Localizome: a server for identifying transmembrane topologies and TM helices of eukaryotic proteins utilizing domain information

The Localizome server predicts the transmembrane (TM) helix number and TM topology of a user-supplied eukaryotic protein and presents the result as an intuitive graphic representation. It utilizes hmmpfam to detect the presence of Pfam domains and a prediction algorithm, Phobius, to predict the TM helices. The results are combined and checked against the TM topology rules stored in a protein domain database called LocaloDom. LocaloDom is a curated database that contains TM topologies and TM helix numbers of known protein domains. It was constructed from Pfam domains combined with Swiss-Prot annotations and Phobius predictions. The Localizome server corrects the combined results of the user sequence to conform to the rules stored in LocaloDom. Compared with other programs, this server showed the highest accuracy for TM topology prediction: for soluble proteins, the accuracy and coverage were 99 and 75%, respectively, while for TM protein domain regions, they were 96 and 68%, respectively. With a graphical representation of TM topology and TM helix positions with the domain units, the Localizome server is a highly accurate and comprehensive information source for subcellular localization for soluble proteins as well as membrane proteins. The Localizome server can be found at

Sorbus alnifolia protects dopaminergic neurodegeneration in Caenorhabditis elegans

Context: The twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neuro- logical disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson’s disease (PD). Objective: This study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans. Materials and methods: To test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMPþ) in PC12 cells and C. elegans (400 lM and 2 mM of MMPþ, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA’s effects on DA neurode- generation in C. elegans. Aggregation of a-synuclein was observed using NL5901 strain (unc-54p::a- synuclein::YFP). MESA’s protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity. Results: MESA restored MPPþ-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter a-synuclein aggregation. Discussion and conclusions: These results revealed that MESA protects DA neurodegeneration and recov- ers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD

A protein domain interaction interface database: InterPare.

BACKGROUND: Most proteins function by interacting with other molecules. Their interaction interfaces are highly conserved throughout evolution to avoid undesirable interactions that lead to fatal disorders in cells. Rational drug discovery includes computational methods to identify the interaction sites of lead compounds to the target molecules. Identifying and classifying protein interaction interfaces on a large scale can help researchers discover drug targets more efficiently. DESCRIPTION: We introduce a large-scale protein domain interaction interface database called InterPare http://interpare.net. It contains both inter-chain (between chains) interfaces and intra-chain (within chain) interfaces. InterPare uses three methods to detect interfaces: 1) the geometric distance method for checking the distance between atoms that belong to different domains, 2) Accessible Surface Area (ASA), a method for detecting the buried region of a protein that is detached from a solvent when forming multimers or complexes, and 3) the Voronoi diagram, a computational geometry method that uses a mathematical definition of interface regions. InterPare includes visualization tools to display protein interior, surface, and interaction interfaces. It also provides statistics such as the amino acid propensities of queried protein according to its interior, surface, and interface region. The atom coordinates that belong to interface, surface, and interior regions can be downloaded from the website. CONCLUSION: InterPare is an open and public database server for protein interaction interface information. It contains the large-scale interface data for proteins whose 3D-structures are known. As of November 2004, there were 10,583 (Geometric distance), 10,431 (ASA), and 11,010 (Voronoi diagram) entries in the Protein Data Bank (PDB) containing interfaces, according to the above three methods. In the case of the geometric distance method, there are 31,620 inter-chain domain-domain interaction interfaces and 12,758 intra-chain domain-domain interfaces

Oxygen-Releasing Composites: A Promising Approach in the Management of Diabetic Foot Ulcers

In diabetes, lower extremity amputation (LEA) is an irreversible diabetic-related complication that easily occurs in patients with diabetic foot ulcers (DFUs). Because DFUs are a clinical outcome of different causes including peripheral hypoxia and diabetic foot infection (DFI), conventional wound dressing materials are often insufficient for supporting the normal wound healing potential in the ulcers. Advanced wound dressing development has recently focused on natural or biocompatible scaffolds or incorporating bioactive molecules. This review directs attention to the potential of oxygenation of diabetic wounds and highlights current fabrication techniques for oxygen-releasing composites and their medical applications. Based on different oxygen-releasable compounds such as liquid peroxides and solid peroxides, for example, a variety of oxygen-releasing composites have been fabricated and evaluated for medical applications. This review provides the challenges and limitations of utilizing current oxygen releasable compounds and provides perspectives on advancing oxygen releasing composites for diabetic-related wounds associated with DFUs

Antihypertensive and Renal Protective Effects of Oryeongsan in Spontaneously Hypertensive Rats

Oryeongsan (ORS), a traditional medicine used to regulate body fluids, has a long history of use as a diuretic in Korea, China, and Japan. ORS is commonly thought to lower blood pressure, but high-quality data on its effects are sparse. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP). Then, 10 mL/kg of vehicle (distilled water) or 200 mg/kg of ORS extract were administered orally once a day for 3 weeks. SBP and DBP were measured at weeks 1, 2, and 3. At the end of the experiment, blood was collected, and kidneys were removed for histology. By the 2nd and 3rd week after initiation of treatment, the ORS-treated group had significantly lower SBP than control-treated rats (191.3 ± 6.5 vs. 206.3 ± 9.8 mmHg, p = 0.022 at the 2nd week; 195.8 ± 7.8 vs. 217.0 ± 8.1 mmHg, p = 0.003 at the 3rd week, respectively). The ORS-treated group trended toward having a lower DBP than control, but there was no significant difference. Blood urea nitrogen (BUN) and serum creatinine (Cr) were not different between the ORS-treated and control groups (BUN: 23.7 ± 1.1 vs. 22.7 ± 2.8 mg/dL, p = 0.508; Cr: 19.0 ± 2.2 vs. 21.6 ± 2.1 μM, p = 0.083, respectively). The percentage of renal tissue affected by tubulointerstitial fibrosis was significantly lower in the ORS-treated group (1.68 ± 0.60) compared to controls (3.17 ± 0.96, p = 0.019). These findings suggest that treatment with ORS reduces SBP and ameliorates renal damage in SHR

In Vivo Animal Study of a Highly Viscous N-butyl Cyanoacrylate Medical Adhesive for Intravenous Embolization

N-butyl cyanoacrylate (NBCA) is a liquid monomer that undergoes an exothermic polymerization reaction to form a solid upon initiation with hydroxyl anions. Recently, EGpresto, a highly viscous NBCA-based adhesive, has been developed for vascular-occlusion purposes. In this study, we investigated the heat of polymerization of EGpresto and compared the results with those of a low-viscosity NBCA glue. Results show that EGpresto exhibited a lower heat of polymerization (64 ± 7 °C vs. 34 ± 1 °C). This was due to its high viscosity, which resulted in a delayed polymerization time. To investigate the efficacy and safety of EGpresto for intravenous embolization, a 14 d in vivo animal test was conducted using three pigs. Five cc of EGpresto was injected into the epigastric vein of each animal. Complete postoperative vein occlusion was confirmed at 7 and 14 d by ultrasonographic visualization. After the animals were sacrificed, the operated and unoperated veins were exposed, and the injected adhesive was found without migration. During the histology, the injected adhesive was not found in the inner or outer vein walls, and the immune reactions seemed to be the only foreign-body reaction, showing that EGpresto is a non-toxic and safe intravascular embolic agent

The Atom of Evolution

The main mechanism of evolution is that biological entities change, are selected, and reproduce. We propose a different concept in terms of the main agent or atom of evolution: in the biological world, not an individual object, but its interactive network is the fundamental unit of evolution. The interaction network is composed of interaction pairs of information objects that have order information. This indicates a paradigm shift from 3D biological objects to an abstract network of information entities as the primary agent of evolution. It forces us to change our views about how organisms evolve and therefore the methods we use to analyze evolution.clos

Sorbus alnifolia protects dopaminergic neurodegeneration in Caenorhabditis elegans

Context: The twigs of Sorbus alnifolia (Sieb. et Zucc.) K. Koch (Rosaceae) have been used to treat neuro- logical disorders as a traditional medicine in Korea. However, there are limited data describing the efficacy of S. alnifolia in Parkinson"s disease (PD).Objective: This study was conducted to identify the protective effects of the methanol extracts of S. alnifolia (MESA) on the dopaminergic (DA) neurodegeneration in Caenorhabditis elegans.Materials and methods: To test the neuroprotective action of MESA, viability assay was performed after 48 h exposure to 1-methyl-4-phenylpyridine (MMPþ) in PC12 cells and C. elegans (400 lM and 2 mM of MMPþ, respectively). Fluorescence intensity was quantified using transgenic mutants such as BZ555 (Pdat-1::GFP) and and UA57 (Pdat-1::GFP and Pdat-1::CAT-2) to determine MESA"s effects on DA neurode- generation in C. elegans. Aggregation of a-synuclein was observed using NL5901 strain (unc-54p::a- synuclein::YFP). MESA"s protective effects on the DA neuronal functions were examined by food-sensing assay. Lifespan assay was conducted to test the effects of MESA on the longevity.Results: MESA restored MPPþ-induced loss of viability in both PC12 cells and C. elegans (85.8% and 54.9%, respectively). In C. elegans, MESA provided protection against chemically and genetically-induced DA neurodegeneration, respectively. Moreover, food-sensing functions were increased 58.4% by MESA in the DA neuron degraded worms. MESA also prolonged the average lifespan by 25.6%. However, MESA failed to alter a-synuclein aggregation.Discussion and conclusions: These results revealed that MESA protects DA neurodegeneration and recov- ers diminished DA neuronal functions, thereby can be a valuable candidate for the treatment of PD