acts in the PLK1-dependent spindle positioning pathway and supports neural development.

Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles.

Cell Cycle-Dependent Tumor Engraftment and Migration Are Enabled by Aurora-A.

Cell-cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell-cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multiparameter imaging of wound closure assays was used to track cell-cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell-cycle indicator.

Halofuginone Synergistically Enhances Anti-Proliferation of Rapamycin in T Cells and Reduces Cytotoxicity of Cyclosporine in Cultured Renal Tubular Epithelial Cells.

Both rapamycin (RAPA) and cyclosporin A (CsA) are commonly used for immunosuppression, however their adverse side effects limit their application. Thus, it is of interest to develop novel means to enhance or preserve the immunosuppressive activity of RAPA or CsA while reducing their toxicity. Halofuginone (HF) has been recently tested as a potential immunosuppressant.

Approaching the Post-Newtonian Regime with Numerical Relativity: A Compact-Object Binary Simulation Spanning 350 Gravitational-Wave Cycles.

We present the first numerical-relativity simulation of a compact-object binary whose gravitational waveform is long enough to cover the entire frequency band of advanced gravitational-wave detectors, such as LIGO, Virgo, and KAGRA, for mass ratio 7 and total mass as low as 45.5M_{⊙}. We find that effective-one-body models, either uncalibrated or calibrated against substantially shorter numerical-relativity waveforms at smaller mass ratios, reproduce our new waveform remarkably well, with a negligible loss in detection rate due to modeling error.

Catalog of 174 binary black hole simulations for gravitational wave astronomy.

This Letter presents a publicly available catalog of 174 numerical binary black hole simulations following up to 35 orbits. The catalog includes 91 precessing binaries, mass ratios up to 8∶1, orbital eccentricities from a few percent to 10(-5), black hole spins up to 98% of the theoretical maximum, and radiated energies up to 11.1% of the initial mass.

Early response assessment to guide management of methicillin-resistant Staphylococcus aureus bloodstream infections with vancomycin therapy.

Background: A subset of vancomycin-treated patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) developed persistent positive blood cultures. Treatment eventually failed.

Methods: A retrospective study was conducted to determine whether early response on day 3 after initiation of vancomycin therapy for MRSA BSI was associated with reduced rates of persistent bacteremia, end-of-treatment failure, and infection-related mortality.

Halofuginone suppresses T cell proliferation by blocking proline uptake and inducing cell apoptosis.

Inactivation of T cells is a widely used strategy for immunosuppression. Halofuginone (HF) is an antiprotozoal agent for treating parasites in veterinary medicine, and has been demonstrated to inhibit collagen type 1 synthesis, T helper 17 cell differentiation and cytokine production in activated T cells. The present study was designed to examine the biological effects of HF against T cell receptor and interleukin (IL)-2 stimulated T cell proliferation.

The primary locus of motor neuron death in an ALS-PDC mouse model.

A mouse model of amyotrophic lateral sclerosis-parkinsonism-dementia complex based on the consumption of cycad seed flour was used to determine whether the observed pathology of motor neuron loss begins in the distal axons or the spinal cord. Assessments of neuromuscular junction integrity and motor neurons were performed at multiple time points. Mice fed cycad pellets performed worse on the wire hang than controls.

Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface.

The diversity of plasma membrane (PM) proteins presents a challenge for the achievement of cargo-specific regulation of endocytosis. Here, we describe a family of proteins in yeast (ARTs, for arrestin-related trafficking adaptors) that function by targeting specific PM proteins to the endocytic system. Two members (Art1 and Art2) of the family were discovered in chemical-genetic screens, and they direct downregulation of distinct amino acid transporters triggered by specific stimuli.

ESCRTing proteins in the endocytic pathway.

The endosomal sorting complex required for transport (ESCRT) machinery is highly conserved and its components have been found in all five major supergroups of eukaryotes. The three ESCRT complexes and associated proteins play critical roles in receptor downregulation, retroviral budding, and other normal and pathological cellular processes. Besides monoubiquitin-dependent protein cargo recognition and sorting, the ESCRT machinery also appears to drive the formation of multivesicular bodies (MVBs).

New component of ESCRT-I regulates endosomal sorting complex assembly.

The endosomal sorting complex required for transport (ESCRT) complexes play a critical role in receptor down-regulation and retroviral budding. Although the crystal structures of two ESCRT complexes have been determined, the molecular mechanisms underlying the assembly and regulation of the ESCRT machinery are still poorly understood. We identify a new component of the ESCRT-I complex, multivesicular body sorting factor of 12 kD (Mvb12), and demonstrate that Mvb12 binds to the coiled-coil domain of the ESCRT-I subunit vacuolar protein sorting 23 (Vps23).

Cobalt catalysts for the alternating copolymerization of propylene oxide and carbon dioxide: combining high activity and selectivity.

Synthetic pathways to (salcy)CoX (salcy = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane; X = halide or carboxylate) complexes are described. Complexes (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, (R,R)-(salcy)CoOAc, and (R,R)-(salcy)CoOBzF(5) (OBzF(5) = pentafluorobenzoate) are highly active catalysts for the living, alternating copolymerization of propylene oxide (PO) and CO(2), yielding poly(propylene carbonate) (PPC) with no detectable byproducts. The PPC generated using these catalyst systems is highly regioregular and has up to 99% carbonate linkages with a narrow molecular weight distribution (MWD).

Multivesicular body sorting: ubiquitin ligase Rsp5 is required for the modification and sorting of carboxypeptidase S.

The multivesicular body (MVB) sorting pathway provides a mechanism for delivering transmembrane proteins into the lumen of the lysosome/vacuole. Recent studies demonstrated that ubiquitin modification acts in cis as a signal for the sorting of cargoes into this pathway. Here, we present results from a genetic selection designed to identify mutants that missort MVB cargoes.

Gas channels for NH(3): proteins from hyperthermophiles complement an Escherichia coli mutant.

Ammonium transport (Amt) proteins appear to be bidirectional channels for NH(3). The amt genes of the hyperthermophiles Aquifex aeolicus and Methanococcus jannaschii complement enteric amtB mutants for growth at 25 nM NH(3) at 37 degrees C. To our knowledge, Amt proteins are the first hyperthermophilic membrane transport proteins shown to be active in a mesophilic bacterium.