Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection.National Science Council of Taiwan (100-2321-B-002-007)National Science Council of Taiwan (100-2320-B-002-083-MY3)Taiwan. Ministry of Science and Technology (104-2300-B-002-019-MY3)National Taiwan University. College of Medicine (Translational Medicine Project)National Taiwan University Hospital (101C101-201

Synchronous Ectopic Pancreatoblastoma in a Child: A Case Report

Pancreatoblastoma is a rare primary pancreatic neoplasm of children that may arise in any portion of the pancreas. We report a case of a 3-yr-old boy who presented to with abdominal pain our hospital and a progressive bulge in his right abdomen. Biochemical evaluation and serum levels of tumoral markers were within reference limits. On the computed tomography, two tumors were found. One located in the head of the pancreas; however, a laparotomy revealed that the head of pancreas was compressed but normal. The other was in the left abdomen near the spleen and the tail of the pancreas. The diagnosis of two synchronous pancreatoblastoma originating from the omentum was confirmed by pathology. Therefore, a pancreatoblastoma should be considered when a large well-defined, lobulated, and heterogeneous mass is identified in the pancreas of children. In addition, an ectopic pancreatoblastoma should be considered when identified within or near the ectopic pancreatic tissue

Nonlinear and nonreciprocal transport effects in untwinned thin films of ferromagnetic Weyl metal SrRuO3_3

The identification of distinct charge transport features, deriving from nontrivial bulk band and surface states, has been a challenging subject in the field of topological systems. In topological Dirac and Weyl semimetals, nontrivial conical bands with Fermi-arc surfaces states give rise to negative longitudinal magnetoresistance due to chiral anomaly effect and unusual thickness dependent quantum oscillation from Weyl-orbit effect, which were demonstrated recently in experiments. In this work, we report the experimental observations of large nonlinear and nonreciprocal transport effects for both longitudinal and transverse channels in an untwinned Weyl metal of SrRuO$_3$ thin film grown on a SrTiO$_{3}$ substrate. From rigorous measurements with bias current applied along various directions with respect to the crystalline principal axes, the magnitude of nonlinear Hall signals from the transverse channel exhibits a simple sin$\alpha$ dependent at low temperatures, where $\alpha$ is the angle between bias current direction and orthorhombic [001]$_{\rm o}$, reaching a maximum when current is along orthorhombic [1-10]$_{\rm o}$. On the contrary, the magnitude of nonlinear and nonreciprocal signals in the longitudinal channel attains a maximum for bias current along [001]$_{\rm o}$, and it vanishes for bias current along [1-10]$_{\rm o}$. The observed $\alpha$-dependent nonlinear and nonreciprocal signals in longitudinal and transverse channels reveal a magnetic Weyl phase with an effective Berry curvature dipole along [1-10]$_{\rm o}$ from surface states, accompanied by 1D chiral edge modes along [001]$_{\rm o}$.Comment: 24 pages, 6 figure

Endometrial regenerative cells: A novel stem cell population

Angiogenesis is a critical component of the proliferative endometrial phase of the menstrual cycle. Thus, we hypothesized that a stem cell-like population exist and can be isolated from menstrual blood. Mononuclear cells collected from the menstrual blood contained a subpopulation of adherent cells which could be maintained in tissue culture for >68 doublings and retained expression of the markers CD9, CD29, CD41a, CD44, CD59, CD73, CD90 and CD105, without karyotypic abnormalities. Proliferative rate of the cells was significantly higher than control umbilical cord derived mesenchymal stem cells, with doubling occurring every 19.4 hours. These cells, which we termed "Endometrial Regenerative Cells" (ERC) were capable of differentiating into 9 lineages: cardiomyocytic, respiratory epithelial, neurocytic, myocytic, endothelial, pancreatic, hepatic, adipocytic, and osteogenic. Additionally, ERC produced MMP3, MMP10, GM-CSF, angiopoietin-2 and PDGF-BB at 10–100,000 fold higher levels than two control cord blood derived mesenchymal stem cell lines. Given the ease of extraction and pluripotency of this cell population, we propose ERC as a novel alternative to current stem cells sources

Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms

Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC-driven B cell lymphomas. ARF-BP1 was expressed at high levels in cell lines from lymphomas with either wild type or mutated p53 but not in ARF-deficient cells. Downregulation of ARF-BP1 resulted in elevated steady state levels of p53, growth arrest and apoptosis. Co-immunoprecipitation studies identified a multiprotein complex comprised of ARF-BP1, ARF, p53, MYC and the multifunctional DNA-binding factor, CTCF, which is involved in the transcriptional regulation of MYC, p53 and ARF. ARF-BP1 bound and ubiquitylated CTCF leading to its proteasomal degradation. ARF-BP1 and CTCF thus appear to be key cofactors linking the MYC proliferative and p53-ARF apoptotic pathways. In addition, ARF-BP1 could be a therapeutic target for MYC-driven B lineage neoplasms, even if p53 is inactive, with inhibition reducing the transcriptional activity of MYC for its target genes and stabilizing the apoptosis-promoting activities of p53

Molecular Approaches to Identify Cryptic Species and Polymorphic Species within a Complex Community of Fig Wasps

Cryptic and polymorphic species can complicate traditional taxonomic research and both of these concerns are common in fig wasp communities. Species identification is very difficult, despite great effort and the ecological importance of fig wasps. Herein, we try to identify all chalcidoid wasp species hosted by one species of fig, using both morphological and molecular methods. We compare the efficiency of four different DNA regions and find that ITS2 is highly effective for species identification, while mitochondrial COI and Cytb regions appear less reliable, possibly due to the interference signals from either nuclear copies of mtDNA, i.e. NUMTs, or the effects of Wolbachia infections. The analyses suggest that combining multiple markers is the best choice for inferring species identifications as any one marker may be unsuitable in a given case

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition