Combination Metabolomics Approach for Identifying Endogenous Substrates of Carnitine/Organic Cation Transporter OCTN1

Purpose

Solute carrier SLC22A4 encodes the carnitine/organic cation transporter OCTN1 and is associated with inflammatory bowel disease, although little is known about how this gene is linked to pathogenesis. The aim of the present study was to identify endogenous substrates that are associated with gastrointestinal inflammation.

Methods

HEK293/OCTN1 and mock cells were incubated with colon extracts isolated from dextran sodium sulfate-induced colitis mice; the subsequent cell lysates were mixed with the amino group selective reagent 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), to selectively label OCTN1 substrates. Precursor ion scanning against the fragment ion of APDS was then used to identify candidate OCTN1 substrates.

Results

Over 10,000 peaks were detected by precursor ion scanning; m/z 342 had a higher signal in HEK293/OCTN1 compared to mock cells. This peak was detected as a divalent ion that contained four APDS-derived fragments and was identified as spermine. Spermine concentration in peripheral blood mononuclear cells from octn1 gene knockout mice (octn1^?/?) was significantly lower than in wild-type mice. Lipopolysaccharide-induced gene expression of inflammatory cytokines in peritoneal macrophages from octn1^?/? mice was lower than in wild-type mice.

Conclusions

The combination metabolomics approach can provide a novel tool to identify endogenous substrates of OCTN1.

     

Acculturation,Acculturative Stress,and Depressive Symptoms in International Migrants: A Study with Vietnamese Women in South Korea

Globally, there have been increasing numbers of migrant women; these women are at an increased risk for depressive symptoms. The purpose of this study was to examine the associations among acculturation, acculturative stress and depressive symptoms in Vietnamese women who migrated to South Korea through marriages. We hypothesized that acculturative stress would serve as a mediator in the relationship between acculturation and depressive symptoms. Our findings from surveys with 217 Vietnamese immigrant women showed that the indirect effect of acculturation on depressive symptoms, mediated through acculturative stress [??.15 (.04)], was significant (bias corrected 95% confidence interval for the indirect effect?=???.25, ??.08). Low levels of acculturation increased acculturative stress, which in turn led to the elevated symptoms of depression. Our findings not only illuminate the adaptation processes of international, female migrants but also suggest avenues to protect and promote their mental well-being.     

Work‐related injuries in the Alaska logging industry, 1991‐2014

Background

Although loggers in Alaska are at high risk for occupational injury, no comprehensive review of such injuries has been performed since the mid‐1990s. We investigated work‐related injuries in the Alaska logging industry during 1991‐2014.

Methods

Using data from the Alaska Trauma Registry and the Alaska Occupational Injury Surveillance System, we described fatal and nonfatal injuries by factors including worker sex and age, timing and geographic location of injuries, and four injury characteristics. Annual injury rates and associated 5‐year simple moving averages were calculated.

Results

We identified an increase in the 5‐year simple moving averages of fatal injury rates beginning around 2005. While injury characteristics were largely consistent between the first 14 and most recent 10 years of the investigation, the size of logging companies declined significantly between these periods.

Conclusions

Factors associated with declines in the size of Alaska logging companies might have contributed to the observed increase in fatal injury rates.

     

Cost-effectiveness analysis for the treatment of non-erosive reflux disease

Non-erosive reflux disease(NERD) is a common condition and acid-suppressing agents are the mainstay of treatment. A cost-effectiveness analysis comparing a PPI, lansoprazole (LPZ) and a H2RA, ranitidine (RAN) for the treatment of NERD in Japan was performed using a decision analysis. The time period studied was one month and payer or patient' s perspective was considered. Efficacy data were estimated from a randomized clinical trial. Expected days without symptom (healthy days) were 20 for LPZ 15 mg/day and 16 for RAN 300 mg/day. Direct costs were 4,750 yen for LPZ and 4,358 yen for RAN. Cost-effectiveness ratio (direct costs/healthy days) was 238 yen for LPZ and 272 yen for RAN. Considering the results from a large-scale survey of GERD patients in Japan, the slightly higher price of LPZ was outweighed by its greater efficacy, also from the patient's willingness to pay perspective. Lansoprazole was superior to ranitidine with regard to both efficacy and cost-effectiveness and therefore is the preferred therapeutic agent for treatment of NERD.     

Procedure of endoscopic removal of a gutta-percha point under the maxillary sinus mucosa by using an ultrathin arthroscope

We describe here a procedure of endoscopic removal of a gutta-percha point under the maxillary sinus mucosa by using an ultrathin arthroscope. In this study, a 1.2-mm-diameter ultrathin arthroscope was introduced for observation into the maxillary sinus. The surgical technique is suggested to be a reliable and minimally invasive procedure that provides limited incision and bone removal and respects the integrity of the sinus.     

Is bruxism associated with changes in neural pathways? A systematic review and meta-analysis of clinical studies using neurophysiological techniques

Brain Imaging and Behavior - This study aimed to systematically review the literature to identify clinical studies assessing neuroplasticity changes induced by or associated with bruxism or a...     

Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer

Genes crucial for cancer development can be mutated via various mechanisms, which may reflect the nature of the mutagen. In thyroid papillary carcinomas, mutations of genes coding for effectors along the MAPK pathway are central for transformation. BRAF point mutation is most common in sporadic tumors. By contrast, radiation-induced tumors are associated with paracentric inversions activating the receptor tyrosine kinases RET and NTRK1. We report here a rearrangement of BRAF via paracentric inversion of chromosome 7q resulting in an in-frame fusion between exons 1-8 of the AKAP9 gene and exons 9-18 of BRAF. The fusion protein contains the protein kinase domain and lacks the autoinhibitory N-terminal portion of BRAF. It has elevated kinase activity and transforms NIH3T3 cells, which provides evidence, for the first time to our knowledge, of in vivo activation of an intracellular effector along the MAPK pathway by recombination. The AKAP9-BRAF fusion was preferentially found in radiation-induced papillary carcinomas developing after a short latency, whereas BRAF point mutations were absent in this group. These data indicate that in thyroid cancer, radiation activates components of the MAPK pathway primarily through chromosomal paracentric inversions, whereas in sporadic forms of the disease, effectors along the same pathway are activated predominantly by point mutations.     

Membrane transport mechanisms of choline in human intestinal epithelial LS180 cells

The aim of the present study was to investigate the membrane transport mechanisms of choline using human intestinal epithelial LS180 cells. The mRNA of choline transporter‐like proteins (CTLs) was expressed significantly in LS180 cells, and the rank order was CTL1 > CTL4 > CTL3 > CTL2 > CTL5. In contrast, the mRNA expression of other choline transporters, organic cation transporter (OCT) 1, OCT2 and high‐affinity choline transporter 1 (CHT1), was considerably lower in LS180 cells. Five mm unlabelled choline, hemicolinium‐3 and guanidine, but not tetraethylammonium, inhibited the cellular uptake of 100 µm choline in LS180 cells. The uptake of choline into LS180 cells was virtually Na⁺‐independent. The uptake of choline was significantly decreased by acidification of the extracellular pH; however, it was not increased by alkalization of the extracellular pH. In addition, both acidification and alkalization of intracellular pH decreased the uptake of choline, indicating that the choline uptake in LS180 cells is not stimulated by the outward H⁺ gradient. On the other hand, the uptake of choline was decreased by membrane depolarization along with increasing extracellular K⁺ concentration. In addition, the Na⁺‐independent uptake of choline was saturable, and the K_m value was estimated to be 108 µm . These findings suggest that the uptake of choline into LS180 cells is membrane potential‐dependent, but not outward H⁺ gradient‐dependent. Copyright © 2014 John Wiley & Sons, Ltd.