Differences in GlycA and lipoprotein particle parameters may help distinguish acute kawasaki disease from other febrile illnesses in children.

BackgroundGlycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses.MethodsNuclear magnetic resonance was used to quantify GlycA and lipoprotein particle classes and subclasses in pediatric subjects with acute KD (n = 75), post-treatment subacute (n = 36) and convalescent (n = 63) KD, as well as febrile controls (n = 48), and age-similar healthy controls (n = 48).ResultsGlycA was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIG-treated subacute and convalescent KD subjects, and healthy children (P <0.0001). Acute KD subjects had increased total and small low density lipoprotein particle numbers (LDL-P) (P <0.0001) and decreased total high density lipoprotein particle number (HDL-P) (P <0.0001) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested (P <0.0001). While GlycA, CRP, erythrocyte sedimentation rate, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses (AUC = 0.789-0.884), the combinations of GlycA and LDL-P (AUC = 0.909) or GlycA and the LDL-P/HDL-P ratio (AUC = 0.910) were best at discerning KD in patients 6-10 days after illness onset.ConclusionsHigh levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients

Exploration of finite dimensional Kac algebras and lattices of intermediate subfactors of irreducible inclusions

We study the four infinite families KA(n), KB(n), KD(n), KQ(n) of finite dimensional Hopf (in fact Kac) algebras constructed respectively by A. Masuoka and L. Vainerman: isomorphisms, automorphism groups, self-duality, lattices of coideal subalgebras. We reduce the study to KD(n) by proving that the others are isomorphic to KD(n), its dual, or an index 2 subalgebra of KD(2n). We derive many examples of lattices of intermediate subfactors of the inclusions of depth 2 associated to those Kac algebras, as well as the corresponding principal graphs, which is the original motivation. Along the way, we extend some general results on the Galois correspondence for depth 2 inclusions, and develop some tools and algorithms for the study of twisted group algebras and their lattices of coideal subalgebras. This research was driven by heavy computer exploration, whose tools and methodology we further describe.Comment: v1: 84 pages, 13 figures, submitted. v2: 94 pages, 15 figures, added connections with Masuoka's families KA and KB, description of K3 in KD(n), lattices for KD(8) and KD(15). v3: 93 pages, 15 figures, proven lattice for KD(6), misc improvements, accepted for publication in Journal of Algebra and Its Application

An analysis of the Lattice QCD spectra for Ds0∗(2317)D^*_{s0}(2317) and Ds1∗(2460)D^*_{s1}(2460)

In this talk I present the results obtained using effective field theories in a finite volume from a reanalysis of lattice data on the $KD^{(*)}$ systems, where bound states of $KD$ and $KD^*$ are found and associated with the states $D^*_{s0}(2317)$ and $D^*_{s1}(2460)$, respectively. We confirm the presence of such states on the lattice data and determine the weight of the $KD$ channel in the wave function of $D^*_{s0}(2317)$ and that of $KD^*$ in the wave function of $D^*_{s1}(2460)$. Our results indicate a large meson-meson component in both cases.Comment: Conference Proceedings, Hadron 2017, Salamanca, Spai

Lifetime cardiovascular management of patients with previous Kawasaki disease.

Kawasaki disease (KD) is an inflammatory disorder of young children, associated with vasculitis of the coronary arteries with subsequent aneurysm formation in up to one-third of untreated patients. Those who develop aneurysms are at life-long risk of coronary thrombosis or the development of stenotic lesions, which may lead to myocardial ischaemia, infarction or death. The incidence of KD is increasing worldwide, and in more economically developed countries, KD is now the most common cause of acquired heart disease in children. However, many clinicians in the UK are unaware of the disorder and its long-term cardiac complications, potentially leading to late diagnosis, delayed treatment and poorer outcomes. Increasing numbers of patients who suffered KD in childhood are transitioning to the care of adult services where there is significantly less awareness and experience of the condition than in paediatric services. The aim of this document is to provide guidance on the long-term management of patients who have vascular complications of KD and guidance on the emergency management of acute coronary complications. Guidance on the management of acute KD is published elsewhere

BPTF Enhances Chemotherapy Induced Cytotoxicity

BPTF Enhances Chemotherapy Induced Cytotoxicity Valentina Posada, Depts. of Biology, Chemistry, & Religious Studies, with Dr. Joseph Landry, Dept. of Human Molecular Genetics New chemotherapies and immunotherapy treatments have greatly improved the outcomes of many cancers. However, for Triple Negative Breast Cancer (TNBC), existing therapies are not very effective long term as the disease becomes resistant and has low immunogenicity. Here we show the early development of a new way to treat the disease by combining existing chemotherapies with depletion of the Nucleosome Remodeling Factor (NURF). NURF is an ATP-dependent chromatin remodeling complex that is over-expressed in cancers and has shown to inhibit the anti-tumor immune response. The largest and essential subunit of the complex, BPTF is required for function. BPTF shRNA-mediated knockdown (KD) was done as a way to deplete cells of NURF. Our first aim was to determine if BPTF-KD cells showed enhanced sensitization to chemotherapies most prominently Doxorubicin. The results from completing this aim showed sensitization to several chemotherapies which correlated with enhanced therapy-induced autophagy. Our second aim was then to investigate the role of autophagy in the sensitization of BPTF-KD cells to chemotherapies. Autophagy is a process by which cells undergoing stress consume their cellular components. This process is mediated in part by the ATG5 protein. ATG5 KD was done through lentivirus transfection, and in turn, functional blockade of autophagy was achieved as confirmed by Western blotting. Results showed that BPTF-KD cells did not have enhanced sensitivity to Doxorubicin through the blockade of autophagy, which suggested a non-protective role in autophagy, while the BPTF-WT cells that had autophagy blocked did show an enhanced sensitization, suggesting a cytoprotective role. Aims were then tested in vivo to determine the role of autophagy in BPTF-KD cells in vivo. BPTF-KD and ATG5-KD 4T1 cells were transplanted into mice and tumor volume over time was measured. Syngeneic mouse models showed that the BPTF-KD tumors had significantly smaller tumor volumes than the control when treated with Doxorubicin, and therefore showed sensitization to Doxorubicin. Results for the ATG5 KD mice show tumors growing better in the WT while growing worse in the KD1/ KD2 mice suggesting that autophagy is required for sensitization of BPTF-KD tumors to Doxorubicin in vivo. The third aim of the project was to determine the possible immune-modulatory consequences of treating BPTF KD cells with chemotherapies. Natural Killer (NK) cells were depleted in mice to see if there would be a change in the sensitization to therapies. Results showed that once we depleted NK cells in mice with a mAb-depletion strategy, the sensitization to Doxorubicin was lost. Furthermore, a metabolomics screening was conducted and reductions in prostaglandin E2 (PGE2) were discovered in the therapy treated BPTF-KD cells. PGE2 is a well know immune suppressive metabolite produced by tumor cells to suppress the anti-tumor immune response. Further results showed PGE2 reductions when autophagy was blocked by ATG5 KD in the BPTF-KD cells. This result could explain the improvements in tumor growth within the mice since PGE2 is a known NK cell inhibitor. Together, these results suggest that NURF could be a therapeutic target for enhancing clinical outcomes in Triple Negative Breast Cancer Patients.https://scholarscompass.vcu.edu/uresposters/1328/thumbnail.jp

Apical endosomes isolated from kidney collecting duct principal cells lack subunits of the proton pumping ATPase.

Endocytic vesicles that are involved in the vasopressin-stimulated recycling of water channels to and from the apical membrane of kidney collecting duct principal cells were isolated from rat renal papilla by differential and Percoll density gradient centrifugation. Fluorescence quenching measurements showed that the isolated vesicles maintained a high, HgCl2-sensitive water permeability, consistent with the presence of vasopressin-sensitive water channels. They did not, however, exhibit ATP-dependent luminal acidification, nor any N-ethylmaleimide-sensitive ATPase activity, properties that are characteristic of most acidic endosomal compartments. Western blotting with specific antibodies showed that the 31- and 70-kD cytoplasmically oriented subunits of the vacuolar proton pump were not detectable in these apical endosomes from the papilla, whereas they were present in endosomes prepared in parallel from the cortex. In contrast, the 56-kD subunit of the proton pump was abundant in papillary endosomes, and was localized at the apical pole of principal cells by immunocytochemistry. Finally, an antibody that recognizes the 16-kD transmembrane subunit of oat tonoplast ATPase cross-reacted with a distinct 16-kD band in cortical endosomes, but no 16-kD band was detectable in endosomes from the papilla. This antibody also recognized a 16-kD band in affinity-purified H+ ATPase preparations from bovine kidney medulla. Therefore, early endosomes derived from the apical plasma membrane of collecting duct principal cells fail to acidify because they lack functionally important subunits of a vacuolar-type proton pumping ATPase, including the 16-kD transmembrane domain that serves as the proton-conducting channel, and the 70-kD cytoplasmic subunit that contains the ATPase catalytic site. This specialized, non-acidic early endosomal compartment appears to be involved primarily in the hormonally induced recycling of water channels to and from the apical plasma membrane of vasopressin-sensitive cells in the kidney collecting duct

In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation.

After growth of gonococci in the presence of cytidine monophospho-N-acetyl-neuraminic acid (CMP-NANA), their 4.5-kD lipooligosaccharide (LOS) component was increased by approximately 400 daltons, whereas the LOS of strains lacking the 4.5-kD component were unaffected. Expression of mAb-defined epitopes on the 4.5-kD component was decreased on LOS of strains grown in CMP-NANA, and treatment of the LOS with neuraminidase reversed this affect. Gonococci incubated with human PMNs also had decreased expression of the 4.5-kD+ epitopes. A detergent extract of gonococci incorporated radiolabeled NANA in the LOS, suggesting the presence of a sialyltransferase in gonococci. Exogenous sialyltransferases also could use LOS as an acceptor

Escape from Cells: Deep Kd-Networks for the Recognition of 3D Point Cloud Models

We present a new deep learning architecture (called Kd-network) that is designed for 3D model recognition tasks and works with unstructured point clouds. The new architecture performs multiplicative transformations and share parameters of these transformations according to the subdivisions of the point clouds imposed onto them by Kd-trees. Unlike the currently dominant convolutional architectures that usually require rasterization on uniform two-dimensional or three-dimensional grids, Kd-networks do not rely on such grids in any way and therefore avoid poor scaling behaviour. In a series of experiments with popular shape recognition benchmarks, Kd-networks demonstrate competitive performance in a number of shape recognition tasks such as shape classification, shape retrieval and shape part segmentation.Comment: Spotlight at ICCV'1

Protein-Protein Affinity Determination by Quantitative FRET Quenching.

The molecular dissociation constant, Kd, is a well-established parameter to quantitate the affinity of protein-protein or other molecular interactions. Recently, we reported the theoretical basis and experimental procedure for Kd determination using a quantitative FRET method. Here we report a new development of Kd determination by measuring the reduction in donor fluorescence due to acceptor quenching in FRET. A new method of Kd determination was developed from the quantitative measurement of donor fluorescence quenching. The estimated Kd values of SUMO1-Ubc9 interaction based on this method are in good agreement with those determined by other technologies, including FRET acceptor emission. Thus, the acceptor-quenched approach can be used as a complement to the previously developed acceptor excitation method. The new methodology has more general applications regardless whether the acceptor is an excitable fluorophore or a quencher. Thus, these developments provide a complete methodology for protein or other molecule interaction affinity determinations in solution