Effects of long-term frozen storage on the compositions of free amino acids and nucleotide-related compounds of the coconut crab Birgus latro

This study examined the effects of long-term frozen storage (-20 °C for 5 months) of free amino acids (FAAs) and nucleotide-related compounds (NRCs) in muscle and hepatopancreas of the coconut crab Birgus latro. Although long-term frozen storage had little effect on FAA composition in muscle, the amounts of several FAAs increased in the hepatopancreas that may be the result of protein decomposition during the frozen storage. Long-term storage at -20°C significantly increased the amounts of disodium 5ʹ-inosine monophosphate (IMP) in muscle and hepatopancreas, resulting from the deaminase activity of 5ʹ-adenosine monophosphate (AMP) which deaminates AMP to IMP. Changes in FAAs and NRCs may result in changes in the flavor of muscle and hepatopancreas of frozen stored coconut crabs, both through altered amounts of each substance and synergistic interactions among substances

Chronic Exposure to Low Frequency Noise at Moderate Levels Causes Impaired Balance in Mice

We are routinely exposed to low frequency noise (LFN; below 0.5 kHz) at moderate levels of 60–70 dB sound pressure level (SPL) generated from various sources in occupational and daily environments. LFN has been reported to affect balance in humans. However, there is limited information about the influence of chronic exposure to LFN at moderate levels for balance. In this study, we investigated whether chronic exposure to LFN at a moderate level of 70 dB SPL affects the vestibule, which is one of the organs responsible for balance in mice. Wild-type ICR mice were exposed for 1 month to LFN (0.1 kHz) and high frequency noise (HFN; 16 kHz) at 70 dB SPL at a distance of approximately 10–20 cm. Behavior analyses including rotarod, beam-crossing and footprint analyses showed impairments of balance in LFN-exposed mice but not in non-exposed mice or HFN-exposed mice. Immunohistochemical analysis showed a decreased number of vestibular hair cells and increased levels of oxidative stress in LFN-exposed mice compared to those in non-exposed mice. Our results suggest that chronic exposure to LFN at moderate levels causes impaired balance involving morphological impairments of the vestibule with enhanced levels of oxidative stress. Thus, the results of this study indicate the importance of considering the risk of chronic exposure to LFN at a moderate level for imbalance

Clinicopathological characteristics and treatment strategies in early gastric cancer: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Both endoscopic and surgical approaches are employed in the treatment of early gastric cancer (EGC). The aim of this study was to establish appropriate treatment strategies for early gastric cancer.</p> <p>Methods</p> <p>We retrospectively examined clinicopathological data of EGC patients who had undergone surgery.</p> <p>Results</p> <p>A total of 327 patients (204 males and 123 females, mean age 63.2 years) were eligible for inclusion in the study. The median follow-up period was 31 months. Of 161 mucosal (pT1a) tumors, 87 were mainly undifferentiated and 110 had an undifferentiated component. Four patients with pT1a tumors had lymph node metastases; all these tumors were signet-ring cell carcinomas and were macroscopic type 0-IIc with ulceration, and only one of them had lymphatic invasion. Among patients with submucosal tumors, four of 43 patients with pT1b1 tumors and 37 of 123 patients with pT1b2 tumors had nodal metastases. Lymph node metastases were significantly higher in mixed undifferentiated type group than differentiated type group for both groups, pT1a-pT1b1 (p = 0.0251) and pT1b2 (p = 0.0430) subgroups. Only four of 45 patients with nodal metastases were diagnosed preoperatively by computed tomography (sensitivity 8.9%, specificity 96.2%). Nine patients with pT1b tumors had recurrence after surgery, and died. The sites of initial recurrence were liver, bone, peritoneum, distant nodes, and the surgical anastomosis.</p> <p>Conclusions</p> <p>The incidence of nodal metastases was approximately 5% in undifferentiated type mucosal (pT1a) tumors, and higher in submucosal (pT1b) tumors. The sensitivity of preoperative diagnosis of nodal metastases in EGC using computed tomography was relatively low in this study. Therefore at present surgery with adequate lymphadenectomy should be performed as curative treatment for undifferentiated type EGC.</p

Brain iron homeostasis, the choroid plexus, and localization of iron transport proteins

Maintenance of appropriate iron homeostasis in the brain is important, but the mechanisms involved in brain iron uptake are incompletely understood. Here, we have analyzed where messenger RNAs that encode iron transport proteins are expressed in the brain, using the Allen Brain atlas, and we conclude that several important iron transporters are highly expressed in the choroid plexus. Based on recent estimates of the surface area of the choroid plexus and on MRI imaging studies of manganese uptake in the brain, we propose that the choroid plexus may have a much greater role than has been previously appreciated in brain iron transport

Prion Protein Modulates Cellular Iron Uptake: A Novel Function with Implications for Prion Disease Pathogenesis

Converging evidence leaves little doubt that a change in the conformation of prion protein (PrPC) from a mainly α-helical to a β-sheet rich PrP-scrapie (PrPSc) form is the main event responsible for prion disease associated neurotoxicity. However, neither the mechanism of toxicity by PrPSc, nor the normal function of PrPC is entirely clear. Recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-iron in prion disease pathogenesis. In this report, we provide evidence that PrPC mediates cellular iron uptake and transport, and mutant PrP forms alter cellular iron levels differentially. Using human neuroblastoma cells as models, we demonstrate that over-expression of PrPC increases intra-cellular iron relative to non-transfected controls as indicated by an increase in total cellular iron, the cellular labile iron pool (LIP), and iron content of ferritin. As a result, the levels of iron uptake proteins transferrin (Tf) and transferrin receptor (TfR) are decreased, and expression of iron storage protein ferritin is increased. The positive effect of PrPC on ferritin iron content is enhanced by stimulating PrPC endocytosis, and reversed by cross-linking PrPC on the plasma membrane. Expression of mutant PrP forms lacking the octapeptide-repeats, the membrane anchor, or carrying the pathogenic mutation PrP102L decreases ferritin iron content significantly relative to PrPC expressing cells, but the effect on cellular LIP and levels of Tf, TfR, and ferritin is complex, varying with the mutation. Neither PrPC nor the mutant PrP forms influence the rate or amount of iron released into the medium, suggesting a functional role for PrPC in cellular iron uptake and transport to ferritin, and dysfunction of PrPC as a significant contributing factor of brain iron imbalance in prion disorders

Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer

<p>Abstract</p> <p>Background</p> <p>T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.</p> <p>Methods</p> <p>We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.</p> <p>Results</p> <p>Out of several predicted epitopes, two synthetic peptides, STEAP_281-296and EZH2_95-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP_281-296and EZH2_95-109-reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating <it>in vitro </it>T-cell responses in patients with LC.</p> <p>Conclusions</p> <p>Peptides STEAP_281-296and EZH2_95-109function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.</p

Genetic Background Strongly Modifies the Severity of Symptoms of Hirschsprung Disease, but Not Hearing Loss in Rats Carrying Ednrbsl Mutations

Hirschsprung disease (HSCR) is thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. However, it remains unknown whether the single complete deletion of important HSCR-associated genes is sufficient to result in HSCR disease. In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrbsl mutations. Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4). Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. We found that the same genetic background markedly changed the aganglionosis, but resulted in only slight changes to hearing loss and pigment disorder. This provided the important evidence, in support of previous studies, that different lineages of neural crest-derived cells migrating along with various pathways are regulated by different signal molecules. This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome