Please wait a minute...

Frontiers in Biology

  • Cover Illustration

    2015, Vol.10  No.5

    The Beclin 1-Vps34 complex architecture 
    This figure, which is based on Baskaran et al. (2014), summarizes our current structural knowledge on the human class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1), which is composed of the proteins Beclin 1, Vps34, Vps15,and Atg14L. At the centre is the V-shaped 3D reconstruction of the reconstituted human PI3KC3-C1 determined by single-particle electron microscopy (EMDB: EMD-2846), w [Detail] ...

    Table of Contents

, Volume 10 Issue 5

For Selected: View Abstracts Toggle Thumbnails
Functional states of resident vascular stem cells and vascular remodeling
Desiree F. Leach,Mitzi Nagarkatti,Prakash Nagarkatti,Taixing Cui
Front. Biol.. 2015, 10 (5): 387-397.
Abstract   HTML   PDF (507KB)

Recent evidence indicates that different types of vascular stem cells (VSCs) reside within the mural layers of arteries and veins. The precise identities of these resident VSCs are still unclear; generally, postnatal vasculature contains multilineage stem cells and vascular cell lineage-specific progenitor/stem cells which may participate in both vascular repair and lesion formation. However, the underlying mechanism remains poorly understood. In this review, we summarize the potential molecular mechanisms, which may control the quiescence and activation of resident VSCs and highlight a notion that the differential states of resident VSCs are directly linked to vascular repair or lesion formation.

Figures and Tables | References | Related Articles | Metrics
Beclin 1-Vps34 complex architecture: Understanding the nuts and bolts of therapeutic targets
Deanna H. Morris,Calvin K. Yip,Yi Shi,Brian T. Chait,Qing Jun Wang
Front. Biol.. 2015, 10 (5): 398-426.
Abstract   HTML   PDF (1206KB)

Autophagy is an important lysosomal degradation pathway that aids in the maintenance of cellular homeostasis by breaking down and recycling intracellular contents. Dysregulation of autophagy is linked to a growing number of human diseases. The Beclin 1-Vps34 protein-protein interaction network is critical for autophagy regulation and is therefore essential to cellular integrity. Manipulation of autophagy, in particular via modulation of the action of the Beclin 1-Vps34 complexes, is considered a promising route to combat autophagy-related diseases. Here we summarize recent findings on the core components and structural architecture of the Beclin 1-Vps34 complexes, and how these findings provide valuable insights into the molecular mechanisms that underlie the multiple functions of these complexes and for devising therapeutic strategies.

Figures and Tables | References | Related Articles | Metrics
Targeting ERK1/2-calpain 1-NF-κB signal transduction in secondary tissue damage and astrogliosis after spinal cord injury
Xin Xin Yu,Vimala Bondada,Colin Rogers,Carolyn A. Meyer,Chen Guang Yu
Front. Biol.. 2015, 10 (5): 427-438.
Abstract   HTML   PDF (1394KB)

Neuronal damage, glial inflammation, and astrogliosis/astroglial scar formation are major secondary injury mechanisms that are significant contributors to functional deficits after spinal cord injury (SCI). The objectives of the study were to evaluate the distinct roles of ERK2 vs. ERK1/2 and ERK1/2-calpain 1−NF-κB signal transduction in the tissue damage and astrogliosis/astroglial scar formation following SCI in rats. RNAi approaches, pharmacological intervention (U0126), Western blot analysis, immunofluorescence analysis, and histological assessment were used to target ERK1/2-calpain 1-NF-κB signal transduction pathway for neuroprotection. Histological staining analysis demonstrated that selectively reducing pERK2 using ERK2 siRNA, but not inhibition of pERK1/2 with U0126, significantly reduced lesion volume and improved total tissue sparing, white matter sparing, and gray matter sparing in spinal cord two weeks after contusive SCI. An ERK1/2-calpain 1-NF-κB signal transduction pathway was involved in the astroglial scar formation after SCI. Blockade of ERK1/2 by U0126 decreased calpain 1 expression 4 h following SCI. Selective calpain 1 reduction by lentiviral shRNA attenuated astroglial NF-κB activity and astroglial scar formation after SCI in rats. Taken together, these results demonstrate the involvement of individual ERK2 and calpain 1 signaling pathways in tissue damage and astrogliosis/astroglial scar formation in animal models of SCI. Therefore, targeting individual ERK and its downstream signal transduction of calpain 1-NF-κB may provide greater potential as novel therapeutics for minimizing tissue damage and astroglial scar formation following SCI.

Figures and Tables | References | Related Articles | Metrics
Dynamic methylation driven by neuronal activity in hippocampal neurons impacts complex behavior
Anita E. Autry,Megumi Adachi,Lisa M. Monteggia
Front. Biol.. 2015, 10 (5): 439-447.
Abstract   HTML   PDF (390KB)

Epigenetic processes are well-known to play critical roles in learning and memory. Among epigenetic processes, accumulating data suggests that DNA methylation in particular is a critical determinant of learning and memory. In vitro data have suggested that DNA methyltransferase inhibitors can trigger DNA demethylation and subsequent gene expression of the brain-derived neurotrophic factor gene in an activity dependent manner. To examine if these processes occur in vivo, we chronically infused DNMT inhibitors into the hippocampus and examined the impact on behavior. We find that chronic DNMT inhibition in the hippocampus results in increased anxiety-related behavior and deficits in context-dependent fear conditioning accompanied by an increase in BDNF expression. Gene expression changes were blocked by pretreatment with the NMDA receptor antagonist AP5, suggesting that DNMT inhibition enhances gene expression in an activity-dependent manner and that, conversely, the behavior deficits and abnormal gene expression are facilitated by NMDA receptor activity.

Figures and Tables | References | Related Articles | Metrics
Reckoning the SIX1 mutation’s effects in branchio-oto-renal syndrome — A bioinformatics approach
B. Preethi,V. Shanthi,K. Ramanathan
Front. Biol.. 2015, 10 (5): 448-457.
Abstract   HTML   PDF (1606KB)

Branchio-oto-renal syndrome (BOR) is autosomal dominant disorder which generates hearing impairment and kidney failures in affected individuals. The disease genomic maps were drawn back in recent years, demonstrating, missense mutations responsible in disease were located in SIX1, EYA1 and EYA2 genes. We try to uncover molecular biology of the syndrome with bioinformatics perspective, taking SIX1 and EYA2 protein interaction at center point. The study initiated with 23 natural mutations of SIX1 gene. They were first analyzed with prediction servers like SIFT, PolyPhen2, I Mutant, SNPs&GO, PHD-SNP and Panther, to identify their impact on their structural stability and function. Subsequently it narrowed down to seven consistent with our quest. They were analyzed on IUPred disorder prediction server. Later SIX1 and its all mutant proteins were docked with EYA2 protein using GRAMM-X server. The binding affinity of docked structures was analyzed using DFIRE2 algorithm. The results justify the earlier wet laboratory studies and indicate the reason behind them. Finally we summarize that the proven inactivity of all other mutants is due to the structural disorder created by mutations, hence usual molecular interaction is hindered; strangely protein interaction takes place at DNA binding site of SIX1 mutants.

Figures and Tables | References | Related Articles | Metrics
The complete mitogenome of Lamproptera curia (Lepidoptera: Papilionidae) and phylogenetic analyses of Lepidoptera
Xin-Min Qin,Qing-Xin Guan,Hui-Min Li,Yu Zhang,Yu-Ji Liu,Dan-Ni Guo
Front. Biol.. 2015, 10 (5): 458-472.
Abstract   HTML   PDF (1449KB)

The complete mitochondrial genome sequence of Lamproptera curia was determined in the present study. Our findings showed that the mtDNA of L. curia had a typical organization of insect mitochrondrial DNA − being 15277 base pairs in length, it contained 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes, and a control region(CR). The newly determined sequence was used for phylogenetic analyses, together with those of 45 species of Lepidoptera published elsewhere, including sequences of three species of Diptera as outgroups. The phylogenetic trees were constructed using the concatenated amino acid and nucleotide sequences of the 13 protein-coding genes (PCGs) based on the maximum likelihood (ML) and Bayesian inference (BI) methods. Both BI and ML trees revealed a similar topology structure: (((((Bombycoidea+ Geometroidea) + Noctuoide) + Pyraloidea) + (Papilionoidea+ Hesperioidea)) + Tortricoidea). Furthermore, the phylogenetic analyses demonstrated that each of the 16 families belonged to a monophyletic group respectively. The results of molecular phylogeny from the present study were congruent with traditional classification based on morphology but failed to demonstrate the monophyly of Hesperiidae.

Figures and Tables | References | Related Articles | Metrics
7 articles