The Possible Structural Models for Polyglutamine Aggregation: A Molecular Dynamics Simulations Study

Abstract

Huntington's disease is a neurodegenerative disorder caused by a polyglutamine (polyQ) expansion near the N-terminus of huntingtin. Previous studies have suggested that polyQ aggregation occurs only when the number of glutamine (Q) residues is more than 36-40, the disease threshold. However, the structural characteristics of polyQ nucleation in the very early stage of aggregation still remain elusive. In this study, we designed 18 simulation trials to determine the possible structural models for polyQ nucleation and aggregation with various shapes and sizes of initial β-helical structures, such as left-handed circular, right-handed rectangular, and left- and right-handed triangular. Our results show that the stability of these models significantly increases with increasing the number of rungs, while it is rather insensitive to the number of Qs in each rung. In particular, the 3-rung β-helical models are stable when they adopt the left-handed triangular and right-handed rectangular conformations due to the fact that they preserve high β-turn and β-sheet contents, respectively, during the simulation courses. Thus, we suggested that these two stable β-helical structures with at least 3 rungs might serve as the possible nucleation seeds for polyQ depending on how the structural elements of β-turn and β-sheet are sampled and preserved during the very early stage of aggregation.     

The Vaccinium corymbosum FLOWERING LOCUS T-like gene (VcFT): a flowering activator reverses photoperiodic and chilling requirements in blueberry

Key message

The blueberry FLOWERING LOCUS T ( FT )-like gene ( VcFT ) cloned from the cDNA of a tetraploid, northern highbush blueberry ( Vaccinium corymbosum L.) is able to reverse the photoperiodic and chilling requirements and drive early and continuous flowering.

Abstract

Blueberry is a woody perennial bush with a longer juvenile period than annual crops, requiring vernalization to flower normally. Few studies have been reported on the molecular mechanism of flowering in blueberry or other woody plants. Because FLOWERING LOCUS T (FT) from Arabidopsis thaliana plays a multifaceted role in generating mobile molecular signals to regulate plant flowering time, isolation and functional analysis of the blueberry (Vaccinium corymbosum L.) FT-like gene (VcFT) will facilitate the elucidation of molecular mechanisms of flowering in woody plants. Based on EST sequences, a 525-bpVcFT was identified and cloned from the cDNA of a tetraploid, northern highbush blueberry cultivar, Bluecrop. Ectopic expression of 35S:VcFT in tobacco induced flowering an average of 28 days earlier than wild-type plants. Expression of the 35S:VcFT in the blueberry cultivar Aurora resulted in an extremely early flowering phenotype, which flowered not only during in vitro culture, a growth stage when nontransgenic shoots had not yet flowered, but also in 6–10-week old, soil-grown transgenic plants, in contrast to the fact that at least 1 year and 800 chilling hours are required for the appearance of the first flower of both nontransgenic ‘Aurora’ and transgenic controls with the gusA. These results demonstrate that the VcFT is a functional floral activator and overexpression of the VcFT is able to reverse the photoperiodic and chilling requirements and drive early and continuous flowering.     

Multiphoton tomography visualizes collagen fibers in the tumor microenvironment that maintain cancer‐cell anchorage and shape

Second harmonic generation (SHG) multiphoton imaging can visualize fibrillar collagen in tissues. SHG has previously shown that fibrillar collagen is altered in various types of cancer. In the present study, in vivo high resolution SHG multi‐photon tomography in living mice was used to study the relationship between cancer cells and intratumor collagen fibrils. Using green fluorescent protein (GFP) to visualize cancer cells and SHG to image collagen, we demonstrated that collagen fibrils provide a scaffold for cancer cells to align themselves and acquire optimal shape. These results suggest a new paradigm for a stromal element of tumors: their role in maintaining anchorage and shape of cancer cells that may enable them to proliferate. J. Cell. Biochem. 114: 99–102, 2012. © 2012 Wiley Periodicals, Inc.     

Multifaceted applications of nanomaterials in cell engineering and therapy

Nanomaterials with superior physiochemical properties have been rapidly developed and integrated in every aspect of cell engineering and therapy for translating their great promise to clinical success. Here we demonstrate the multifaceted roles played by innovatively-designed nanomaterials in addressing key challenges in cell engineering and therapy such as cell isolation from heterogeneous cell population, cell instruction in vitro to enable desired functionalities, and targeted cell delivery to therapeutic sites for prompting tissue repair. The emerging trends in this interdisciplinary and dynamic field are also highlighted, where the nanomaterial-engineered cells constitute the basis for establishing in vitro disease model; and nanomaterial-based in situ cell engineering are accomplished directly within the native tissue in vivo. We will witness the increasing importance of nanomaterials in revolutionizing the concept and toolset of cell engineering and therapy which will enrich our scientific understanding of diseases and ultimately fulfill the therapeutic demand in clinical medicine.     

Estrous Cycle‐Dependent Expression of Estrogen Receptor α in Periodontal Tissue

Estrogen receptor α (ERα) may play important roles in many estrogen physiological effects, but little is known about the fluctuation of ERα during the estrous cycle. In this study, the dynamic expression of ERα mRNA and protein in periodontal tissue during the estrous cycle were examined. Forty 12‐week‐old female rats were divided into four groups, based on the estrous cycle stage, and sacrificed. Immunohistochemistry and in situ hybridization were used to detect dynamic changes in ERα protein and mRNA in periodontal tissue during the estrous cycle, and data were analyzed by one‐way ANOVA and cosinor analysis for temporal patterns. Significant differences (p<0.05) were found in the expression of ERα protein and mRNA among the four groups. The expression of ERα protein and mRNA exhibited an infradian rhythm with a period of about 120 h (five days). The phase and amplitude differences between ERα protein and mRNA were not significant (p>0.05). The results suggest the expression of ERα is dynamic during the estrous cycle and that in the future chronobiologic methods should be used to study the mechanism of estrogen effect on periodontal tissue.     

Responses of photosynthetic properties and chloroplast ultrastructure of Bryum argenteum from a desert biological soil crust to elevated ultraviolet‐B radiation

Our understanding of plant responses to enhanced ultraviolet‐B (UV‐B) radiation has improved over recent decades. However, research on cryptogams is scarce and it remains controversial whether UV‐B radiation causes changes in physiology related to photosynthesis. To investigate the effects of supplementary UV‐B radiation on photosynthesis and chloroplast ultrastructure in Bryum argenteum Hedw., specimens were cultured for 10 days under four UV‐B treatments (2.75, 3.08, 3.25 and 3.41 W m^–2), simulating depletion of 0% (control), 6%, 9% and 12% of stratospheric ozone at the latitude of Shapotou, a temperate desert area of northwest China. Analyses showed malondialdehyde content significantly increased, whereas chlorophyll (Chl) fluorescence parameters and Chl contents decreased with increased UV‐B intensity. These results corresponded with changes in thylakoid protein complexes and chloroplast ultrastructure. Overall, enhanced UV‐B radiation leads to significant decreases in photosynthetic function and serious destruction of the chloroplast ultrastructure of B. argenteum. The degree of negative influences increased with the intensity of UV‐B radiation. These results may not only provide a potential mechanism for supplemental UV‐B effects on photosynthesis of moss crust, but also establish a theoretical basis for further studies of adaptation and response mechanisms of desert ecosystems under future ozone depletion.     

MAIGO2 is involved in abscisic acid‐mediated response to abiotic stresses and Golgi‐to‐ER retrograde transport

The central role of multisubunit tethering complexes in intracellular trafficking has been established in yeast and mammalian systems. However, little is known about their roles in the stress responses and the early secretory pathway in Arabidopsis. In this study, Maigo2 (MAG2), which is equivalent to the yeast Tip20p and mammalian Rad50‐interacting protein, is found to be required for the responses to salt stress, osmotic stress and abscisic acid in seed germination and vegetative growth, and MAG2‐like (MAG2L) is partially redundant with MAG2 in response to environmental stresses. MAG2 strongly interacts with the central region of ZW10, and both proteins are important as plant endoplasmic reticulum (ER)‐stress regulators. ER morphology and vacuolar protein trafficking are unaffected in the mag2, mag2l and zw10 mutants, and the secretory marker to the apoplast is correctly transported in mag2 plants, which indicate that MAG2 functions as a complex with ZW10, and is potentially involved in Golgi‐to‐ER retrograde trafficking. Therefore, a new role for ER–Golgi membrane trafficking in abiotic‐stress and ER‐stress responses is discovered.