Deciphering the phylogenetic history of neuroserpin orthologs across metazoans by analysis of synteny and rare genomic characters

The superfamily of serine proteinase inhibitors (serpins) is involved in wide arrays of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression. The average protein size of a serpin family member is 350-400 amino acids, but gene structure varies in terms of number and position of exons and introns. All known serpins can be grouped into 16 clades and 10 orphan sequences. Vertebrate serpins can be conveniently classified into six sub-groups, based on three independent biological features - genomic organization, diagnostic amino acid sites and rare indels.
The objective of this study was to elucidate the phylogenetic kinships of serpins involved in surveying the secretory pathway routes against uncontrolled proteolytic activity. Though phylogenetic classification of vertebrate serpins into six groups based on gene organisation is well established, the evolutionary roots beyond the fish/tetrapod split are unresolved. This study illustrates that the analysis of microsynteny and other rare characters can provide insight into the intricate family history of metazoan serpins. Rare genomic characters/changes (RGC) are used to decipher that orthologs of neuroserpin, a prominent representative of vertebrate group 3 serpin genes, exist in early diverging deuterostomes and probably also in cnidarians, indicating that the origin of a mammalian serpin can be traced back far in the history of eumetazoans.
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Exploiting boundary states of imperfect spin chains for high-fidelity state transfer

We study transfer of a quantum state through XX spin chains with static imperfections. We combine the two standard approaches for state transfer based on (i) modulated couplings between neighboring spins throughout the spin chain and (ii) weak coupling of the outermost spins to an unmodulated spin chain. The combined approach allows us to design spin chains with modulated couplings and localized boundary states, permitting high-fidelity state transfer in the presence of random static imperfections of the couplings. The modulated couplings are explicitly obtained from an exact algorithm using the close relation between tridiagonal matrices and orthogonal polynomials [Linear Algebr. Appl. 21, 245 (1978)]. The implemented algorithm and a graphical user interface for constructing spin chains with boundary states (spinGUIn) are provided as Supplemental Material.Comment: 7 pages, 3 figures + spinGUIn description and Matlab files iepsolve.m, spinGUIn.fig, spinGUIn.

Signature Center for Computational Diagnostics Translating Experimental Technologies into Clinical Research

poster abstractThe goal of the Center for Computational Diagnostics [http://www.iupui.edu/~compdiag] is to serve as a “reactor” of innovative research for the integration of diverse high throughput technology into clinical trials to allow clinical researchers to obtain a more comprehensive view of the disease states. It has become clear that to better understand diseases we cannot continue to only focus on single genes, proteins or metabolites operating in single linear ordered pathways. Large scale high throughput technologies such as applied in genomics, proteomics and metabolomics allow for a more comprehensive view of the complex interactions occurring within body fluids or tissues at any one time. The Center operates by addressing the three different areas that are required to successfully integrate high throughput methodologies into translational research: 1) High throughput biospecimen banking; 2) Generation of high quality datasets and 3) Workflow development for data storage and analysis. To support high throughput bio-specimen banking we have co-developed caTissue Suite under the national caBIG effort. The key developments of the Center have been: 1. CaTrack, an intelligent barcode-based automatic data capture system 2. protocol-driven Study Calendar 3. xCaCORE, an innovative XML-based data import and export software program 4. Scalable, globally unique specimen identification utilizing an ISO Object Identifiers encoding scheme 5. Barcode generator and label printing We have implemented the Pediatric Biospecimen Repository to be able to develop and test these informatics tools. In addition to functioning as the development and test site for informatics research, the repository also develops research protocols and stores biospecimens for Pediatrics, Ophthalmology and Obstetrics. We also support protocol and data management related to biospecimens for the CTSI and the Fairbanks Institute. We currently have 92 active protocols and data on 119,319 specimens in our production instance of caTissue Suite. This includes specimens from 1200 well-defined healthy control subjects across all age groups including 600 children. To develop the computational and statistical workflows for data storage and analysis, we have generated large well-designed datasets for coronary artery disease (LC-MS/MS, NMR, protein antibody arrays); cancer (osteosarcoma and Wilms tumor; LC-MS/MS, NMR, protein antibody arrays) and ophthalmologic diseases (glaucoma; protein antibody arrays). Our main focus is to develop analytical workflows that translate the large datasets into relevant information for clinical researchers, focusing on the biological interpretation of the results. In this context we developed statistical models for protein quantification for LC-MS/MS and protein antibody arrays. These workflows were implemented in the open source statistical software R and published under the R-based project Bioconductor

Ancestry and evolution of a secretory pathway serpin

Kumar A, Ragg H. Ancestry and evolution of a secretory pathway serpin. BMC Evolutionary Biology. 2008;8(1): 250.Background:The serpin (serine protease inhibitor) superfamily constitutes a class of functionally highly diverse proteins usually encompassing several dozens of paralogs in mammals. Though phylogenetic classification of vertebrate serpins into six groups based on gene organisation is well established, the evolutionary roots beyond the fish/tetrapod split are unresolved. The aim of this study was to elucidate the phylogenetic relationships of serpins involved in surveying the secretory pathway routes against uncontrolled proteolytic activity. Results: Here, rare genomic characters are used to show that orthologs of neuroserpin, a prominent representative of vertebrate group 3 serpin genes, exist in early diverging deuterostomes and probably also in cnidarians, indicating that the origin of a mammalian serpin can be traced back far in the history of eumetazoans. A C-terminal address code assigning association with secretory pathway organelles is present in all neuroserpin orthologs, suggesting that supervision of cellular export/import routes by antiproteolytic serpins is an ancient trait, though subtle functional and compartmental specialisations have developed during their evolution. The results also suggest that massive changes in the exon-intron organisation of serpin genes have occurred along the lineage leading to vertebrate neuroserpin, in contrast with the immediately adjacent PDCD10 gene that is linked to its neighbour at least since divergence of echinoderms. The intron distribution pattern of closely adjacent and co-regulated genes thus may experience quite different fates during evolution of metazoans. Conclusion: This study demonstrates that the analysis of microsynteny and other rare characters can provide insight into the intricate family history of metazoan serpins. Serpins with the capacity to defend the main cellular export/import routes against uncontrolled endogenous and/or foreign proteolytic activity represent an ancient trait in eukaryotes that has been maintained continuously in metazoans though subtle changes affecting function and subcellular location have evolved. It is shown that the intron distribution pattern of neuroserpin gene orthologs has undergone substantial rearrangements during metazoan evolution

Effect of processing conditions on water mobility and cooking quality of gluten-free pasta. A magnetic resonance imaging study

A new approach for producing gluten-free pasta from hydrated (50\u202f\ub0C, 20\u202fmin) rice kernels, skipping the grinding step, was explored. Magnetic Resonance Imaging (MRI) was used to study the hydration kinetics of rice, by monitoring the time evolution of both proton density and water transverse-relaxation rate during water diffusion. Results showed that the optimal water diffusion was reached after 180\u202fmin, allowing the extrusion of hydrated rice kernels into pasta. MRI analysis also highlighted in cooked pasta gradients of water distribution and mobility, in agreement with the high shear force that was measured using the Kramer cell (1066.5 vs 896.4\u202fN). The high hydration in the external layers of pasta did not negatively affect the cooking quality (cooking loss, compression energy, firmness) of the product. MRI analysis provided experimental evidence for the optimization of early steps in the technological process of grains for the production of gluten-free pasta

The Effect of Molecular Weight on Passage of Proteins Through the Blood-Aqueous Barrier

Purpose: To determine the effect of molecular weight (MW) on the concentration of plasma-derived proteins in aqueous humor and to estimate the plasma-derived and eye-derived fractions for each protein. Methods: Aqueous humor and plasma samples were obtained during cataract surgery on an institutional review board–approved protocol. Protein concentrations were determined by ELISA and quantitative antibody microarrays. A total of 93 proteins were studied, with most proteins analyzed using 27 to 116 aqueous and 6 to 30 plasma samples. Results: Plasma proteins without evidence of intraocular expression by sequence tags were used to fit a logarithmic model relating aqueous-plasma ratio (AH:PL) to MW. The log(AH:PL) appears to be well predicted by the log(MW) (P 80), and 17 proteins had contribution from both plasma and eye tissue (IOF 20–80). Conclusions: Protein concentration of plasma-derived proteins in aqueous is nonlinearly dependent on MW in favor of smaller proteins. Our study demonstrates that for proper interpretation of results, proteomic studies evaluating changes in aqueous humor protein levels should take into account the plasma and eye-derived fractions

Locus of control in chronic fatigue syndrome : Does it matter?

The relationship between health locus of control and functioning in Chronic Fatigue Syndrome (CFS) was investigated. The hypothesis was that an internal health locus of control would be associated with less impairment in functioning than other dimensions of health locus of control. Prior research undertaken into CFS has been inconsistent in its finding's and it continues to be an area of controversial interpretations. A repeated measures design was used, 74 people participated at the initial stage of the study and 67 people participated in the second stage. The Functional Limitations Profile was used to assess levels of impairment. The Multidimensional Health Locus of Control was used to identify types of health locus of control orientation, and the Shapiro Control Inventory was used to establish a clearer picture of control issues. Correlations and t-tests were used to investigate the relationship between health locus of control and functioning. The results of these analyses indicated that an internal health locus of control was positively related to functioning. Multiple regression analysis was performed and showed that an internal health locus of control could successfully predict functioning measured at the second stage of the study. An unexpected discovery was that a doctor's health locus of control impacted negatively on functioning. The Shapiro Control Inventory revealed that the CFS sample fell within the normal range in the majority of control areas, but was outside the normal range in only six of the 23 control areas. These findings indicated that health locus of control does play an important role in CFS. It was therefore concluded that increasing a patient's sense of control and reflecting this in the treatment regime of CFS would aid recovery

Migration of Langerhans Cells from Carcinogen-Treated Sheep Skin

To define the mechanism(s) of carcinogen depletion of Langerhans cells (LC) from skin, the migration of LC from the skin to the regional lymph node was examined in carcinogen-treated, antigen-treated, and control sheep. This was assessed by cannulation of afferent lymphatic vessels that drain the treated areas of skin or the efferent lymphatic draining the regional lymph node. Cells draining from test or control skin were continuously collected and enumerated by indirect immunofluorescence and flow cytometry using specific anti-CD1 monoclonal antibodies. There was a marked increase in the rate of LC migration in the 8h following the application of the contact sensitizing antigen trinitrochlorobenzene (TNCB). The chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) triggered a tenfold-greater migration of LC compared with TNCB—with the peak response at 5 d. After DMBA treatment LC were also detected in the efferent lymph of the regional lymph node. It is concluded that the depletion of LC from carcinogentreated skin is due to the increased LC migration and not carcinogen-induced cell death