Racial Microaggressions, Cultural Mistrust, and Mental Health Outcomes Among Asian American College Students

The present study is an empirical investigation of cultural mistrust as a mediator in the association between racial microaggressions and mental health (anxiety, depression, and well-being) in a sample of Asian American college students. In addition, we explored the role of cultural mistrust as a mediator in the association between racial microaggressions and attitudes toward seeking professional help. Asian American participants (N = 156) were recruited from two institutions located in the Pacific Northwest region of the United States. Participants filled out an online survey consisting of measures assessing the study variables. Bootstrapped results indicated that cultural mistrust was a significant mediator in the relation between microaggressions and well-being, such that racial microaggressions was significantly and positively associated with cultural mistrust, which in turn was significantly and inversely related to well-being. Mediation models involving anxiety, depression, and help-seeking attitudes as outcome variables were nonsignificant. The significant mediation finding (microaggressions → mistrust → well-being) has implications for improved understanding of Asian American students’ reactions to modern day racism and how it relates to their sense of well-being

Identification of correlated genetic variants jointly associated with rheumatoid arthritis using ridge regression

Abstract Using the North American Rheumatoid Arthritis Consortium genome-wide association dataset, we applied ridged, multiple least-squares regression to identify genetic variants with apparent unique contributions to variation of anti-cyclic citrullinated peptide (anti-CCP), a newly identified clinical risk factor for development of rheumatoid arthritis. Within a 2.7-Mbp region on chromosome 6 around the well studied HLA-DRB1 locus, ridge regression identified a single-nucleotide polymorphism that was associated with anti-CCP variation when including the additive effects of other single-nucleotide polymorphisms in a multivariable analysis, but that showed only a weak direct association with anti-CCP. This suggests that multivariable methods can be used to identify potentially relevant genetic variants in regions of interest that would be difficult to detect based on direct associations.http://deepblue.lib.umich.edu/bitstream/2027.42/117369/1/12919_2009_Article_2814.pd

Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice

The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH) cells: Bcl6 promotes and Blimp1 inhibits TFH-cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH-cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH-cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice). Our data indicate that Blimp1 does not control TFH-cell differentiation independently of Bcl6. However, a population of T follicular regulatory (TFR) cells developed independently of Bcl6 in dcKO mice. We have also analyzed regulation of IL-10 and PD-1, two genes controlled by both Bcl6 and Blimp1, and observed that Bcl6 regulates both genes independently of Blimp1. We found that Bcl6 positively regulates PD-1 expression by inhibiting the ability of T-bet/Tbx21 to repress Pdcd1 transcription. Our data provide a novel mechanism for positive control of gene expression by Bcl6, and illuminate how Bcl6 and Blimp1 control TFH-cell differentiation

Vertical beaming of wavelength-scale photonic crystal resonators

We report that $> 80$ of the photons generated inside a photonic crystal slab resonator can be funneled within a small divergence angle of $\pm 30^\circ$. The far-field radiation properties of a photonic crystal slab resonant mode are modified by tuning the cavity geometry and by placing a reflector below the cavity. The former method directly shapes the near-field distribution so as to achieve directional and linearly-polarized far-field patterns. The latter modification takes advantage of the interference effect between the original waves and the reflected waves to enhance the energy-directionality. We find that, regardless of the slab thickness, the optimum distance between the slab and the reflector closely equals one wavelength of the resonance under consideration. We have also discussed an efficient far-field simulation algorithm based on the finite-difference time-domain method and the near- to far-field transformation.Comment: 14 pages, 15 figures, submitted to Phys. Rev.

Graded Associations of Blood Lead and Urinary Cadmium Concentrations with Oxidative-Stress–Related Markers in the U.S. Population: Results from the Third National Health and Nutrition Examination Survey

Although oxidative stress has been proposed as a mechanism of lead and cadmium toxicity mostly based on in vitro experiments or animal studies, it is uncertain whether this mechanism is relevant in the pathogenesis of lead- or cadmium-related diseases in the general population with low environmental exposure to lead and cadmium. We examined associations of blood lead and urinary cadmium levels with oxidative stress markers of serum γ-glutamyltransferase (GGT), vitamin C, carotenoids, and vitamin E among 10,098 adult participants in the third U.S. National Health and Nutrition Examination Survey. After adjusting for race, sex, and age (plus serum total cholesterol in the case of serum carotenoids and vitamin E), blood lead and urinary cadmium levels both showed graded associations, positive with serum GGT and inverse with serum vitamin C, carotenoids, and vitamin E (p for trend < 0.01, respectively). These associations were consistently observed among most subgroups: non-Hispanic white, non-Hispanic black, men, women, all age groups, non-drinkers, drinkers, nonsmokers, ex-smokers, current smokers, and body mass index (< 25, 25–29.9, and ≥30). The strong association of blood lead and urinary cadmium levels with oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead- and cadmium-related diseases even among people with low environmental exposure to lead and cadmium

Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected With Staphylococcus aureus

Exposure to Staphylococcus aureus has a variety of outcomes, from asymptomatic colonization to fatal infection. Strong evidence suggests that host genetics play an important role in susceptibility, but the specific host genetic factors involved are not known. The availability of genome-wide single nucleotide polymorphism (SNP) data for inbred Mus musculus strains means that haplotype association mapping can be used to identify candidate susceptibility genes. We applied haplotype association mapping to Perlegen SNP data and kidney bacterial counts from Staphylococcus aureus-infected mice from 13 inbred strains and detected an associated block on chromosome 7. Strong experimental evidence supports the result: a separate study demonstrated the presence of a susceptibility locus on chromosome 7 using consomic mice. The associated block contains no genes, but lies within the gene cluster of the 26-member extended kallikrein gene family, whose members have well-recognized roles in the generation of antimicrobial peptides and the regulation of inflammation. Efficient mixed-model association (EMMA) testing of all SNPs with two alleles and located within the gene cluster boundaries finds two significant associations: one of the three polymorphisms defining the associated block and one in the gene closest to the block, Klk1b11. In addition, we find that 7 of the 26 kallikrein genes are differentially expressed between susceptible and resistant mice, including the Klk1b11 gene. These genes represent a promising set of candidate genes influencing susceptibility to Staphylococcus aureus

In vitro and in vivo assessments of an optimal polyblend composition of polycaprolactone/gelatin nanofibrous scaffolds for Achilles tendon tissue engineering

In this study, we manufactured various ratios of polycaprolactone (PCL)/gelatin (GE) highly aligned electrospun nanofibrous scaffolds (ENs) to investigate the effects of polymer ratio on tenogenic differentiation activity. For biological assessments, the cell proliferation rate was optimal in the PCL/GE (9:1) group. Interestingly, however, the tenogenic differentiation rate was best for the PCL/GE (7:3) group. From our outcomes, we established that a poly-blending mix of PCL/GE (7:3) is a promising ratio for tenogenic differentiation. Thus, our findings may provide for an effective mesh to promote tenogenic differentiation of ENs in future tendon tissue engineering applications.This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (MSIP&MOHW) (No. 2017M3A9E4048170)

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4–1147) days, the median PFS was 100 days (95% confidence interval (CI), 66–128 days), and median OS was 209 days (95% CI, 128–236 days). Patients with chronic GVHD had better survival—median OS 426 days (95% CI, 194–NE days) vs 143 days (95% CI, 114–226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC

Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.

Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to identify genetic determinants of susceptibility to S. aureus, and evaluate their function with regard to S. aureus infection. One QTL region on chromosome 11 containing 422 genes was found to be significantly associated with susceptibility to S. aureus infection. Of these 422 genes, whole genome transcription profiling identified five genes (Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1) that were significantly differentially expressed in a) S. aureus -infected susceptible (A/J) vs. resistant (C57BL/6J) mice and b) humans with S. aureus blood stream infection vs. healthy subjects. Three of these genes (Dcaf7, Dusp3, and Psme3) were down-regulated in susceptible vs. resistant mice at both pre- and post-infection time points by qPCR. siRNA-mediated knockdown of Dusp3 and Psme3 induced significant increases of cytokine production in S. aureus-challenged RAW264.7 macrophages and bone marrow derived macrophages (BMDMs) through enhancing NF-κB signaling activity. Similar increases in cytokine production and NF-κB activity were also seen in BMDMs from CSS11 (C57BL/6J background with chromosome 11 from A/J), but not C57BL/6J. These findings suggest that Dusp3 and Psme3 contribute to S. aureus infection susceptibility in A/J mice and play a role in human S. aureus infection

Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling

<p>Abstract</p> <p>Background</p> <p>Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.</p> <p>Methods</p> <p>To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.</p> <p>Results</p> <p>The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.</p> <p>Conclusions</p> <p>The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.</p