and control legs were determined by T1-weighted axial MRI images. Genome-wide mRNA profiling data were used to identify molecular signatures that distinguish the patients who responded to immobilization and rehabilitation and those who were considered minimal responders.
RESULTS: Using 6% change as the threshold to define responsiveness, a greater degree of changes in muscle size was noted in high responders (-14.9 ± 3.6%) compared to low responders (0.1 ± 0.0%) during immobilization. In addition, a greater degree of changes in muscle size was observed in high responders (20.5 ± 3.2%) compared to low responders (2.5 ± 0.9%) at 6-week rehabilitation. Microarray analysis showed a higher number of genes differentially expressed in the responders compared to low responders in general; with more expression changes observed at the acute stage of rehabilitation in both groups. Pathways analysis revealed top molecular pathways differentially affected in the groups, including genes involved in mitochondrial function, protein turn over, integrin signaling and inflammation. This study confirmed the extent of muscle atrophy due to immobilization and recovery by exercise training is associated with distinct remodeling signature, which can potentially be used for evaluating and predicting clinical outcomes.

PMID: 28845464 [PubMed]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Genomic regulation of type 2 diabetes endophenotypes: Contribution from genetic studies in the Goto-Kakizaki rat.

Biochimie. 2017 Aug 23;:

Authors: Bihoreau MT, Dumas ME, Lathrop M, Gauguier D

Abstract
The inbred Goto-Kakizaki (GK) rat strain is a unique model of spontaneous type 2 diabetes mellitus caused by naturally occurring genetic variants that have been selectively isolated from an outbred colony of Wistar rats. Genetic and genomic studies that we designed with Alain Ktorza in experimental crosses and congenic strains of the GK have shed light on the complex etiopathogenesis of diabetes phenotypes in this model. Diabetes-related phenotypes in the GK are under polygenic control and distinct genetic loci regulate glucose tolerance, insulin secretion, β-cell mass and plasma lipids. Metabolome and transcriptome profiling data in GK crosses and congenics, combined with GK genome resequencing, have resulted in a comprehensive landscape of genomic regulations of metabolism that can disentangle causal relationships between GK variants and diabetes phenotypes. Application of systems biology and systems genetics in the GK has contributed to improve our understanding of the fundamental mechanisms regulating metabolism. The wealth of physiological, genetic and genomic information in this strain makes it one of the most powerful model systems to improve our understanding of genetic regulations of metabolism and for testing therapeutic solutions for diabetes.

PMID: 28843612 [PubMed - as supplied by publisher]

Cell-Cycle Position of Single MYC-Driven Cancer Cells Dictates Their Susceptibility to a Chemotherapeutic Drug.

Cell Syst. 2017 Aug 23;:

Authors: Ryl T, Kuchen EE, Bell E, Shao C, Flórez AF, Mönke G, Gogolin S, Friedrich M, Lamprecht F, Westermann F, Höfer T

Abstract
While many tumors initially respond to chemotherapy, regrowth of surviving cells compromises treatment efficacy in the long term. The cell-biological basis of this regrowth is not understood. Here, we characterize the response of individual, patient-derived neuroblastoma cells driven by the prominent oncogene MYC to the first-line chemotherapy, doxorubicin. Combining live-cell imaging, cell-cycle-resolved transcriptomics, and mathematical modeling, we demonstrate that a cell's treatment response is dictated by its expression level of MYC and its cell-cycle position prior to treatment. All low-MYC cells enter therapy-induced senescence. High-MYC cells, by contrast, disable their cell-cycle checkpoints, forcing renewed proliferation despite treatment-induced DNA damage. After treatment, the viability of high-MYC cells depends on their cell-cycle position during treatment: newborn cells promptly halt in G1 phase, repair DNA damage, and form re-growing clones; all other cells show protracted DNA repair and ultimately die. These findings demonstrate that fast-proliferating tumor cells may resist cytotoxic treatment non-genetically, by arresting within a favorable window of the cell cycle.

PMID: 28843484 [PubMed - as supplied by publisher]

Guidelines for Developing Successful Short Advanced Courses in Systems Medicine and Systems Biology.

Cell Syst. 2017 Aug 23;:

Authors: Gomez-Cabrero D, Marabita F, Tarazona S, Cano I, Roca J, Conesa A, Sabatier P, Tegnér J

Abstract
Systems medicine and systems biology have inherent educational challenges. These have largely been addressed either by providing new masters programs or by redesigning undergraduate programs. In contrast, short courses can respond to a different need: they can provide condensed updates for professionals across academia, the clinic, and industry. These courses have received less attention. Here, we share our experiences in developing and providing such courses to current and future leaders in systems biology and systems medicine. We present guidelines for how to reproduce our courses, and we offer suggestions for how to select students who will nurture an interdisciplinary learning environment and thrive there.

PMID: 28843483 [PubMed - as supplied by publisher]

Single-tubule RNA-Seq uncovers signaling mechanisms that defend against hyponatremia in SIADH.

Kidney Int. 2017 Aug 23;:

Authors: Lee JW, Alsady M, Chou CL, de Groot T, Deen PMT, Knepper MA, Ecelbarger CM

Abstract
In the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatremia is limited by onset of vasopressin-escape caused by loss of the water channel aquaporin-2 in the renal collecting duct despite high circulating vasopressin. Here, we use the methods of systems biology in a well-established rat model of SIADH to identify signaling pathways activated at the onset of vasopressin-escape. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts of vasopressin-treated rats at 1, 2, and 4 days after initiation of oral water loading in comparison to time-control rats without water loading. The time-dependent mRNA abundance changes were mapped to gene sets associated with curated canonical signaling pathways and revealed evidence of perturbation of transforming growth factor β signaling and epithelial-to-mesenchymal transition on Day 1 of water loading simultaneous with the initial fall in Aqp2 gene expression. On Day 2 of water loading, transcriptomic changes mapped to Notch signaling and the transition from G0 into the cell cycle but arrest at the G2/M stage. There was no evidence of cell proliferation or altered principal or intercalated cell numbers. Exposure of vasopressin-treated cultured mpkCCD cells to transforming growth factor β resulted in a virtually complete loss of aquaporin-2. Thus, there is a partial epithelial-to-mesenchymal transition during vasopressin escape with a subsequent shift from quiescence into the cell cycle with eventual arrest and loss of aquaporin-2.

PMID: 28843412 [PubMed - as supplied by publisher]

Systems and synthetic biology for the biotechnological application of cyanobacteria.

Curr Opin Biotechnol. 2017 Aug 23;49:94-99

Authors: Hagemann M, Hess WR

Abstract
Cyanobacteria are the only prokaryotes that perform oxygenic photosynthesis. Their evolutionary relation to plastids in eukaryotic phototrophs and their increasing utilization as green cell factories initiated the use of systems biology approaches early on. For select model strains, extensive 'omics' data sets have been generated, and genome-wide models have been elucidated. Moreover, the results obtained may be used for the optimization of cyanobacterial metabolism, which can direct the biotechnological production of biofuels or chemical feedstock. Synthetic biology approaches permit the rational construction of novel metabolic pathways that are based on the combination of multiple enzymatic activities of different origins. In addition, the manipulation of whole metabolic networks by CRISPR-based and sRNA-based technologies with multiple parallel targets will further stimulate the use of cyanobacteria for diverse applications in basic research and biotechnology.

PMID: 28843192 [PubMed - as supplied by publisher]

Distinct metabolomic signature in cerebrospinal fluid in early parkinson's disease.

Mov Disord. 2017 Aug 26;:

Authors: Trezzi JP, Galozzi S, Jaeger C, Barkovits K, Brockmann K, Maetzler W, Berg D, Marcus K, Betsou F, Hiller K, Mollenhauer B

Abstract
OBJECTIVE: The purpose of this study was to profile cerebrospinal fluid (CSF) from early-stage PD patients for disease-related metabolic changes and to determine a robust biomarker signature for early-stage PD diagnosis.
METHODS: By applying a non-targeted and mass spectrometry-driven approach, we investigated the CSF metabolome of 44 early-stage sporadic PD patients yet without treatment (DeNoPa cohort). We compared all detected metabolite levels with those measured in CSF of 43 age- and gender-matched healthy controls. After this analysis, we validated the results in an independent PD study cohort (Tübingen cohort).
RESULTS: We identified that dehydroascorbic acid levels were significantly lower and fructose, mannose, and threonic acid levels were significantly higher (P < .05) in PD patients when compared with healthy controls. These changes reflect pathological oxidative stress responses, as well as protein glycation/glycosylation reactions in PD. Using a machine learning approach based on logistic regression, we successfully predicted the origin (PD patients vs healthy controls) in a second (n = 18) as well as in a third and completely independent validation set (n = 36). The biomarker signature is composed of the three markers-mannose, threonic acid, and fructose-and allows for sample classification with a sensitivity of 0.790 and a specificity of 0.800.
CONCLUSION: We identified PD-specific metabolic changes in CSF that were associated with antioxidative stress response, glycation, and inflammation. Our results disentangle the complexity of the CSF metabolome to unravel metabolome changes related to early-stage PD. The detected biomarkers help understanding PD pathogenesis and can be applied as biomarkers to increase clinical diagnosis accuracy and patient care in early-stage PD. © 2017 International Parkinson and Movement Disorder Society.

PMID: 28843022 [PubMed - as supplied by publisher]