Rampant exchange of the structure and function of extramembrane domains between membrane and water soluble proteins.

Of the membrane proteins of known structure, we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure. Moreover, 41% of known water soluble protein structures share a domain with an already known membrane protein structure. We also found that functional residues are frequently conserved between extramembrane domains of membrane and soluble proteins that share structural similarity. These results suggest membrane and soluble proteins readily exchange domains and their attendant functionalities. The exchanges between membrane and soluble proteins are particularly frequent in eukaryotes, indicating that this is an important mechanism for increasing functional complexity. The high level of structural overlap between the two classes of proteins provides an opportunity to employ the extensive information on soluble proteins to illuminate membrane protein structure and function, for which much less is known. To this end, we employed structure guided sequence alignment to elucidate the functions of membrane proteins in the human genome. Our results bridge the gap of fold space between membrane and water soluble proteins and provide a resource for the prediction of membrane protein function. A database of predicted structural and functional relationships for proteins in the human genome is provided at sbi.postech.ac.kr/emdmp

Domain-mediated interactions for protein subfamily identification

Within a protein family, proteins with the same domain often exhibit different cellular functions, despite the shared evolutionary history and molecular function of the domain. We hypothesized that domain-mediated interactions (DMIs) may categorize a protein family into subfamilies because the diversified functions of a single domain often depend on interacting partners of domains. Here we systematically identified DMI subfamilies, in which proteins share domains with DMI partners, as well as with various functional and physical interaction networks in individual species. In humans, DMI subfamily members are associated with similar diseases, including cancers, and are frequently co-associated with the same diseases. DMI information relates to the functional and evolutionary subdivisions of human kinases. In yeast, DMI subfamilies contain proteins with similar phenotypic outcomes from specific chemical treatments. Therefore, the systematic investigation here provides insights into the diverse functions of subfamilies derived from a protein family with a link-centric approach and suggests a useful resource for annotating the functions and phenotypic outcomes of proteins.11Ysciescopu

Network rewiring is an important mechanism of gene essentiality change.

Gene essentiality changes are crucial for organismal evolution. However, it is unclear how essentiality of orthologs varies across species. We investigated the underlying mechanism of gene essentiality changes between yeast and mouse based on the framework of network evolution and comparative genomic analysis. We found that yeast nonessential genes become essential in mouse when their network connections rapidly increase through engagement in protein complexes. The increased interactions allowed the previously nonessential genes to become members of vital pathways. By accounting for changes in gene essentiality, we firmly reestablished the centrality-lethality rule, which proposed the relationship of essential genes and network hubs. Furthermore, we discovered that the number of connections associated with essential and non-essential genes depends on whether they were essential in ancestral species. Our study describes for the first time how network evolution occurs to change gene essentiality

Finding causal paths between safety management system factors and accident precursors

Understanding the causal relationships between safety management system (SMS) factors and accident precursors helps construction organizations identify which factors require improvement upon observing an accident precursor. Previous research has not clearly distinguished between SMS factors and accident precursors. This background examines the relationships between SMS factors and accident precursors using empirical data. Specifically, five structural equation models (SEMs) were developed to map causal paths between SMS factors and accident precursors. Each of the SEMs helps identify what specific SMS factors would have a significant influence on the occurrence of a particular type of accident precursor. These models can thus help describe what specific SMS factors would need to be improved when a certain type of accident precursor appears on site. The SEM results show in particular that the occurrence of accident precursors can be attributed largely to adverse project conditions such as project schedule pressure, reworks, and change orders. Construction organizations may capitalize on these findings by prioritizing safety management resources to address specific observed accident precursors in a more informed and targeted manner

Evolutionary coupling analysis identifies the impact of disease-associated variants at less-conserved sites

Genome-wide association studies have discovered a large number of genetic variants in human patients with the disease. Thus, predicting the impact of these variants is important for sorting disease-associated variants (DVs) from neutral variants. Current methods to predict the mutational impacts depend on evolutionary conservation at the mutation site, which is determined using homologous sequences and based on the assumption that variants at well-conserved sites have high impacts. However, many DVs at less-conserved but functionally important sites cannot be predicted by the current methods. Here, we present a method to find DVs at less-conserved sites by predicting the mutational impacts using evolutionary coupling analysis. Functionally important and evolutionarily coupled sites often have compensatory variants on cooperative sites to avoid loss of function. We found that our method identified known intolerant variants in a diverse group of proteins. Furthermore, at less-conserved sites, we identified DVs that were not identified using conservation-based methods. These newly identified DVs were frequently found at protein interaction interfaces, where species-specific mutations often alter interaction specificity. This work presents a means to identify less-conserved DVs and provides insight into the relationship between evolutionarily coupled sites and human DVs.11Ysciescopu

OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research

Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.1127Ysciescopu

Selective laser ablation of metal thin films using ultrashort pulses

Selective thin-film removal is needed in many microfabrication processes such as 3-D patterning of optoelectronic devices and localized repairing of integrated circuits. Various wet or dry etching methods are available, but laser machining is a tool of green manufacturing as it can remove thin films by ablation without use of toxic chemicals. However, laser ablation causes thermal damage on neighboring patterns and underneath substrates, hindering its extensive use with high precision and integrity. Here, using ultrashort laser pulses of sub-picosecond duration, we demonstrate an ultrafast mechanism of laser ablation that leads to selective removal of a thin metal film with minimal damage on the substrate. The ultrafast laser ablation is accomplished with the insertion of a transition metal interlayer that offers high electron-phonon coupling to trigger vaporization in a picosecond timescale. This contained form of heat transfer permits lifting off the metal thin-film layer while blocking heat conduction to the substrate. Our ultrafast scheme of selective thin film removal is analytically validated using a two-temperature model of heat transfer between electrons and phonons in material. Further, experimental verification is made using 0.2 ps laser pulses by micropatterning metal films for various applications.Comment: 19 pages, 4 figures. This manuscript has been submitted to International Journal of Precision Engineering and Manufacturing-Green Technolog

OASIS: Online Application for the Survival Analysis of Lifespan Assays Performed in Aging Research

Aging is a fundamental biological process. Characterization of genetic and environmental factors that influence lifespan is a crucial step toward understanding the mechanisms of aging at the organism level. To capture the different effects of genetic and environmental factors on lifespan, appropriate statistical analyses are needed.We developed an online application for survival analysis (OASIS) that helps conduct various novel statistical tasks involved in analyzing survival data in a user-friendly manner. OASIS provides standard survival analysis results including Kaplan-Meier estimates and mean/median survival time by taking censored survival data. OASIS also provides various statistical tests including comparison of mean survival time, overall survival curve, and survival rate at specific time point. To visualize survival data, OASIS generates survival and log cumulative hazard plots that enable researchers to easily interpret their experimental results. Furthermore, we provide statistical methods that can analyze variances among survival datasets. In addition, users can analyze proportional effects of risk factors on survival.OASIS provides a platform that is essential to facilitate efficient statistical analyses of survival data in the field of aging research. Web application and a detailed description of algorithms are accessible from http://sbi.postech.ac.kr/oasis

Phylogenetic analysis of ABCG subfamily proteins in plants: functional clustering and coevolution with ABCGs of pathogens

ABCG subfamily proteins are highly enriched in terrestrial plants. Many of these proteins secrete secondary metabolites that repel or inhibit pathogens. To establish why the ABCG subfamily proteins proliferated extensively during evolution, we constructed phylogenetic trees from a broad range of eukaryotic organisms. ABCG proteins were massively duplicated in land plants and in oomycetes, a group of agronomically important plant pathogens, which prompted us to hypothesize that plant and pathogen ABCGs coevolved. Supporting this hypothesis, full‐size ABCGs in host plants (Arabidopsis thaliana and Glycine max) and their pathogens (Hyaloperonospora arabidopsidis and Phytophthora sojae, respectively) had similar divergence times and patterns. Furthermore, generalist pathogens with broad ranges of host plants have diversified more ABCGs than their specialist counterparts. The hypothesis was further tested using an example pair of ABCGs that first diverged during multiplication in a host plant and its pathogen: AtABCG31 of A. thaliana and HpaP802307 of H. arabidopsidis. AtABCG31 expression was activated following infection with H. arabidopsidis, and disrupting AtABCG31 led to increased susceptibility to H. arabidopsidis. Together, our results suggest that ABCG genes in plants and their oomycete pathogens coevolved in an arms race, to extrude secondary metabolites involved in the plant's defense response against pathogens.11Ysciescopu

Functional characteristics of calcitonin gene-related peptide receptors in human Ewing's sarcoma WE-68 cells

AbstractCalcitonin gene-related peptide (CGRP) receptor activity was studied in WE-68 human Ewing's sarcoma cells. 125I-human CGRP bound in a time-dependent, reversible and saturable manner. Scatchard plots were compatible with the presence of a homogenous population of CGRP receptors with high affinity (Kd = 15 pM, and Bmax = 1.9 fmolmg protein). The potency order of unlabeled peptides, in the presence of radioligand, was: human CGRP-II > human CGRP = chick CGRP > rat CGRP = rat [Tyro]CGRP > human [Tyro] CGRP > > salmon calcitonin (CT) > rat [Tyro]CGRP-(28-37). Each peptide except CT and [Tyio]CGRP-(28-37) stimulated cyclic AMP generation in a concentration-dependent manner, and the relative potencies paralleled their relative ability in inhibiting 125I-human CGRP binding. We conclude that WE-68 Ewing's sarcoma cells express genuine CGRP receptors which upon activation lead to stimulation of cyclic AMP formation.Calcitonin gene-related peptide; Calcitonin; cyclic AMP; (Human; Ewing's sarcoma cell