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Abstract Modeling and sensor innovations in the last decade have enabled routine and continuous estimation of daily gross primary productivity (GPP) for rivers. Here, we generate and evaluate within and across year variability for 59 US rivers for which we have compiled a 14‐yr time series of daily GPP estimates. River productivity varied widely across (median annual GPP 462 g C m−2 yr−1, range 19–3445 g C m−2 yr−1) and within rivers (CVGPP‐Inter 5.7–37.3%). Within this dataset, we found that five rivers have become consistently more productive over time, while 11 rivers have become consistently less productive. Furthermore, trends in ecosystem phenology were identified, where cumulative annual GPP was reached earlier (n = 3) and later (n = 13) in the year across the 25th, 50th, 75th, and 95th percentiles. Understanding the drivers of productivity trends in rivers will elucidate patterns in river food webs and the functional role of river biogeochemistry.

In the realm of psychology and related fields, like school psychology, obtaining informed consent from clients or participants who are 18 years old or older is mandatory for researchers. However, if the individuals are below 18 years old or under a conservatorship, their assent is crucial even if their parent or legal guardian has provided formal consent. Despite the widespread recognition of the importance of assent during research, there is a lack of research and guidelines on how to obtain it effectively. To bridge this gap, we conducted a review and created a summary of research published in school psychology journals on gaining assent during research studies. The articles were categorized based on the experimental design, population, and level of assent described. Our findings offer a comprehensive overview of the current state of research on gaining assent in school psychology, which will enhance transparency in research methods.

Purpose: Nearly 20% of U.S. Americans report a hearing loss, yet our current health care system is poorly designed and equipped to effectively care for these individuals. Individuals with hearing loss report communication breakdowns, inaccessible health information, reduced awareness and training by health care providers, and decreased satisfaction while struggling with inadequate health literacy. These all contribute to health inequities and increased health care expenditures and inefficiencies. It is time to reframe the health care system for these individuals using existing models of best practices and accessibility to mitigate inequities and improve quality of care. Method: A review of system-, clinic-, provider-, and patient-level barriers, along with existing and suggested efforts to improve care for individuals with hearing loss, are presented. Results: These strategies include improving screening and identification of hearing loss, adopting universal design and inclusion principles, implementing effective communication approaches, leveraging assistive technologies and training, and diversifying a team to better care for patients with hearing loss. Patients should also be encouraged to seek social support and resources from hearing loss organizations while leveraging technologies to help facilitate communication. Conclusions: The strategies described introduce actionable steps that can be made at the system, clinic, provider, and patient levels. With implementation of these steps, significant progress can be made to more proactively meet the needs of patients with hearing loss.

Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC. Methods: We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected. Results: Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%). Conclusions: Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated.

Ryan D Castle,1 Michelle A Williams,2 William C Bushell,3 J Adam Rindfleisch,4 Christine Tara Peterson,5 James Marzolf,6 Kimberly Brouwer,7 Paul J Mills8 1Science Division, Whole Health Institute, Bentonville, AR, USA; 2Harvard T.H. Chan School of Public Health, Department of Global Health and Population, Harvard University, Boston, MA, USA; 3Science Division, Whole Health Institute, New York, NY, USA; 4Education Department, Whole Health School of Medicine and Health Sciences, Bentonville, AR, USA; 5Center of Excellence for Research and Training in Integrative Health, Department of Family Medicine, School of Medicine, University of California, San Diego, CA, USA; 6Health Sector Finance & Policy, Whole Health Institute, Bentonville, AR, USA; 7Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA, USA; 8Herbert Wertheim School of Public Health and Human Longevity Science, Center of Excellence for Research and Training in Integrative Health, University of California, San Diego, CA, USACorrespondence: Ryan D CastleScience Division, Whole Health Institute, 900 McClain Road, Bentonville, AR, 72712, USAEmail rcastle@wholehealth.orgIntroduction: COVID-19 poses a chronic threat to inflammatory systems, reinforcing the need for efficient anti-inflammatory strategies. The purpose of this review and analysis was to determine the efficacy of various interventions upon the inflammatory markers most affected by COVID-19. The focus was on the markers associated with COVID-19, not the etiology of the virus itself.Methods: Based on 27 reviewed papers, information was extracted on the effects of COVID-19 upon inflammatory markers, then the effects of standard treatments (Remdesivir, Tocilizumab) and adjunctive interventions (vitamin D3, melatonin, and meditation) were extracted for those markers. These data were used to approximate effect sizes for the disease or interventions via standardized mean differences (SMD).Results: The data that were available indicated that adjunctive interventions affected 68.4% of the inflammatory markers impacted by COVID-19, while standard pharmaceutical medication affected 26.3%.Discussion: Nonstandard adjunctive care appeared to have comparable or superior effects in comparison to Remdesivir and Tocilizumab on the inflammatory markers most impacted by COVID-19. Alongside standards of care, melatonin, vitamin D3, and meditation should be considered for treatment of SARS-COV-2 infection and COVID-19 disease.Keywords: COVID-19, inflammation, cytokine storm, effect size, antivirals, corticosteroids, melatonin, vitamin D, meditation, whole health

Abstract Disturbances can alter the structure and function of ecosystems. In stream ecosystems, changes in discharge and physicochemistry at short, intermediate, and long recurrence intervals can affect food webs and ecosystem processes. In this paper, we compare pH regimes in streams at La Selva Biological Station, Costa Rica, where episodic acidification frequency across the stream network varies widely due to buffering from inputs of bicarbonate‐rich interbasin groundwater. To examine the effects of acidification on ecosystem structure and function, we experimentally increased the buffering capacity of a headwater stream reach and compared it to an unbuffered upstream reach. We compared these reaches to a naturally buffered and unbuffered reaches of a second headwater stream. We quantified ecosystem structural (macroinvertebrate assemblages on leaf litter and coarse woody debris) and functional responses (leaf litter and coarse woody debris decomposition rates, and growth rates of a focal insect taxon [Diptera: Chironomidae]). Non‐metric multidimensional scaling and analysis of similarity revealed that macroinvertebrate assemblages were relatively homogenous across the four study reaches, although the naturally buffered reach was the most dissimilar. Ecosystem function, as measured by chironomid growth rates, was greater in the naturally buffered reach, while decomposition rates did not differ across the four reaches. Our results indicate that biological assemblages are adapted to pH regimes of frequently acidified stream reaches. Our experiment informs the effects on structure and function at short time scales in streams that experience moderate acidification, but larger magnitude acidification events in response to hydroclimatic change, as projected under climate change scenarios, may induce stronger responses in streams.

Abstract The increasing availability of high‐frequency freshwater ecosystem metabolism data provides an opportunity to identify links between metabolic regimes, as gross primary production and ecosystem respiration patterns, and consumer energetics with the potential to improve our current understanding of consumer dynamics (e.g., population dynamics, community structure, trophic interactions). We describe a conceptual framework linking metabolic regimes of flowing waters with consumer community dynamics. We use this framework to identify three emerging research needs: (1) quantifying the linkage of metabolism and consumer production data via food web theory and carbon use efficiencies, (2) evaluating the roles of metabolic dynamics and other environmental regimes (e.g., hydrology, light) in consumer dynamics, and (3) determining the degree to which metabolic regimes influence the evolution of consumer traits and phenology. Addressing these needs will improve the understanding of consumer biomass and production patterns as metabolic regimes can be viewed as an emergent property of food webs.

Background. Hypertrophic cardiomyopathy (HCM) in pediatric solid organ transplant recipients has been reported in association with use of calcineurin inhibitors. However, data on the incidence and prevalence of HCM in adult posttransplant patients are limited. We sought to describe the clinical characteristics of solid organ transplant recipients who were diagnosed with HCM from 2011 to 2021 at a single center. Methods. Patients who had undergone solid organ transplant and exhibited left ventricular hypertrophy with left ventricular wall thickness ≥13 mm on transthoracic echocardiography were included. Clinical history, pedigree analysis, clinical genetic testing, transthoracic echocardiography, cardiac magnetic resonance imaging, treatment, and follow-up testing results were collected. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges and compared using the Wilcoxon rank-sum and Kruskal-Wallis tests. A 2-sided P < 0.05 was considered statistically significant. Results. Three lung, 5 kidney, and 4 liver transplant recipients from 12 different families were included. Seven patients (58%) did not carry a preexisting diagnosis of hypertension, and none had a history of aortic or subaortic stenosis. A majority of patients exhibited asymmetric septal hypertrophy (67%; medial septal thickness versus left ventricular posterior wall thickness 17 versus 13 mm; P < 0.001) and dynamic left ventricular outflow tract (LVOT) obstruction (58%). All patients were managed long term with calcineurin inhibitors. Clinical genetic testing in 6 patients identified 2 with disease-causing variants in 2 sarcomere genes, myosin binding protein-C and myosin heavy chain 7. Four patients (33%) underwent successful septal reduction therapy for treatment of symptomatic LVOT obstruction. Conclusions. Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients, and genetic testing can identify individuals with sarcomeric HCM. Medical management and septal reduction therapies are treatment options for severe symptomatic disease.

Background Current payment models in the U.S. healthcare system are neither sustainable nor desirable. Expenses outpace revenue for most healthcare providers, while patients experience rising prices contrasted with inadequate health outcomes. Objective There is not a single, small adjustment that can remedy these issues; systemic problems require systemic solutions. One such solution involves whole-person care, an approach that emphasizes using diverse healthcare resources to align care with a patient’s values and goals as well as treat a patient’s physical, behavioral, emotional, and social risk factors. Methods In order to be most effective, whole-person care must be paired with a viable payment system that prioritizes positive outcomes and efficiency. The predominant fee-for-service payment system is not conducive to whole-person strategies. Results This paper examines the role of capitated payments, risk adjustments, social and structural determinants of health, and expense trends in an interdependent approach to healthcare industry system reform. Conclusion The Whole Health paradigm is optimized to improve both the financial performance of healthcare providers and the healthcare results of patients. Phased implementation is both feasible and sustainable.

Abstract Background Large numbers of post-deployment U.S. veterans are diagnosed with post-traumatic stress disorder (PTSD) and/or traumatic brain injury (TBI), leading to an urgent need for effective interventions to reduce symptoms and increase veterans’ coping. PTSD includes anxiety, flashbacks, and emotional numbing. The symptoms increase health care costs for stress-related illnesses and can make veterans’ civilian life difficult. Methods We used a randomized wait-list controlled design with repeated measures of U.S. military veterans to address our specific aim to test the efficacy of a 6-week therapeutic horseback riding (THR) program for decreasing PTSD symptoms and increasing coping self-efficacy, emotion regulation, social and emotional loneliness. Fifty-seven participants were recruited and 29 enrolled in the randomized trial. They were randomly assigned to either the horse riding group (n = 15) or a wait-list control group (n = 14). The wait-list control group experienced a 6-week waiting period, while the horse riding group began THR. The wait-list control group began riding after 6 weeks of participating in the control group. Demographic and health history information was obtained from all the participants. PTSD symptoms were measured using the standardized PTSD Checklist-Military Version (PCL-M). The PCL-M as well as other instruments including, The Coping Self Efficacy Scale (CSES), The Difficulties in Emotion Regulation Scale (DERS) and The Social and Emotional Loneliness Scale for Adults-short version (SELSA) were used to access different aspects of individual well-being and the PTSD symptoms. Results Participants had a statistically significant decrease in PTSD scores after 3 weeks of THR (P ≤ 0.01) as well as a statistically and clinically significant decrease after 6 weeks of THR (P ≤ 0.01). Logistic regression showed that participants had a 66.7% likelihood of having lower PTSD scores at 3 weeks and 87.5% likelihood at 6 weeks. Under the generalized linear model(GLM), our ANOVA findings for the coping self-efficacy, emotion regulation, and social and emotional loneliness did not reach statistical significance. The results for coping self-efficacy and emotion regulation trended in the predicted direction. Results for emotional loneliness were opposite the predicted direction. Logistic regression provided validation that outcome effects were caused by riding longer. Conclusion The findings suggest that THR may be a clinically effective intervention for alleviating PTSD symptoms in military veterans.

Despite the knowledge of complex prokaryotic-transcription mechanisms, generalized rules, such as the simplified organization of genes into operons with well-defined promoters and terminators, have had a significant role in systems analysis of regulatory logic in both bacteria and archaea. Here, we have investigated the prevalence of alternate regulatory mechanisms through genome-wide characterization of transcript structures of approximately 64% of all genes, including putative non-coding RNAs in Halobacterium salinarum NRC-1. Our integrative analysis of transcriptome dynamics and protein-DNA interaction data sets showed widespread environment-dependent modulation of operon architectures, transcription initiation and termination inside coding sequences, and extensive overlap in 3' ends of transcripts for many convergently transcribed genes. A significant fraction of these alternate transcriptional events correlate to binding locations of 11 transcription factors and regulators (TFs) inside operons and annotated genes-events usually considered spurious or non-functional. Using experimental validation, we illustrate the prevalence of overlapping genomic signals in archaeal transcription, casting doubt on the general perception of rigid boundaries between coding sequences and regulatory elements.

Review of: Jack P. Cunningham and Mark Hocknull (eds.), Robert Grosseteste and the Pursuit of Religious and Scientific Learning in the Middle Ages, (Studies in the History of Philosophy of Mind, 18), Switzerland: Springer, 2016, 401 pp., ISBN 978-3-319-33468-0 (hbk), 978-3-319-33466-4 (e-book)

Lamin A/C cardiac disease is a genetic cardiomyopathy and arrhythmia syndrome caused by alterations in the function of the nuclear lamin A and C proteins. It is inherited in an autosomal dominant manner and usually presents in mid- to late adulthood with atrioventricular conduction abnormalities, atrial and ventricular arrhythmias, biventricular dysfunction, and advanced heart failure. While rare, women of childbearing age can exhibit an aggressive disease course, and appropriate risk stratification and management are critical. Here, we present a case of newly diagnosed lamin A/C cardiac disease in a pregnant woman.

Review of: Ian C. Levy, Rita George-Tvrtković, Donald F. Duclow (eds.), Nicholas of Cusa and Islam. Polemic and Dialogue in the Late Middle Ages, (Studies in Medieval and Reformation Traditions, 183), Leiden – Boston: Brill, 2014. 251 pp. ISBN 9789004274761 (HBK)

En este artículo analizamos las tensiones y las contradicciones que atraviesanel intento de llevar a las instituciones políticas el movimiento de los indignados.Mediante una etnografía y observación participante en Madrid, Málaga yCórdoba alrededor del 15M (desde 2011) y Podemos (desde 2014) el artículoanaliza las tensiones que atraviesan el intento de llevar a las instituciones políticasel movimiento de los indignados. Mostramos que estas tensiones se comprendena partir del lugar y el sentido que tenía el consenso en el movimientode los indignados, que fueron parcialmente ocultados por las críticas a la faltade eficacia del movimiento y su rechazo a adoptar una estrategia política basadaen la representación institucional. A través del consenso, el 15M se revela, pordebajo del concepto de Multitud al que fue primariamente asociado, como elimaginario irrepresentable de una sociedad de iguales. Si entendemos el consensocomo la clave de la significación política del movimiento, nos preguntamoscómo la traducción hegemónica del movimiento propuesta por Podemos pudoreclamarse desde dicho imaginario.

Efficient nanomaterials for artificial photosynthesis require fast and robust unidirectional electron transfer (ET) from photosensitizers through charge-separation and accumulation units to redox-active catalytic sites. We explored the ultrafast time-scale limits of photo-induced charge transfer between a Ru(II)tris(bipyridine) derivative photosensitizer and PpcA, a 3-heme c-type cytochrome serving as a nanoscale biological wire. Four covalent attachment sites (K28C, K29C, K52C, and G53C) were engineered in PpcA enabling site-specific covalent labeling with expected donor-acceptor (DA) distances of 4–8 Å. X-ray scattering results demonstrated that mutations and chemical labeling did not disrupt the structure of the proteins. Time-resolved spectroscopy revealed three orders of magnitude difference in charge transfer rates for the systems with otherwise similar DA distances and the same number of covalent bonds separating donors and acceptors. All-atom molecular dynamics simulations provided additional insight into the structure-function requirements for ultrafast charge transfer and the requirement of van der Waals contact between aromatic atoms of photosensitizers and hemes in order to observe sub-nanosecond ET. This work demonstrates opportunities to utilize multi-heme c-cytochromes as frameworks for designing ultrafast light-driven ET into charge-accumulating biohybrid model systems, and ultimately for mimicking the photosynthetic paradigm of efficiently coupling ultrafast, light-driven electron transfer chemistry to multi-step catalysis within small, experimentally versatile photosynthetic biohybrid assemblies.

The rapid expansion of biomedical literature has provoked an increased development of advanced text mining tools to rapidly extract relevant events from the continuously increasing amount of knowledge published periodically in PubMed. However, bioinvestigators are still reluctant to use these tools for two reasons: i) a large volume of events is often extracted upon a query, and this volume is hard to manage, and ii) background events dominate search results and overshadow more pertinent published information, especially for domain experts. In this paper, we propose an approach that incorporates the temporal dimension of published events to the process of information extraction to improve data selection and prioritize more pertinent periodically published knowledge for scientists. Indeed, instead of providing the total knowledge associated with a PubMed query, which is usually a mix of trivial background information and nonbackground information, we propose a method that incorporates time and selects non background and highly relevant biological entities and events published over time for bioinvestigators. Before excluding background events from the total knowledge extracted, a quantification of their amount is also provided. This work is illustrated by a case study regarding Hepcidin gene publications over a decade, a duration that is sufficiently long enough to generate alternative views on the overall data extracted.

Cumulative experience with a variety of symbolic artifacts has been hypothesized as a source of young children's increasing sensitivity to new symbol-referent relations. Evidence for this hypothesis comes from transfer studies showing that experience with a relatively easy symbolic retrieval task improves performance on a more difficult task. Significant transfer was found for the 2-year-old children in the 3 studies reported here, even with relatively low levels of contextual support (according to the taxonomy of transfer by Barnett & Ceci, 2002). Transfer occurred even though the 2 tasks were encountered in very different settings and there was a prolonged (1-week) delay interval between them. Transfer also occurred to a much more difficult task (one that even 3-year-olds typically fail).

Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.

Abstract Despite the knowledge of complex prokaryotic‐transcription mechanisms, generalized rules, such as the simplified organization of genes into operons with well‐defined promoters and terminators, have had a significant role in systems analysis of regulatory logic in both bacteria and archaea. Here, we have investigated the prevalence of alternate regulatory mechanisms through genome‐wide characterization of transcript structures of ∼64% of all genes, including putative non‐coding RNAs in Halobacterium salinarum NRC‐1. Our integrative analysis of transcriptome dynamics and protein–DNA interaction data sets showed widespread environment‐dependent modulation of operon architectures, transcription initiation and termination inside coding sequences, and extensive overlap in 3′ ends of transcripts for many convergently transcribed genes. A significant fraction of these alternate transcriptional events correlate to binding locations of 11 transcription factors and regulators (TFs) inside operons and annotated genes—events usually considered spurious or non‐functional. Using experimental validation, we illustrate the prevalence of overlapping genomic signals in archaeal transcription, casting doubt on the general perception of rigid boundaries between coding sequences and regulatory elements.

Abstract In transcriptional regulatory networks, the coincident binding of a combination of factors to regulate a gene implies the existence of complex mechanisms to control both the gene expression profile and specificity of the response. Unraveling this complexity is a major challenge to biologists. Here, a novel network topology‐based clustering approach was applied to condition‐specific genome‐wide chromatin localization and expression data to characterize a dynamic transcriptional regulatory network responsive to the fatty acid oleate. A network of four (predicted) regulators of the response (Oaf1p, Pip2p, Adr1p and Oaf3p) was investigated. By analyzing trends in the network structure, we found that two groups of multi‐input motifs form in response to oleate, each controlling distinct functional classes of genes. This functionality is contributed in part by Oaf1p, which is a component of both types of multi‐input motifs and has two different regulatory activities depending on its binding context. The dynamic cooperation between Oaf1p and Pip2p appears to temporally synchronize the two different responses. Together, these data suggest a network mechanism involving dynamic combinatorial control for coordinating transcriptional responses.

Comentarios de José M. Margenat S.I., Hedwigh Marzloff y Juan A. Senent al discurso ante el Parlamento de la República Federal Alemana Sobre los fundamentos del Estado liberal de derecho de Benedicto XVI

Abstract Background High throughput sequencing has become an increasingly important tool for biological research. However, the existing software systems for managing and processing these data have not provided the flexible infrastructure that research requires. Results Existing software solutions provide static and well-established algorithms in a restrictive package. However as high throughput sequencing is a rapidly evolving field, such static approaches lack the ability to readily adopt the latest advances and techniques which are often required by researchers. We have used a loosely coupled, service-oriented infrastructure to develop SeqAdapt. This system streamlines data management and allows for rapid integration of novel algorithms. Our approach also allows computational biologists to focus on developing and applying new methods instead of writing boilerplate infrastructure code. Conclusion The system is based around the Addama service architecture and is available at our website as a demonstration web application, an installable single download and as a collection of individual customizable services.

Abstract Background Prostate cancer cells in primary tumors have been typed CD10-/CD13-/CD24hi/CD26+/CD38lo/CD44-/CD104-. This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure. Methods CD26+ cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells. Results The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines. Conclusions Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types.

Abstract Background As part of a National Institute of Allergy and Infectious Diseases funded collaborative project, we have performed over 150 microarray experiments measuring the response of C57/BL6 mouse bone marrow macrophages to toll-like receptor stimuli. These microarray expression profiles are available freely from our project web site http://www.innateImmunity-systemsbiology.org. Here, we report the development of a database of computationally predicted transcription factor binding sites and related genomic features for a set of over 2000 murine immune genes of interest. Our database, which includes microarray co-expression clusters and a host of web-based query, analysis and visualization facilities, is available freely via the internet. It provides a broad resource to the research community, and a stepping stone towards the delineation of the network of transcriptional regulatory interactions underlying the integrated response of macrophages to pathogens. Description We constructed a database indexed on genes and annotations of the immediate surrounding genomic regions. To facilitate both gene-specific and systems biology oriented research, our database provides the means to analyze individual genes or an entire genomic locus. Although our focus to-date has been on mammalian toll-like receptor signaling pathways, our database structure is not limited to this subject, and is intended to be broadly applicable to immunology. By focusing on selected immune-active genes, we were able to perform computationally intensive expression and sequence analyses that would currently be prohibitive if applied to the entire genome. Using six complementary computational algorithms and methodologies, we identified transcription factor binding sites based on the Position Weight Matrices available in TRANSFAC. For one example transcription factor (ATF3) for which experimental data is available, over 50% of our predicted binding sites coincide with genome-wide chromatin immnuopreciptation (ChIP-chip) results. Our database can be interrogated via a web interface. Genomic annotations and binding site predictions can be automatically viewed with a customized version of the Argo genome browser. Conclusion We present the Innate Immune Database (IIDB) as a community resource for immunologists interested in gene regulatory systems underlying innate responses to pathogens. The database website can be freely accessed at http://db.systemsbiology.net/IIDB.

Abstract Background The biological information in genomic expression data can be understood, and computationally extracted, in the context of systems of interacting molecules. The automation of this information extraction requires high throughput management and analysis of genomic expression data, and integration of these data with other data types. Results SBEAMS-Microarray, a module of the open-source Systems Biology Experiment Analysis Management System (SBEAMS), enables MIAME-compliant storage, management, analysis, and integration of high-throughput genomic expression data. It is interoperable with the Cytoscape network integration, visualization, analysis, and modeling software platform. Conclusion SBEAMS-Microarray provides end-to-end support for genomic expression analyses for network-based systems biology research.