The preprophase band-associated kinesin-14 OsKCH2 is a processive minus-end-directed microtubule motor.

In animals and fungi, cytoplasmic dynein is a processive minus-end-directed motor that plays dominant roles in various intracellular processes. In contrast, land plants lack cytoplasmic dynein but contain many minus-end-directed kinesin-14s. No plant kinesin-14 is known to produce processive motility as a homodimer. OsKCH2 is a plant-specific kinesin-14 with an N-terminal actin-binding domain and a central motor domain flanked by two predicted coiled-coils (CC1 and CC2). Here, we show that OsKCH2 specifically decorates preprophase band microtubules in vivo and transports actin filaments along microtubules in vitro. Importantly, OsKCH2 exhibits processive minus-end-directed motility on single microtubules as individual homodimers. We find that CC1, but not CC2, forms the coiled-coil to enable OsKCH2 dimerization. Instead, our results reveal that removing CC2 renders OsKCH2 a nonprocessive motor. Collectively, these results show that land plants have evolved unconventional kinesin-14 homodimers with inherent minus-end-directed processivity that may function to compensate for the loss of cytoplasmic dynein

Supramolecular hierarchical polyurethane elastomers for thermal and mechanical property optimization

Supramolecular chemical designs that integrate complementary hydrogen bond donor and acceptor complexes in hierarchical polyurethane elastomers are reported. N2,N6-bis(2-hydroxyethyl)pyridine-2,6-dicarboxamide (PDA) and 5,5-bis(3-hydroxypropyl)barbituric acid (BBA) react with 4,4'-methylenediphenyl diisocyanate (MDI) to produce hard segments capable of multiple intermolecular hydrogen bonds in MDI-PDA/BBA-poly(tetramethylene oxide) (PTMO) polyurethanes. The addition of PDA facilitates the formation of a supramolecular complex, and BBA affords greater intersegmental mixing. As a result, these polyurethanes exhibit higher glass transition temperatures (Tg) and greater strain hardening/strengthening under tensile deformation than a microphase-separated MDI-butanediol (BDO)-PTMO analog. Additionally, increased PDA and BBA contents results in up to a 60 °C increase of Tg determined at 1 Hz via DMA relative to those determined by calorimetric measurements via DSC, which is considerably higher than the 15 °C Tg increase observed in the MDI-BDO-PTMO analog. These results highlight a significant interplay between intersegmental mixing and supramolecular hydrogen bond interactions for the design of robust hierarchical elastomers

Post-Layout Simulation Driven Analog Circuit Sizing

Post-layout simulation provides accurate guidance for analog circuit design, but post-layout performance is hard to be directly optimized at early design stages. Prior work on analog circuit sizing often utilizes pre-layout simulation results as the optimization objective. In this work, we propose a post-layout-simulation-driven (post-simulation-driven for short) analog circuit sizing framework that directly optimizes the post-layout simulation performance. The framework integrates automated layout generation into the optimization loop of transistor sizing and leverages a coupled Bayesian optimization algorithm to search for the best post-simulation performance. Experimental results demonstrate that our framework can achieve over 20% better post-layout performance in competitive time than manual design and the method that only considers pre-layout optimization

The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy.

EGFR amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, in vivo growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated in vitro and in intracranial xenograft models. Cells with DM were relatively radio-resistant and used higher glycolytic respiration and lower oxidative phosphorylation in comparison to cells without them. The DM-containing cell was able to restore tumor heterogeneity by mis-segregation of the DM-chromosomes, giving rise to cell subpopulations without them. As a response to IR, DM-containing cells switched their respiration from glycolic metabolism to oxidative phosphorylation and shifted molecular profiles towards that of cells without DM. Irradiated cells with DM showed the capacity to alter their extracellular microenvironment to not only promote invasiveness of the surrounding cells, regardless of DM status, but also to create a pro-angiogenic tumor microenvironment. IR of cells without DM was found primarily to increase extracellular MMP2 activity. Overall, our data suggest that the DM-containing cells of GBM are responsible for tumor recurrence due to their high invasiveness and radio-resistance and the mis-segregation of their DM chromosomes, to give rise to fast-growing cells lacking DM chromosomes

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Analyzing the Local Electronic Structure of Co3_3O4_4 Using 2p3d Resonant Inelastic X-ray Scattering

We present the cobalt 2p3d resonant inelastic X-ray scattering (RIXS) spectra of Co$_3$O$_4$. Guided by multiplet simulation, the excited states at 0.5 and 1.3 eV can be identified as the $^4$T$_2$ excited state of the tetrahedral Co$^{2+}$ and the $^3$T$_{2g}$ excited state of the octahedral Co$^{3+}$, respectively. The ground states of Co$^{2+}$ and Co$^{3+}$ sites are determined to be high-spin $^4$A$_2$(T$_d$) and low-spin $^1$A$_{1g}$(O$_h$), respectively. It indicates that the high-spin Co$^{2+}$ is the magnetically active site in Co$_3$O$_4$. Additionally, the ligand-to-metal charge transfer analysis shows strong orbital hybridization between the cobalt and oxygen ions at the Co$^{3+}$ site, while the hybridization is weak at the Co$^{2+}$ site