Protein phosphatase 2a (PP2A) binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3

Background

The repertoire of the antigen-binding receptors originates from the rearrangement of immunoglobulin and T-cell receptor genetic loci in a process known as V(D)J recombination. The initial site-specific DNA cleavage steps of this process are catalyzed by the lymphoid specific proteins RAG1 and RAG2. The majority of studies on RAG1 and RAG2 have focused on the minimal, core regions required for catalytic activity. Though not absolutely required, non-core regions of RAG1 and RAG2 have been shown to influence the efficiency and fidelity of the recombination reaction.

Results

Using a partial proteolysis approach in combination with bioinformatics analyses, we identified the domain boundaries of a structural domain that is present in the 380-residue N-terminal non-core region of RAG1. We term this domain the Central Non-core Domain (CND; residues 87-217).

Conclusions

We show how the CND alone, and in combination with other regions of non-core RAG1, functions in nuclear localization, zinc coordination, and interactions with nucleic acid. Together, these results demonstrate the multiple roles that the non-core region can play in the function of the full length protein.     

Microfluidic approaches for gene delivery and gene therapy

Recent advances in microfluidics have created new and exciting prospects for gene delivery and therapy. The micro-scaled environment within microfluidic systems enables precise control and optimization of multiple processes and techniques used in gene transfection and the production of gene and drug transporters. Traditional non-viral gene transfection methods, such as electroporation, microinjection and optical gene transfection, are improved from the use of innovative microfluidic systems. Additionally, microfluidic systems have also made the production of many viral and non-viral vectors controlled, automated, and reproducible. In summary, the development and application of microfluidic systems are producing increased efficiency in gene delivery and promise improved gene therapy results.     

Versatile grafting approaches to star-shaped POSS-containing hybrid polymers using RAFT polymerization and click chemistry

An alkyne-bearing polyhedral oligomeric silsesquioxane (POSS) core was used to prepare POSS-containing polymer hybrids using 'grafting to' or 'grafting from' strategies in combination with reversible chain transfer and click chemistry.     

Anti-inflammatory and antioxidant components from Hygroryza aristata

Twenty-six known compounds and two new compounds, including a new lignan, (7S*,8R*,7'R*,8'S*)-icariol A?-9-O-β-xylopyranoside (1), and a new indole alkaloid, hygarine (2), were isolated from the extracts of Hygroryza aristata (Gramineae). The structures of all compounds were elucidated on the basis of NMR spectral analysis. The compounds (-)-epigallocatechin-3-O-gallate (4) and (-)-epicatechin-3-O-gallate (5) possess free radical scavenging activities and compound 1 could inhibit superoxide anion generation and elastase release by fMLP/CB-induced human neutrophils with IC?? values of 19.33 ± 0.86 and 24.14 ± 1.59 μM, respectively.     

Restoration of electric footshock-induced immunosuppression in mice by Gynostemma pentaphyllum components

The immunomodulatory effects of the ethanol extract of Gynostemma pentaphyllum (GP-EX) were examined in electric footshock (EFS)-stressed mice. The mice were orally administered various doses of GP-EX for 7 days before exposure to EFS (duration: 3 min, interval: 10 s, intensity: 2 mA) once a day from day 8 for 14 days with continuous daily feeding of GP-EX. Oral administration of GP-EX to mice prevented EFS stress-induced immunosuppression as determined by the lymphoid organ (thymus and spleen) weight and cellularity. In addition, oral administration of GP-EX restored EFS-suppressed functional properties of mature lymphocytes in terms of concanavalin A-induced proliferation of splenocytes and lipopolysaccharide-induced cytokine production (TNF-α, IL-1β). Furthermore, we found that mice that were orally administered with GP-EX generated much more potent ovalbumin-specific cytotoxic T lymphocyte responses upon intravenous ovalbumin injection compared to the untreated controls. These results demonstrate that oral administration of the ethanol extract of Gynostemma pentaphyllum could increase host defense in immunocompromised situations such as stress-induced immunosuppression.     

Echinoclerodane A: A New Bioactive Clerodane-Type Diterpenoid from a Gorgonian Coral <em>Echinomuricea</em> sp

A new clerodane-type diterpenoid, echinoclerodane A (1), was isolated from a Formosan gorgonian coral Echinomuricea sp. The structure of 1 was elucidated by spectroscopic methods. Echinoclerodane A (1) is the first clerodane-type compound obtained from the marine organisms belonging to the phylum Cnidaria. Echinoclerodane A (1) exhibited moderate cytotoxicity toward MOLT-4, HL-60, DLD-1 and LoVo tumor cells and inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.     

Effect of electrospun non-woven mats of dibutyryl chitin/poly(lactic acid) blends on wound healing in hairless mice

The aim of this study was to examine the proliferative ability of dibutyryl chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using the advantages of DBCNFM, such as high porosity and high surface area to volume. The cell spreading activity of DBC was verified through a cell spreading assay in scratched human HaCaT keratinocytes. Scratch wound experiments showed that DBC notably accelerates the spreading rate of HaCaT keratinocytes in a dose dependent manner. The molecular aspects of the healing process were also investigated by hematoxylin & eosin staining of the healed skin, displaying the degrees of reepithelialization and immunostaining on extracellular matrix synthesis and remodeling of the skin. Topical application of DBCNFM significantly reduced skin wound rank scores and increased the skin remodeling of the wounded hairless mice in a dose dependent way. Furthermore, DBCNFM notably increased the expression of the type 1 collagen and filaggrin. These results demonstrate that DBC efficiently accelerates the proliferation of HaCaT keratinocytes and DBCNFM notably increases extracellular matrix synthesis on remodeling of the skin, and these materials are a good candidate for further evaluation as an effective wound healing agent.     

A non-volatile memory device consisting of graphene oxide covalently functionalized with ionic liquid

We introduce non-volatile resistive crossbar memory based on ionic liquid covalently functionalized on a partially reduced graphene oxide (PrGO). The write-read-erase-read (WRER) cycles were very stable after several hundred cycles and the retention time of both the ON and OFF states was stable for over 1000 s, indicating that the device we developed can function as a non-volatile memory device.     

Pressure and temperature dependence of the decomposition pathway of LiBH4

The decomposition pathway is crucial for the applicability of LiBH(4) as a hydrogen storage material. We discuss and compare the different decomposition pathways of LiBH(4) according to the thermodynamic parameters and show the experimental ways to realize them. Two pathways, i.e. the direct decomposition into boron and the decomposition via Li(2)B(12)H(12), were realized under appropriate conditions, respectively. By applying a H(2) pressure of 50 bar at 873 K or 10 bar at 700 K, LiBH(4) is forced to decompose into Li(2)B(12)H(12). In a lower pressure range of 0.1 to 10 bar at 873 K and 800 K, the concurrence of both decomposition pathways is observed. Raman spectroscopy and (11)B MAS NMR measurements confirm the formation of an intermediate Li(2)B(12)H(12) phase (mostly Li(2)B(12)H(12) adducts, such as dimers or trimers) and amorphous boron.