Review article

In eukaryotic cells, the trans-Golgi network (TGN) serves as a platform for secretory cargo sorting and trafficking. In recent years, it has become evident that a complex network of lipid-lipid and lipid-protein interactions contributes to these key functions. This review addresses the role of lipids at the TGN with a particular emphasis on sphingolipids and diacylglycerol. We further highlight how these lipids couple secretory cargo sorting and trafficking for spatiotemporal coordination of protein transport to the plasma membrane

Accuracy of B(E2; 0+ -> 2+) transition rates from intermediate-energy Coulomb excitation experiments

The method of intermediate-energy Coulomb excitation has been widely used to determine absolute B(E2; 0+ -> 2+) quadrupole excitation strengths in exotic nuclei with even numbers of protons and neutrons. Transition rates measured with intermediate-energy Coulomb excitation are compared to their respective adopted values and for the example of 26Mg to the B(E2; 0+ -> 2+) values obtained with a variety of standard methods. Intermediate-energy Coulomb excitation is found to have an accuracy comparable to those of long-established experimental techniques.Comment: to be published in Phys. Rev.

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation

Photophysics of the electronic states S0 and S1 for the coplanar molecular structures of the α,ω-diphenylpolyenes DPH and DPO

Spectroscopy of the monoclinic and orthorhombic crystalline forms of all-trans-diphenylhexatriene (DPH) and all-trans-diphenyloctatetraene (DPO) show absorption and emission bands that do not generate the widely known Stokes shift of the polyene compounds, discovered by Hausser et al. in 1953 and repeatedly studied over the last 60 years. It can be concluded from our study that the crystallization system, whether in a monoclinic or orthorhombic system, does not significantly influence the photophysics of DPH and DPO in the crystal phas

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice

Magneto-Optic Trapping of β-Decaying 38Km, 37K From an On-Line Isotope Separator

A magneto-optic trap (MOT) can provide a well-polarized, backing-free, localized source of radioactive atoms for β-decay experiments. We have trapped approximately 6000 atoms of 38Km ( t1/2 = 0.925s) and 2000 atoms of 37K (1.226 s) produced at the TRIUMF on-line separator TISOL in a vapor-cell MOT. We have measured optical isotope shifts and deduced the nuclear charge radii, which show an unusual lack of change at the neutron number N = 20 shell closure. Plans include a search for scalar contributions to the β+- ν correlation in the 0+→0+ decay of 38Km

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman

Transannular interactions in [2.2] phanes as studied by magnetic resonance and optical spectra

The interaction of π-electrons in [2.2] phanes was studied both experimentally and theoretically. The fluorescence and phosphorescence spectra were measured at liquid helium temperature; in addition, the zero field splitting parameters D and E were determined by ODMR in zero field and by ordinary ESR at X-band. The results for the phanes with two identical aromatic units can be summarized as follows: The rather small reduction of the D and E values of the order of 10% with respect to the monomers indicates, in agreement with the theoretical treatment given in part II, that the two unpaired electrons of the excited triplet state have a high probability to be at a given time in the same half of the molecule. While the fluorescence spectra show the typical behaviour of emission spectra of dimers or excimers, the phosphorescence spectra exhibit some remaining structure. This behaviour which indicates a somewhat weaker coupling among the triplet orbitals as compared to the singlet orbitals can also be understood on the basis of theoretical considerations. For a phane with two different aromatic units the behaviour is found to be more similar to the corresponding aromatic monomer with the lower excited states with some perturbation by the other part of the phase also in agreement with theoretical expectation

Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs.

Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking along the Golgi apparatus. This process is Ca2+-dependent and is required for invasive MDA-MB-231 cell migration as well as for gelatin degradation in primary human macrophages. Our findings emphasize the importance of NUCB1 as an essential component of MMP transport and its overall impact on ECM remodeling. © 2020 Pacheco-Fernandez et al