Well-Defined Polymeric Double Helices with Solvent-Triggered Destruction from Amphiphilic Hairy-Like Nanoparticles

Fabrication of nanostructures with great complexity and regularity is a topic of intense current interest because of their importance both in fundamental theories and applications. Here we report an interesting finding of the formation of ordered polymeric double helices with precise structures and high stability. These uniform double helices are hierarchically self-assembling results of undulated multicompartment cylinders which formed from primary amphiphilic mixed-shell nanoparticles. Diblock copolymers of P2VN-<i>b</i>-PAA (poly­(vinylnaphthalene)-<i>block</i>-poly­(acrylic acid) and PEO-<i>b</i>-PAA (poly­(ethylene oxide)-<i>block</i>-poly­(acrylic acid)) were noncovalently/electrostatically cross-linked into amphiphilic PEO/P2VN-shelled nanoparticles by 1,6-hexyldiamine in a common solvent DMF. When the common solvent changed into selective ones (water), undulated cylinders were facilely obtained due to their hydrophobic interparticles interactions. After a certain time aging, these undulated cylinders self-organized into finally thermodynamic-stable double helices with complex but regular superstructures. The conditions and processes of assembling were carefully examined through extensive experiments

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

<div><p>Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage.</p></div

Involvement of Stat1 gene in IR-induced feather defects.

<p>(A) RT-PCR and densitometrical quantification showing increased Stat1 expression in the feather follicles. **, p<0.01; ***, p<0.001. (B) Stat1 antibody staining showing nuclear enrichment after IR exposure (T1 samples). (C) Whole-mount view of the feather epithelium after lentiviral-mediated Stat1 over-expression in the feather follicle. In control experiments, a lentivirus carrying GFP was used. (D) H&E analysis of Stat1 over-expressed feather follicle showing abnormal epithelial branching. Samples were collected 2 weeks after virus infection. Bar = 100 µm.</p

Additional file 2: of Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China

Pedigrees, sequencing chromatograms of disease-causing gene related to HSP families in our cohort. Figure S1. Pedigree, sequencing chromatograms of SPAST gene detected in 16 SPG4 families in our cohort. Figure S2. Western blot analysis of novel mutations of SPAST gene in HEK 293T cells. Figure S3. Pedigree, sequencing chromatograms of 6 ADHSP families in our cohort. Figure S4. Pedigree, sequencing chromatograms of CYP7B1 gene detected in 16 unrelated SPG5 families in our cohort. Figure S5. Pedigree, sequencing chromatograms of 5 ARHSP families in our cohort. (DOCX 9157 kb

Association of low race performance with mtDNA haplogroup L3b of Australian thoroughbred horses

<p>Mitochondrial DNA (mtDNA) encodes the genes for respiratory chain sub-units that determine the efficiency of oxidative phosphorylation in mitochondria. The aim of this study was to determine if there were any haplogroups and variants in mtDNA that could be associated with athletic performance of Thoroughbred horses. The whole mitochondrial genomes of 53 maternally unrelated Australian Thoroughbred horses were sequenced and an association study was performed with the competition histories of 1123 horses within their maternal lineages. A horse mtDNA phylogenetic tree was constructed based on a total of 195 sequences (including 142 from previous reports). The association analysis showed that the sample groups with poor racing performance history were enriched in haplogroup L3b (<i>p</i> = .0003) and its sub-haplogroup L3b1a (<i>p</i> = .0007), while those that had elite performance appeared to be not significantly associated with haplogroups G2 and L3a1a1a (<i>p</i> > .05). Haplogroup L3b and L3b1a bear two and five specific variants of which variant T1458C (site 345 in 16s rRNA) is the only potential functional variant. Furthermore, secondary reconstruction of 16s RNA showed considerable differences between two types of 16s RNA molecules (with and without T1458C), indicating a potential functional effect. The results suggested that haplogroup L3b, could have a negative association with elite performance. The T1458C mutation harboured in haplogroup L3b could have a functional effect that is related to poor athletic performance.</p

Analysis of IR-induced defects in feather formation.

<p>(A–B) H&E analysis of feather follicles after IR-exposure at different doses. At 10 Gy, the total epithelial cell number remains unchanged, yet extensive branching abnormality is seen. This is transient and reversible; at T2 (2 days post-IR) the feathers become normal again. At 20 Gy, the feather epithelium is significantly reduced. Heterogeneity in T3 (3 days post-IR) is noticed, with some recovered little while others showed branching epithelium again. Representative examples of 8 follicles examined in each case are shown. (C) Whole-mount prep of feather epithelial branching at T1 (1 day post-IR) showing the disrupted patterning at 10 or 20 Gy. Bar = 100 µm.</p

AG-490 partially rescues IR-induced defects in feather formation.

<p>(A) Statistics of feather morphology after 20 Gy IR exposure and AG-490 rescue. Compared to un-rescued samples shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089234#pone-0089234-g001" target="_blank">Figure 1</a>, the feather morphology was significantly improved (n = 57). (B) Whole-mount view of feather branching and (C) H&E staining showing the improved feather morphology after AG-490 rescue. Epithelial branching was retained at both T1 and T2. (D) Molecular analysis of AG-490 rescue at T1. Notice the reduced nuclear Stat1, similar P53/gama-H2AX, increased PCNA, and reduced TUNEL staining. (E) Statistics of PCNA and (F) TUNEL staining results. **, p<0.01. (G) Summary of IR-responses in the feather follicle. A cytokine/Stat1 cascade disrupts the normal patterning event in the feather epithelium. Bar = 100 µm.</p

Molecular analysis in the feather follicles after IR exposure.

<p>(A) Immunohistochemistry (red) showing P53 activation, gama-H2AX expression, and PARP activation after IR exposure. Cell proliferation is indicated by PCNA staining, and cell apoptosis is monitored by Caspase-3 staining and TUNEL analysis (green). (B–C) Quantification of PCNA staining and TUNEL analysis. Significant decrease in PCNA staining is noticed after 20 Gy treatment, when TUNEL staining is also the most significant. **, p<0.01; ***, p<0.001. (D) RT-PCR analysis of gene expression in the feather follicle. T0, control samples before IR; T1, 1 day post-IR; T2, 2 days post-IR. Bar = 100 µm.</p

Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis

<div><p>Objective</p><p>Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations.</p><p>Methods</p><p>Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected ‘highly verified’ genes were measured by ELISA among our in-house RA cases and controls.</p><p>Results</p><p>A total of 221 RA-associated genes were newly identified by gene-based association study, including 71‘overlapped’, 76 ‘European-specific’ and 74 ‘Asian-specific’ genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 ‘overlapped’ (<i>ABCF1</i>, <i>FLOT1</i>, <i>HLA-F</i>, <i>IER3</i>, <i>TUBB</i>, <i>ZKSCAN4</i>, <i>BTN3A3</i>, <i>HSP90AB1</i>, <i>CUTA</i>, <i>BRD2</i>, <i>HLA-DMA)</i>, 5 ‘European-specific’ <i>(PHTF1</i>, <i>RPS18</i>, <i>BAK1</i>, <i>TNFRSF14</i>, <i>SUOX)</i> and 4 ‘Asian-specific’ (<i>RNASET2</i>, <i>HFE</i>, <i>BTN2A2</i>, <i>MAPK13</i>) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes <i>FLOT1</i> (P value = 1.70E-02) and <i>HLA-DMA</i> (P value = 4.70E-02) in plasma were significantly different in our in-house samples.</p><p>Conclusion</p><p>Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and detected a long list of overlapped or ethnic specific RA genes. The study not only greatly increases our understanding of genetic susceptibility to RA, but also provides important insights into the ethno-genetic homogeneity and heterogeneity of RA in both ethnicities.</p></div

Worm Generator: A System for High-Throughput <i>in Vivo</i> Screening

Large-scale screening of molecules in organisms requires high-throughput and cost-effective evaluating tools during preclinical development. Here, a novel in vivo screening strategy combining hierarchically structured biohybrid triboelectric nanogenerators (HB-TENGs) arrays with computational bioinformatics analysis for high-throughput pharmacological evaluation using Caenorhabditis elegans is described. Unlike the traditional methods for behavioral monitoring of the animals, which are laborious and costly, HB-TENGs with micropillars are designed to efficiently convert animals’ behaviors into friction deformation and result in a contact–separation motion between two triboelectric layers to generate electrical outputs. The triboelectric signals are recorded and extracted to various bioinformation for each screened compound. Moreover, the information-rich electrical readouts are successfully demonstrated to be sufficient to predict a drug’s identity by multiple-Gaussian-kernels-based machine learning methods. This proposed strategy can be readily applied to various fields and is especially useful in in vivo explorations to accelerate the identification of novel therapeutics