Biomarkers in Sporadic and Familial Alzheimer's Disease.

J Alzheimers Dis. 2015;47(2):291-317

Authors: Lista S, O'Bryant SE, Blennow K, Dubois B, Hugon J, Zetterberg H, Hampel H

Abstract
Most forms of Alzheimer's disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the "exploratory biomarker discovery arena", proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.

PMID: 26401553 [PubMed - indexed for MEDLINE]

Silica distinctively affects cell wall features and lignocellulosic saccharification with large enhancement on biomass production in rice.

Plant Sci. 2015 Oct;239:84-91

Authors: Zhang J, Zou W, Li Y, Feng Y, Zhang H, Wu Z, Tu Y, Wang Y, Cai X, Peng L

Abstract
Rice is a typical silicon-accumulating crop with enormous biomass residues for biofuels. Silica is a cell wall component, but its effect on the plant cell wall and biomass production remains largely unknown. In this study, a systems biology approach was performed using 42 distinct rice cell wall mutants. We found that silica levels are significantly positively correlated with three major wall polymers, indicating that silica is associated with the cell wall network. Silicon-supplied hydroculture analysis demonstrated that silica distinctively affects cell wall composition and major wall polymer features, including cellulose crystallinity (CrI), arabinose substitution degree (reverse Xyl/Ara) of xylans, and sinapyl alcohol (S) proportion in three typical rice mutants. Notably, the silicon supplement exhibited dual effects on biomass enzymatic digestibility in the mutant and wild type (NPB) after pre-treatments with 1% NaOH and 1% H2SO4. In addition, silicon supply largely enhanced plant height, mechanical strength and straw biomass production, suggesting that silica rescues mutant growth defects. Hence, this study provides potential approaches for silicon applications in biomass process and bioenergy rice breeding.

PMID: 26398793 [PubMed - indexed for MEDLINE]

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

"Systems Biology"[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/07/12

PubMed comprises more than 24 million 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.

Selection on metabolic pathway function in the presence of mutation-selection-drift balance leads to rate-limiting steps that are not evolutionarily stable.

Biol Direct. 2016;11(1):31

Authors: Orlenko A, Teufel AI, Chi PB, Liberles DA

Abstract
BACKGROUND: While commonly assumed in the biochemistry community that the control of metabolic pathways is thought to be critical to cellular function, it is unclear if metabolic pathways generally have evolutionarily stable rate limiting (flux controlling) steps.
RESULTS: A set of evolutionary simulations using a kinetic model of a metabolic pathway was performed under different conditions to evaluate the evolutionary stability of rate limiting steps. Simulations used combinations of selection for steady state flux, selection against the cost of molecular biosynthesis, and selection against the accumulation of high concentrations of a deleterious intermediate. Two mutational regimes were used, one with mutations that on average were neutral to molecular phenotype and a second with a preponderance of activity-destroying mutations. The evolutionary stability of rate limiting steps was low in all simulations with non-neutral mutational processes. Clustering of parameter co-evolution showed divergent inter-molecular evolutionary patterns under different evolutionary regimes.
CONCLUSIONS: This study provides a null model for pathway evolution when compensatory processes dominate with potential applications to predicting pathway functional change. This result also suggests a possible mechanism in which studies in statistical genetics that aim to associate a genotype to a phenotype assuming independent action of variants may be mis-specified through a mis-characterization of the link between individual gene function and pathway function. A better understanding of the genotype-phenotype map has potential applications in differentiating between compensatory changes and directional selection on pathways as well as detecting SNPs and fixed differences that might have phenotypic effects.
REVIEWERS: This article was reviewed by Arne Elofsson, David Ardell, and Shamil Sunyaev.

PMID: 27393343 [PubMed - as supplied by publisher]

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

"Systems Biology"[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/07/09

PubMed comprises more than 24 million 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.

Mutation at a distance caused by homopolymeric guanine repeats in Saccharomyces cerevisiae.

Sci Adv. 2016 May;2(5):e1501033

Authors: McDonald MJ, Yu YH, Guo JF, Chong SY, Kao CF, Leu JY

Abstract
Mutation provides the raw material from which natural selection shapes adaptations. The rate at which new mutations arise is therefore a key factor that determines the tempo and mode of evolution. However, an accurate assessment of the mutation rate of a given organism is difficult because mutation rate varies on a fine scale within a genome. A central challenge of evolutionary genetics is to determine the underlying causes of this variation. In earlier work, we had shown that repeat sequences not only are prone to a high rate of expansion and contraction but also can cause an increase in mutation rate (on the order of kilobases) of the sequence surrounding the repeat. We perform experiments that show that simple guanine repeats 13 bp (base pairs) in length or longer (G 13+ ) increase the substitution rate 4- to 18-fold in the downstream DNA sequence, and this correlates with DNA replication timing (R = 0.89). We show that G 13+ mutagenicity results from the interplay of both error-prone translesion synthesis and homologous recombination repair pathways. The mutagenic repeats that we study have the potential to be exploited for the artificial elevation of mutation rate in systems biology and synthetic biology applications.

PMID: 27386516 [PubMed - as supplied by publisher]

New approaches and omics tools for mining of vaccine candidates against vector-borne diseases.

Mol Biosyst. 2016 Jul 7;

Authors: Kuleš J, Horvatić A, Guillemin N, Galan A, Mrljak V, Bhide M

Abstract
Vector-borne diseases (VBDs) present a major threat to human and animal health, as well as place a substantial burden on livestock production. As a way of sustainable VBD control, focus is set on vaccine development. Advances in genomics and other "omics" over the past two decades have given rise to a "third generation" of vaccines based on technologies such as reverse vaccinology, functional genomics, immunomics, structural vaccinology and the systems biology approach. The application of omics approaches is shortening the time required to develop the vaccines and increasing the probability of discovery of potential vaccine candidates. Herein, we review the development of new generation vaccines for VBDs, and discuss technological advancement and overall challenges in the vaccine development pipeline. Special emphasis is placed on the development of anti-tick vaccines that can quell both vectors and pathogens.

PMID: 27384976 [PubMed - as supplied by publisher]

Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants.

Eur J Heart Fail. 2016 Jul 7;

Authors: Linde C, Eriksson MJ, Hage C, Wallén H, Persson B, Corbascio M, Lundeberg J, Maret E, Ugander M, Persson H, Stockholm County/Karolinska Institutet 4D heart failure investigators

Abstract
AIMS: Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF ( https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf).
METHODS: Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis.
CONCLUSIONS: In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF.

PMID: 27384611 [PubMed - as supplied by publisher]

Neural oscillations as a signature of efficient coding in the presence of synaptic delays.

Elife. 2016 Jul 7;5

Authors: Chalk M, Gutkin B, Denève S

Abstract
Cortical networks exhibit 'global oscillations', where neural spikes are entrained to an underlying oscillatory rhythm, but where individual neurons fire irregularly. While the network dynamics underlying global oscillations are well characterised, their function is debated. Here, we show that such global oscillations are a direct consequence of optimal efficient coding in spiking networks with synaptic delays. To avoid firing unnecessary spikes, neurons must share information about the network state. Ideally, membrane potentials should be correlated and reflect a 'prediction error' while spikes themselves are uncorrelated and occur rarely. We show that the most efficient representation is achieved when: (i) spikes are entrained to a global Gamma rhythm (implying a consistent representation of the error); but (ii) few neurons fire on each cycle (implying high efficiency), while (iii) excitation and inhibition are tightly balanced. This suggests that cortical networks exhibiting such dynamics are tuned to achieve a maximally efficient population code.

PMID: 27383272 [PubMed - as supplied by publisher]

Molecular dynamics-based renement and validation with Resolution Exchange MDFF for sub-5 Å cryo-electron microscopy maps.

Elife. 2016 Jul 7;5

Authors: Singharoy A, Teo I, McGreevy R, Stone JE, Zhao J, Schulten K

Abstract
Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5-Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a convergence radius of ~25Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.2Å and 3.4Å resolution. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the respective macromolecules studied, captured employing local root mean square fluctuations. The MDFF tools are made available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services.

PMID: 27383269 [PubMed - as supplied by publisher]

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans.

Elife. 2016 Jul 6;5

Authors: Walhout AJ, Watson E, Olin-Sandoval V, Hoy MJ, Li CH, Louisse T, Yao V, Mori A, Holdorf AD, Troyanskaya OG, Ralser M

Abstract
Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.

PMID: 27383050 [PubMed - as supplied by publisher]

An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency.

Nucleic Acids Res. 2016 Feb 18;44(3):1203-15

Authors: Jo J, Hwang S, Kim HJ, Hong S, Lee JE, Lee SG, Baek A, Han H, Lee JI, Lee I, Lee DR

Abstract
Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such as Oct4, Sox2, Klf4 and Myc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.

PMID: 26740582 [PubMed - indexed for MEDLINE]

Predicting Dental Caries Outcomes in Children: A "Risky" Concept.

J Dent Res. 2016 Mar;95(3):248-54

Authors: Divaris K

Abstract
In recent years, unprecedented gains in the understanding of the biology and mechanisms underlying human health and disease have been made. In the domain of oral health, although much remains to be learned, the complex interactions between different systems in play have begun to unravel: host genome, oral microbiome with its transcriptome, proteome and metabolome, and more distal influences, including relevant behaviors and environmental exposures. A reasonable expectation is that this emerging body of knowledge can help improve the oral health and optimize care for individuals and populations. These goals are articulated by the National Institutes of Health as "precision medicine" and the elimination of health disparities. Key processes in these efforts are the discovery of causal factors or mechanistic pathways and the identification of individuals or population segments that are most likely to develop (any or severe forms of) oral disease. This article critically reviews the fundamental concepts of risk assessment and outcome prediction, as they relate to early childhood caries (ECC)-a common complex disease with significant negative impacts on children, their families, and the health system. The article highlights recent work and advances in methods available to estimate caries risk and derive person-level caries propensities. It further discusses the reasons for their limited utility in predicting individual ECC outcomes and informing clinical decision making. Critical issues identified include the misconception of defining dental caries as a tooth or surface-level condition versus a person-level disease; the fallacy of applying population-level parameters to individuals, termed privatization of risk; and the inadequacy of using frequentist versus Bayesian modeling approaches to derive individual disease propensity estimates. The article concludes with the notion that accurate caries risk assessment at the population level and "precision dentistry" at the person level are both desirable and achievable but must be based on high-quality longitudinal data and rigorous methodology.

PMID: 26647391 [PubMed - indexed for MEDLINE]

Systems-level organization of yeast methylotrophic lifestyle.

BMC Biol. 2015;13:80

Authors: Rußmayer H, Buchetics M, Gruber C, Valli M, Grillitsch K, Modarres G, Guerrasio R, Klavins K, Neubauer S, Drexler H, Steiger M, Troyer C, Al Chalabi A, Krebiehl G, Sonntag D, Zellnig G, Daum G, Graf AB, Altmann F, Koellensperger G, Hann S, Sauer M, Mattanovich D, Gasser B

Abstract
BACKGROUND: Some yeasts have evolved a methylotrophic lifestyle enabling them to utilize the single carbon compound methanol as a carbon and energy source. Among them, Pichia pastoris (syn. Komagataella sp.) is frequently used for the production of heterologous proteins and also serves as a model organism for organelle research. Our current knowledge of methylotrophic lifestyle mainly derives from sophisticated biochemical studies which identified many key methanol utilization enzymes such as alcohol oxidase and dihydroxyacetone synthase and their localization to the peroxisomes. C1 assimilation is supposed to involve the pentose phosphate pathway, but details of these reactions are not known to date.
RESULTS: In this work we analyzed the regulation patterns of 5,354 genes, 575 proteins, 141 metabolites, and fluxes through 39 reactions of P. pastoris comparing growth on glucose and on a methanol/glycerol mixed medium, respectively. Contrary to previous assumptions, we found that the entire methanol assimilation pathway is localized to peroxisomes rather than employing part of the cytosolic pentose phosphate pathway for xylulose-5-phosphate regeneration. For this purpose, P. pastoris (and presumably also other methylotrophic yeasts) have evolved a duplicated methanol inducible enzyme set targeted to peroxisomes. This compartmentalized cyclic C1 assimilation process termed xylose-monophosphate cycle resembles the principle of the Calvin cycle and uses sedoheptulose-1,7-bisphosphate as intermediate. The strong induction of alcohol oxidase, dihydroxyacetone synthase, formaldehyde and formate dehydrogenase, and catalase leads to high demand of their cofactors riboflavin, thiamine, nicotinamide, and heme, respectively, which is reflected in strong up-regulation of the respective synthesis pathways on methanol. Methanol-grown cells have a higher protein but lower free amino acid content, which can be attributed to the high drain towards methanol metabolic enzymes and their cofactors. In context with up-regulation of many amino acid biosynthesis genes or proteins, this visualizes an increased flux towards amino acid and protein synthesis which is reflected also in increased levels of transcripts and/or proteins related to ribosome biogenesis and translation.
CONCLUSIONS: Taken together, our work illustrates how concerted interpretation of multiple levels of systems biology data can contribute to elucidation of yet unknown cellular pathways and revolutionize our understanding of cellular biology.

PMID: 26400155 [PubMed - indexed for MEDLINE]

The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

Transplantation. 2016 Mar;100(3):497-505

Authors: Seifert ME, Hruska KA

Abstract
The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

PMID: 26356179 [PubMed - indexed for MEDLINE]

Analytical methods in sphingolipidomics: Quantitative and profiling approaches in food analysis.

J Chromatogr A. 2016 Jan 8;1428:16-38

Authors: Canela N, Herrero P, Mariné S, Nadal P, Ras MR, Rodríguez MÁ, Arola L

Abstract
In recent years, sphingolipidomics has emerged as an interesting omic science that encompasses the study of the full sphingolipidome characterization, content, structure and activity in cells, tissues or organisms. Like other omics, it has the potential to impact biomarker discovery, drug development and systems biology knowledge. Concretely, dietary food sphingolipids have gained considerable importance due to their extensively reported bioactivity. Because of the complexity of this lipid family and their diversity among foods, powerful analytical methodologies are needed for their study. The analytical tools developed in the past have been improved with the enormous advances made in recent years in mass spectrometry (MS) and chromatography, which allow the convenient and sensitive identification and quantitation of sphingolipid classes and form the basis of current sphingolipidomics methodologies. In addition, novel hyphenated nuclear magnetic resonance (NMR) strategies, new ionization strategies, and MS imaging are outlined as promising technologies to shape the future of sphingolipid analyses. This review traces the analytical methods of sphingolipidomics in food analysis concerning sample extraction, chromatographic separation, the identification and quantification of sphingolipids by MS and their structural elucidation by NMR.

PMID: 26275862 [PubMed - indexed for MEDLINE]

Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution.

PLoS Genet. 2016 Jul;12(7):e1006132

Authors: Mannakee BK, Gutenkunst RN

Abstract
The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein's rate of evolution. However, the relevance of these studies to evolutionary changes within proteins is unknown, because amino acid substitutions, unlike knockouts, often only slightly perturb protein activity. To quantify the phenotypic effect of small biochemical perturbations, we developed an approach to use computational systems biology models to measure the influence of individual reaction rate constants on network dynamics. We show that this dynamical influence is predictive of protein domain evolutionary rate within networks in vertebrates and yeast, even after controlling for expression level and breadth, network topology, and knockout effect. Thus, our results not only demonstrate the importance of protein domain function in determining evolutionary rate, but also the power of systems biology modeling to uncover unanticipated evolutionary forces.

PMID: 27380265 [PubMed - as supplied by publisher]

Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users.

PLoS One. 2016;11(7):e0158641

Authors: Piepenbrink MS, Samuel M, Zheng B, Carter B, Fucile C, Bunce C, Kiebala M, Khan AA, Thakar J, Maggirwar SB, Morse D, Rosenberg AF, Haughey NJ, Valenti W, Keefer MC, Kobie JJ

Abstract
BACKGROUND: Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles.
METHODS AND FINDINGS: A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy.
CONCLUSIONS: These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population.

PMID: 27379802 [PubMed - as supplied by publisher]

Editorial: Protein Interaction Networks in Health and Disease.

Front Genet. 2016;7:111

Authors: Petrakis S, Andrade-Navarro MA

PMID: 27379161 [PubMed - as supplied by publisher]

Silicon: Potential to Promote Direct and Indirect Effects on Plant Defense Against Arthropod Pests in Agriculture.

Front Plant Sci. 2016;7:744

Authors: Reynolds OL, Padula MP, Zeng R, Gurr GM

Abstract
Silicon has generally not been considered essential for plant growth, although it is well recognized that many plants, particularly Poaceae, have substantial plant tissue concentrations of this element. Recently, however, the International Plant Nutrition Institute [IPNI] (2015), Georgia, USA has listed it as a "beneficial substance". This reflects that numerous studies have now established that silicon may alleviate both biotic and abiotic stress. This paper explores the existing knowledge and recent advances in elucidating the role of silicon in plant defense against biotic stress, particularly against arthropod pests in agriculture and attraction of beneficial insects. Silicon confers resistance to herbivores via two described mechanisms: physical and biochemical/molecular. Until recently, studies have mainly centered on two trophic levels; the herbivore and plant. However, several studies now describe tri-trophic effects involving silicon that operate by attracting predators or parasitoids to plants under herbivore attack. Indeed, it has been demonstrated that silicon-treated, arthropod-attacked plants display increased attractiveness to natural enemies, an effect that was reflected in elevated biological control in the field. The reported relationships between soluble silicon and the jasmonic acid (JA) defense pathway, and JA and herbivore-induced plant volatiles (HIPVs) suggest that soluble silicon may enhance the production of HIPVs. Further, it is feasible that silicon uptake may affect protein expression (or modify proteins structurally) so that they can produce additional, or modify, the HIPV profile of plants. Ultimately, understanding silicon under plant ecological, physiological, biochemical, and molecular contexts will assist in fully elucidating the mechanisms behind silicon and plant response to biotic stress at both the bi- and tri-trophic levels.

PMID: 27379104 [PubMed - as supplied by publisher]