Salivary histatin 3 inhibits heat shock cognate protein 70–mediated inflammatory cytokine production through toll–like receptors in human gingival fibroblasts.

Background: Salivary histatins are bioactive peptides related to the innate immune system associated with antimicrobial activities. However, very little is known about the physiological and biological functions of histatins against host cells or their role in oral cell inflammation. Histatin 3 binds to heat shock cognate protein 70 (HSC70,a constitutively expressed heat shock protein (HSP)). It is unclear whether HSC70 is involved in the inflammatory response in oral cells. Injured oral cells release some intracellular proteins including HSC70. It is possible that released HSC70 induces toll-like receptor (TLR) activation, just as extracellular HSP70 (a stress inducible HSP) does, and that histatin 3 affects this process. Therefore, we tested the hypothesis that HSC70 activates TLR signaling and histatin 3 inhibits this activation and inflammatory cytokine production. Methods: A nuclear factor (NF)-κB-dependent luciferase reporter plasmid was transfected into HEK293 cells stably expressing TLR2 with coreceptor CD14 (293-TLR2/CD14 cells) or stably expressing TLR4 with CD14 and the accessory molecule MD2 (293-TLR4/MD2-CD14 cells). The cells were stimulated with HSC70 in the presence or absence of histatin 3, and examined using luciferase assays. We also stimulated human gingival fibroblasts (HGFs) with HSC70 with or without histatin 3. Then, we analyzed the levels of inflammatory cytokines (interleukin (IL)-6 and IL-8) in the culture media. Cell proteins were analyzed using enzyme-linked immunosorbent assay and Western blotting with antibodies of mitogen-activated protein kinases and NF-κB inhibitor IκB-α, respectively. Histatin 3-bound form of HSC70 was analyzed using limited V8 protease proteolysis. Results: HSC70 induced NF-κB activation in a dose-dependent manner in 293-TLR2/CD14 and 293-TLR4/MD2-CD14 cells, and histatin 3 inhibited this process and when histatin 3 binding to HSC70 was precluded by 15-deoxyspergualin, which augmented NF-κB-triggered activation. In HGFs, histatin 3 also inhibited HSC70-induced inflammatory cytokine production, extracellular signal-regulated protein kinase phosphorylation, and degradation of IκB-α. Moreover, HSC70 inthe presence of histatin 3 was relatively resistant to digestion by V8 protease compared with HSC70 in the presence of control peptide. Conclusions: Histatin 3 may be an inhibitor of HSC70-triggered activation of TLR signaling and inflammatory cytokine production and may be involved in inflammation processes noted in oral cells

Learning with Biased Complementary Labels

In this paper, we study the classification problem in which we have access to easily obtainable surrogate for true labels, namely complementary labels, which specify classes that observations do \textbf{not} belong to. Let $Y$ and $\bar{Y}$ be the true and complementary labels, respectively. We first model the annotation of complementary labels via transition probabilities $P(\bar{Y}=i|Y=j), i\neq j\in\{1,\cdots,c\}$, where $c$ is the number of classes. Previous methods implicitly assume that $P(\bar{Y}=i|Y=j), \forall i\neq j$, are identical, which is not true in practice because humans are biased toward their own experience. For example, as shown in Figure 1, if an annotator is more familiar with monkeys than prairie dogs when providing complementary labels for meerkats, she is more likely to employ "monkey" as a complementary label. We therefore reason that the transition probabilities will be different. In this paper, we propose a framework that contributes three main innovations to learning with \textbf{biased} complementary labels: (1) It estimates transition probabilities with no bias. (2) It provides a general method to modify traditional loss functions and extends standard deep neural network classifiers to learn with biased complementary labels. (3) It theoretically ensures that the classifier learned with complementary labels converges to the optimal one learned with true labels. Comprehensive experiments on several benchmark datasets validate the superiority of our method to current state-of-the-art methods.Comment: ECCV 2018 Ora

Achieving Stable Nitritation for Mainstream Deammonification by Combining Free Nitrous Acid-Based Sludge Treatment and Oxygen Limitation.

Stable nitritation is a critical bottleneck for achieving autotrophic nitrogen removal using the energy-saving mainstream deammonification process. Herein we report a new strategy to wash out both the Nitrospira sp. and Nitrobacter sp. from the treatment of domestic-strength wastewater. The strategy combines sludge treatment using free nitrous acid (FNA) with dissolved oxygen (DO) control in the nitritation reactor. Initially, the nitrifying reactor achieved full conversion of NH4(+) to NO3(-). Then, nitrite accumulation at ~60% was achieved in the reactor when 1/4 of the sludge was treated daily with FNA at 1.82 mg N/L in a side-stream unit for 24 h. Fluorescence in-situ hybridization (FISH) revealed FNA treatment substantially reduced the abundance of nitrite oxidizing bacteria (NOB) (from 23.0 ± 4.3 to 5.3 ± 1.9%), especially that of Nitrospira sp. (from 15.7 ± 3.9 to 0.4 ± 0.1%). Nitrite accumulation increased to ~80% when the DO concentration in the mainstream reactor was reduced from 2.5-3.0 to 0.3-0.8 mg/L. FISH revealed the DO limitation further reduced the abundance of NOB (to 2.1 ± 1.0%), especially that of Nitrobacter sp. (from 4.9 ± 1.2 to 1.8 ± 0.8%). The strategy developed removes a major barrier for deammonification in low-strength domestic wastewater

Bone marrow uptake of indolent non-Hodgkin lymphoma on PET/CT with histopathological correlation

postprin

Mild hypoxic-ischemic injury in the neonatal rat brain: longitudinal evaluation of the white matter using diffusion tensor MR imaging

Session 75: Perfusion & Diffusion: Animal Models - Oral presentationWe evaluated longitudinally mild hypoxic-ischemic (HI) induced white matter (WM) damage in a neonatal rat model using DTI and correlated the DTI indices with histological evaluations. Results showed significantly decreased FA and increased ¦Ë¡Í in the injured WM reflected dysmyelination. The longitudinal changes of increasing FA, decreasing ¦Ë¡Í, and no change in ¦Ë// in both injured and control WM suggests continued myelination. Furthermore, differences in FA and ¦Ë¡Í between injured and control WM decreased longitudinally. Our results demonstrated that mild HI induced WM damage continues to mature with partial recovery post-HI, and this could be reflected by DTI in vivo.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 74

Mild hypoxic-ischemic injury in the neonatal rat brain: longitudinal evaluation of the white matter using diffusion tensor MR imaging

Session 75: Perfusion & Diffusion: Animal Models - Oral presentationWe evaluated longitudinally mild hypoxic-ischemic (HI) induced white matter (WM) damage in a neonatal rat model using DTI and correlated the DTI indices with histological evaluations. Results showed significantly decreased FA and increased ¦Ë¡Í in the injured WM reflected dysmyelination. The longitudinal changes of increasing FA, decreasing ¦Ë¡Í, and no change in ¦Ë// in both injured and control WM suggests continued myelination. Furthermore, differences in FA and ¦Ë¡Í between injured and control WM decreased longitudinally. Our results demonstrated that mild HI induced WM damage continues to mature with partial recovery post-HI, and this could be reflected by DTI in vivo.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 74

Axial and radial diffusivities as potential markers for characterization of white matter lesions and predicting lesion outcome in a neonatal rat hypoxia-ischemia model

published_or_final_versio

Effects of different doses of melamine in the diet on melamine concentrations in milk, plasma, rumen fluid, urine and feces in lactating dairy cows

The objectives of this paper were to evaluate the effects of feeding diets containing different levels of melamine on melamine concentrations in milk, plasma, rumen fluid, urine and feces in Holstein dairy cows. Sixteen Chinese Holstein dairy cows fixed with permanent ruminal cannulas were assigned to 1 of 4 treatments within a completely randomized design for 10 days. Cows were fed different amounts of melamine {20 (group 1), 40 (group 2), 60 (group 3) or 80 (group 4) g/day/cow} once daily in the morning mixed with a melamine free basal diet for 7-days adaptation followed by 3-days urine and feces sample collections. Melamine was found in all samples tested and its concentration generally increased as dose increased in the diet. These results indicated that different doses of melamine in the diet could result in different concentrations of melamine in milk, plasma, rumen fluid, urine and feces. Data suggested that melamine primarily cleared by urinary excretion, followed by fecal excretion in lactating dairy cows. Mammary tissue was apparently not a major tissue to dispose melamine, especially when fed a relatively low dose (lower than 40 g/day/cow).Key words: Melamine, excretion, lactating dairy cow

Multiple sclerosis susceptibility alleles in African Americans.

Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American data set. EVI5 showed the strongest association outside the major histocompatibility complex (rs10735781, OR=1.233, 95% CI=1.06-1.43, P-value=0.006). In addition, RGS1 seems to affect age of onset whereas TNFRSF1A seems to be associated with disease progression. None of the tested variants showed results that were statistically inconsistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry