Phosphoinositide 3-Kinase Enhancer Regulates Neuronal Dendritogenesis and Survival in Neocortex

Phosphoinositide 3-kinase enhancer (PIKE) binds and enhances phosphatidylinositol 3-kinase (PI3K)/Akt activities. However, its physiological functions in brain have never been explored. Here we show that PIKE is important in regulating the neuronal survival and development of neocortex. During development, enhanced apoptosis is observed in the ventricular zone of PIKE knock-out $(PIKE^{−/−})$ cortex. Moreover, $PIKE^{−/−}$ neurons show reduced dendritic complexity, dendritic branch length, and soma size. These defects are due to the reduced PI3K/Akt activities in $PIKE^{−/−}$ neurons, as the impaired dendritic arborization can be rescued when PI3K/Akt cascade is augmented in vitro or in $PIKE^{−/−}PTEN^{−/−}$ double-knock-out mice. Interestingly, $PIKE^{−/−}$ mice display behavioral abnormality in locomotion and spatial navigation. Because of the diminished PI3K/Akt activities, $PIKE^{−/−}$ neurons are more vulnerable to glutamate- or stroke-induced neuronal cell death. Together, our data established the critical role of PIKE in regulating neuronal survival and development by substantiating the PI3K/Akt pathway

Investigation of the siliceous hydrogel phase formation in glass-ionomer cement paste

The microstructure evolution of a complex glass-ionomer cement (GIC) paste over the first 72 h of the cement setting reaction was investigated by small-angle neutron scattering (SANS) and infrared spectroscopy. GIC is a biocompatible material which is clinically used for dental fillings. In this study, GIC pastes were prepared, following the ISO9917-1:2007 cement preparation method, from medical grade poly(acrylic acid), SiO₂–Al₂O₃–P₂O₅–CaO–CaF₂ -based fluoroaluminosilicate glass and H₂O/D₂O solvent. During the setting reaction, polyacrylic acid attacks the fluoroaluminosilicate glass particles to form a siliceous hydrogel phase, glass core and hydrated polyacrylate matrix. The formation of the siliceous hydrogel structure and cross-linking of polyacrylate chains play important roles to harden the GIC. Infrared spectroscopy was used to identify the formation of the hydrogel phase and cross-linkage in GIC paste. In addition this paper reports SANS measurements for GIC pastes at different contrast conditions (H₂O:D₂O ratio) from the Bilby instrument at the Australian Centre for Neutron Scattering, ANSTO, Australia. The SANS data provide microstructure information for the hydrogel phase in GIC paste over the length scale of 10–5000 Å

Genome Sequencing of the Sweetpotato Whitefly \u3cem\u3eBemisia tabaci\u3c/em\u3e MED/Q

The sweetpotato whitefly Bemisia tabaci is a highly destructive agricultural and ornamental crop pest. It damages host plants through both phloem feeding and vectoring plant pathogens. Introductions of B. tabaci are difficult to quarantine and eradicate because of its high reproductive rates, broad host plant range, and insecticide resistance. A total of 791 Gb of raw DNA sequence from whole genome shotgun sequencing, and 13 BAC pooling libraries were generated by Illumina sequencing using different combinations of mate-pair and pair-end libraries. Assembly gave a final genome with a scaffold N50 of 437 kb, and a total length of 658 Mb. Annotation of repetitive elements and coding regions resulted in 265.0 Mb TEs (40.3%) and 20 786 protein-coding genes with putative gene family expansions, respectively. Phylogenetic analysis based on orthologs across 14 arthropod taxa suggested that MED/Q is clustered into a hemipteran clade containing A. pisum and is a sister lineage to a clade containing both R. prolixus and N. lugens. Genome completeness, as estimated using the CEGMA and Benchmarking Universal Single-Copy Orthologs pipelines, reached 96% and 79%. These MED/Q genomic resources lay a foundation for future \u27pan-genomic\u27 comparisons of invasive vs. noninvasive, invasive vs. invasive, and native vs. exotic Bemisia, which, in return, will open up new avenues of investigation into whitefly biology, evolution, and management

High-Precision, In Vitro Validation of the Sequestration Mechanism for Generating Ultrasensitive Dose-Response Curves in Regulatory Networks

Our ability to recreate complex biochemical mechanisms in designed, artificial systems provides a stringent test of our understanding of these mechanisms and opens the door to their exploitation in artificial biotechnologies. Motivated by this philosophy, here we have recapitulated in vitro the “target sequestration” mechanism used by nature to improve the sensitivity (the steepness of the input/output curve) of many regulatory cascades. Specifically, we have employed molecular beacons, a commonly employed optical DNA sensor, to recreate the sequestration mechanism and performed an exhaustive, quantitative study of its key determinants (e.g., the relative concentrations and affinities of probe and depletant). We show that, using sequestration, we can narrow the pseudo-linear range of a traditional molecular beacon from 81-fold (i.e., the transition from 10% to 90% target occupancy spans an 81-fold change in target concentration) to just 1.5-fold. This narrowing of the dynamic range improves the sensitivity of molecular beacons to that equivalent of an oligomeric, allosteric receptor with a Hill coefficient greater than 9. Following this we have adapted the sequestration mechanism to steepen the binding-site occupancy curve of a common transcription factor by an order of magnitude over the sensitivity observed in the absence of sequestration. Given the success with which the sequestration mechanism has been employed by nature, we believe that this strategy could dramatically improve the performance of synthetic biological systems and artificial biosensors

A Simple Method to Identify the Dominant Fouling Mechanisms during Membrane Filtration Based on Piecewise Multiple Linear Regression

Membrane fouling is a complicated issue in microfiltration and ultrafiltration. Clearly identifying the dominant fouling mechanisms during the filtration process is of great significance for the phased and targeted control of fouling. To this end, we propose a semi-empirical multiple linear regression model to describe flux decline, incorporating the five fouling mechanisms (the first and second kinds of standard blocking, complete blocking, intermediate blocking, and cake filtration) based on the additivity of the permeate volume contributed by different coexisting mechanisms. A piecewise fitting protocol was established to distinguish the fouling stages and find the significant mechanisms in each stage. This approach was applied to a case study of a microfiltration membrane filtering a model foulant solution composed of polysaccharide, protein, and humic substances, and the model fitting unequivocally revealed that the dominant fouling mechanism evolved in the sequence of initial adaptation, fast adsorption followed by slow adsorption inside the membrane pores, and the gradual growth of a cake/gel layer on the membrane surface. The results were in good agreement with the permeate properties (total organic carbon, ultraviolet absorbance, and fluorescence) during the filtration process. This modeling approach proves to be simple and reliable for identifying the main fouling mechanisms during membrane filtration with statistical confidence

Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex

Phosphoinositide 3-kinase enhancer (PIKE) binds and enhances phosphatidylinositol 3-kinase (PI3K)/Akt activities. However, its physiological functions in brain have never been explored. Here we show that PIKE is important in regulating the neuronal survival and development of neocortex. During development, enhanced apoptosis is observed in the ventricular zone of PIKE knock-out (PIKE-/-) cortex. Moreover, PIKE-/-neurons show reduced dendritic complexity, dendritic branch length, and soma size. These defects are due to the reduced PI3K/Akt activities in PIKE-/- neurons, as the impaired dendritic arborization can be rescued when PI3K/Akt cascade is augmented in vitro or in PIKE-/-PTEN-/- double-knock-out mice. Interestingly, PIKE-/- mice display behavioral abnormality in locomotion and spatial navigation. Because of the diminished PI3K/Akt activities, PIKE-/- neurons are more vulnerable to glutamateor stroke-induced neuronal cell death. Together, our data established the critical role of PIKE in regulating neuronal survival and development by substantiating the PI3K/Akt pathway. © 2011 the authors.Link_to_subscribed_fulltex

Clinical outcomes of percutaneous microwave ablation for pulmonary oligometastases from hepatocellular carcinoma: a retrospective, multicenter study

Abstract Background Pulmonary oligometastases are common in hepatocellular carcinoma (HCC), however, the existing therapeutic options have several limitations. This study aimed to assess the safety and efficacy of microwave ablation (MWA) in the treatment of HCC-originating pulmonary oligometastases. Methods A total of 83 patients, comprising 73 males and 10 females with a median age of 57 years, who had pulmonary oligometastases from HCC, underwent MWA treatment at four different medical institutions. Inclusion criteria for patients involved having primary HCC under control and having less than three oligometastases with a maximum diameter of ≤ 5 cm in the unilateral lung or less than five oligometastases with a maximum diameter of ≤ 3 cm in the bilateral lung. A total of 147 tumors were treated with MWA over 116 sessions. The primary endpoints assessed included technical success, treatment efficacy, and local progression rate, while secondary endpoints encompassed complications, clinical outcomes, overall survival (OS), local progression-free survival (LPFS), and prognostic factors. Results The technical success rate for MWA was 100% (116/116 sessions), and the treatment efficacy rate was 82.3% (121/147 tumors). Six months after MWA, the local progression rate was 23.1% (18/147 tumors). Complications were observed in 10.3% (major) and 47.4% (minor) of the 116 sessions, with no cases of ablation-related deaths. The median follow-up period was 21.6 months (range: 5.7–87.8 months). Median OS was 22.0 months, and the 1-, 2-, and 3-year OS rates were 82.6%, 44.5%, and 25.2%, respectively. Median LPFS was 8.5 months. Multivariate Cox regression analysis identified α-fetoprotein (AFP) levels during initial diagnosis and the number of oligometastases as potential independent prognostic factors for OS (p = 0.017 and 0.045, respectively). Conclusion Percutaneous MWA is a safe and effective treatment modality for pulmonary oligometastases originating from HCC

Lab in a Tube: Ultrasensitive Detection of MicroRNAs at the Single-Cell Level and in Breast Cancer Patients Using Quadratic Isothermal Amplification

Through rational design of a functional molecular probe with high sequence specificity that takes advantage of sensitive isothermal amplification with simple operation, we developed a one-pot hairpin-mediated quadratic enzymatic amplification strategy for microRNA (miRNA) detection. Our method exhibits ultrahigh sensitivity toward miR-21 with detection limits of 10 fM at 37 °C and 1 aM at 4 °C, which corresponds to nine strands of miR-21 in a 15 μL sample, and it is capable of distinguishing among miRNA family members. More importantly, the proposed approach is also sensitive and selective when applied to crude extractions from MCF-7 and PC3 cell lines and even patient tissues from intraductal carcinoma and invasive ductal carcinoma of the breast