Expression of long non-coding RNA LOC285194 and its prognostic significance in human pancreatic ductal adenocarcinoma

Introduction: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. lncRNA LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of this study was to investigate relationship between LOC285194 expression and clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of lncRNA LOC285194 in human PDAC cells and tissue samples. The association of LOC285194 expression with clinicopathologic features was analyzed. Kaplan-Meier analyses were used to assess survival of patients. Univariate and multivariate analyses were performed using the Cox proportional hazards model to analyze the prognostic significance of LOC285194 expression. Results: Our data showed that the relative level of LOC285194 in PDAC cells was significantly lower than that in normal human pancreatic duct epithelial cell line. Also, the expression of LOC285194 in PDAC tissues was significantly lower than that in adjacent non-tumor tissues. By statistical analyses, low LOC285194 expression was observed to be closely correlated with clinical stage, lymphnode metastasis and liver metastasis. Kaplan-Meier survival analysis revealed that patients with low LOC285194 expression had a poor overall survival compared with the high LOC285194 group (P < 0.05). Univariate and multivariate analyses showed that low LOC285194 expression was an independent poor prognostic factor for PDAC patients. Conclusions: Our data provided the first evidence that reduced LOC285194 in PDAC tissues was correlated with tumor progression, and lncRNA LOC285194 might be a potential molecular biomarker for predicting the prognosis of patients.     

Feasibility and Preliminary Validation of an Online Version of the Ohio State University Traumatic Brain Injury Identification Method

Objective

To test the feasibility and validity of an online version of an established interview designed to determine a lifetime history of traumatic brain injury (TBI).

DNA methylation changes in the placenta are associated with fetal manganese exposure

Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina's HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p = 0.045). 713 loci were associated with Mn exposure (p < 0.0001). Five significantly differentially-methylated (p < 1.3 × 10⁻⁷) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44 g. Our observations suggest a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation.     

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.     

Superior olivary contributions to auditory system plasticity: medial but not lateral olivocochlear neurons are the source of cochleotomy-induced GAP-43 expression in the ventral cochlear nucleus

A unilateral cochlear lesion induces expression of the growth and plasticity-associated protein 43 (GAP-43) in fibers and their varicosities on specific types of postsynaptic profiles in the ventral cochlear nucleus (VCN), suggesting the induction of synaptic remodeling. One candidate population from which GAP-43 might emerge was neurons of the lateral olivocochlear (LOC) system residing in the lateral superior olive (LSO). Upon cochleotomy, these neurons express GAP-43 mRNA and GAP-43 protein. However, retrograde axonal tracing with Fast Blue or biotinylated dextran amine from VCN revealed that the number of 6.8 +/- 1.3 neurons in the whole ipsilateral LSO labeled in normal adult rats was distinctly small and did not rise after cochleotomy. Concluding that LOC neurons cannot be the source of GAP-43 in the VCN, we reinvestigated the pattern of GAP-43 in situ hybridization and found that, after cochleotomy, shell neurons in the regions surrounding the LSO and medial olivocochlear (MOC) neurons in the ventral nucleus of the trapezoid body up-regulated GAP-43 mRNA. We then lesioned these regions by means of stereotaxic injections of kainic acid. Destruction of shell neurons preceding an ipsilateral cochleotomy did not change the emergence of GAP-43 immunoreactivity in the VCN. However, if the contralateral MOC system was lesioned, the rise of GAP-43 immunoreactivity in VCN on the side of the cochleotomy was significantly reduced. We conclude that, after cochlear dysfunction, MOC neurons are the major (if not exclusive) source of synaptic reorganization in the VCN that could possibly entail compensatory activation of the affected ascending auditory pathway.     

LOC387715/HTRA1 polymorphisms,smoking and combined effects on exudative age‐related macular degeneration in a Korean population

Background: This study was to investigate the association of two single nucleotide polymorphisms (SNPs) in LOC387715 and HTRA1 with exudative age‐related macular degeneration (AMD) in a Korean population and the gene–gene and gene–environment interactions in the development of AMD. Methods: We genotyped two SNPs that are located in the LOC387715 locus (rs10490924) and HTRA1 (rs11200638) in 137 cases of exudative AMD and 187 controls. Results: Both two SNPs were significantly associated with AMD (P = 0.0001). Homozygotes for the risk allele at LOC387715 and HTRA1 had a 3.80‐fold and a 4.03‐fold increased risk of exudative AMD, respectively, compared with homozygotes for the wild‐type allele (P = 0.0001). The joint effects for complement factor H (CFH) Y402H and 10q26 variants indicated an increased risk of exudative AMD. The odds ratios (ORs) of AMD for individuals carrying one‐, two‐ and three‐copy risk alleles of CFH Y402H and LOC387715 were 1.08, 3.49 and 3.64, respectively. Also, the combination effect of the CFH Y402H risk alleles with HTRA1 risk alleles was dose‐dependent. The interaction analysis between gene and environmental factors showed that among several factors, smoking synergistically increased the susceptibility of AMD for variants of LOC387715 and HTRA1, with OR 8.33 (3.05–22.74) and OR 8.50 (3.07–23.51), respectively. Conclusion: This study demonstrated the significant association of the 10q26 SNPs (HTRA1 and LOC387715) in an AMD cohort from Korea and was consistent with previous studies from other populations. Also, a statistically significant interaction between genetic and environmental factors was found.     

Abnormal face identity coding in the middle fusiform gyrus of two brain-damaged prosopagnosic patients

We report a functional magnetic resonance imaging (fMRI) adaptation study of two well-described patients, DF and PS, who present face identity recognition impairments (prosopagnosia) following brain-damage. Comparing faces to non-face objects elicited activation in all visual areas of the cortical face processing network that were spared subsequent to brain damage. The common brain lesion in the two patients was in the right inferior occipital cortex, in the territory of the right “occipital face area” (‘OFA’), which strengthens the critical role of this region in processing faces. Despite the lesion to the right ‘OFA’, there was normal range of sensitivity to faces in the right “fusiform face area” (‘FFA’) in both patients, supporting a non-hierarchical model of face processing at the cortical level. At the same time, however, sensitivity to individual face representations, as indicated by release from adaptation to identity, was abnormal in the right ‘FFA’ of both patients. This suggests that the right ‘OFA’ is necessary to individualize faces, perhaps through reentrant interactions with other cortical face sensitive areas. The lateral occipital area (LO) is damaged bilaterally in patient DF, who also shows visual object agnosia. However, in patient PS, in whom LO was spared, sensitivity to individual representations of non-face objects was still found in this region, as in the normal brain, consistent with her preserved object recognition abilities. Taken together, these observations, which fruitfully combine functional imaging and neuropsychology, place strong constraints on the possible functional organization of the cortical areas mediating face processing in the human brain.     

Neural correlates of hemianopic completion across the vertical meridian

Hemianopic completion refers to the perceptual completion of figures located across the vertical meridian in the context of hemianopia, such that one half of the figure falls within the blind hemifield. It can occur whether the figure is itself complete (veridical completion) or incomplete (paracompletion). Psychophysical evidence suggests that this phenomenon may be a constructive one, and may share features with completion phenomena in normal vision. The neural structures mediating hemianopic completion are unknown. Here we studied the neural activity evoked by hemianopic completion using event-related fMRI in an individual (POV) with a large right visual field homonymous hemianopic scotoma due to left occipital damage. Either a large achromatic circular contour straddling the vertical meridian or a semicircular contour within the left hemifield just crossing the vertical meridian was presented to POV on each trial. POV indicated by button press whether he perceived a semicircular contour, a patchy circular contour or a complete circular contour. On trials where he reported perceiving a complete circular contour despite being presented with a semicircular contour (paracompletion), activity was increased in a region of ipsilateral extrastriate cortex (contralateral to the lesion, ipsilateral to the illusory edge of the circle). These results are discussed in the context of illusory contour completion in healthy subjects and more generally in the recovery of function after brain damage.     

年龄相关性黄斑病变易感因子2的研究进展

年龄相关性黄斑变性(AMD)的患病率逐年上升,已成为老年人视力不可逆性丧失的首位原因.随着中国人口老龄化社会的到来,AMD的防治也将更加艰巨,AMD的多方位研究成为目前眼底病的研究热点.AMD是多因素疾病,与年龄、遗传及环境等因素有关,发病机制尚不明确.近年的流行病学研究发现,10号染色体长臂26段( 10q26)出现的多个多态性位点中年龄相关性黄斑病变易感因子2(ARMS2,rs 10490924)是目前报道的黄种人群中AMD的主要危险因素.对ARMS2基因的流行病学、细胞定位及其相关治疗研究进行综述.