MicroRNA-214 functions as an oncogene in human osteosarcoma by targeting TRAF3.

OBJECTIVE: Osteosarcoma is a malignant bone tumor with high incidence. The prognosis of osteosarcoma is very poor when it is diagnosed with metastasis. Numerous studies have demonstrated that aberrant expressions of microRNAs are involved in cancer initiation and development. However, the potential role of miR-214 in osteosarcoma remains largely unrevealed. The current study investigated the relationship between the miR-214 and TNF receptor-associated factor 3 (TRAF3) in osteosarcoma tissues and cell lines. We also aimed to evaluate the potential roles of miR-214 on the occurrence and metastasis in osteosarcoma and verify its effect on the regulation of TRAF3. PATIENTS AND METHODS: The miR-214 expression and TRAF3 expression in osteosarcoma tissue samples and cell line were measured using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Followed by transfection assays, transwell assay was conducted to detect the migration and invasion abilities of osteosarcoma cells. Subsequently, Western blotting and luciferase reporter assay were performed in osteosarcoma cells to confirm the target of miR-214. RESULTS: The results showed that miR-214 expression levels were significantly increased not only in osteosarcoma tissues but also in osteosarcoma cell lines as compared with adjacent normal tissues and matched cell lines, respectively. On the contrary, the TRAF3 expression levels in osteosarcoma tissues and cell lines were frequently decreased compared to the control group. Moreover, TRAF3 was identified as a direct target of miR-214 and the inverse relationship between them was also observed in osteosarcoma tissues. Additionally, we found that miR-214 restoration could significantly promote osteosarcoma cell invasion and migration via targeting TRAF3. CONCLUSIONS: MicroRNA-214 functioned as an oncogene in osteosarcoma via targeting TRAF3, which may provide new insights into osteosarcoma prevention and treatment.

Population delimitation across contrasting evolutionary clines in deer mice (Peromyscus maniculatus).

Despite current interest in population genetics, a concrete definition of a "population" remains elusive. Multiple ecologically and evolutionarily based definitions of population are in current use, which focus, respectively, on demographic and genetic interactions. Accurate population delimitation is crucial for not only evolutionary and ecological population biology, but also for conservation of threatened populations. Along the Pacific Coast of North America, two contrasting patterns of geographic variation in deer mice (Peromyscus maniculatus) converge within the state of Oregon. Populations of these mice diverge morphologically across an east-west axis, and they diverge in mitochondrial DNA haplotypes across a north-south axis. In this study, we investigate these geographically contrasting patterns of differentiation in the context of ecological and evolutionary definitions (paradigms) of populations. We investigate these patterns using a new and geographically expansive sample that integrates data on morphology, mitochondrial DNA, and nuclear DNA. We found no evidence of nuclear genetic differentiation between the morphologically and mitochondrially distinct populations, thus indicating the occurrence of gene flow across Oregon. Under the evolutionary paradigm, Oregon populations can be considered a single population, whereas morphological and mitochondrial differentiations do not indicate distinct populations. In contrast, under the ecological paradigm morphological differentiation indicates distinct populations based on the low likelihood of demographic interactions between geographically distant individuals. The two sympatric but mitochondrially distinct haplogroups form a single population under the ecological paradigm. Hence, we find that the difference between evolutionary and ecological paradigms is the time-scale of interest, and we believe that the more chronologically inclusive evolutionary paradigm may be preferable except in cases where only a single generation is of interest.

Short-latency ocular following in humans is dependent on absolute (rather than relative) binocular disparity.

A previous study showed that the initial ocular following responses elicited by sudden motion of a large random-dot pattern were only modestly attenuated when that whole pattern was shifted out of the plane of fixation by altering its horizontal binocular disparity, but the same disparity applied to a restricted region of the dots had a much more powerful effect [Vision Research 41 (2001) 3371]. Thus, if the dots were partitioned into horizontal bands, for example, and alternate bands were moved in opposite directions to the left or right then ocular following was very weak, but if the (conditioning) dots moving in one direction were all shifted out of the plane of fixation (by applying horizontal disparity to them) then strong ocular following was now seen in the direction of motion of the (test) dots in the plane of fixation, i.e., moving images became much less effective when they were given binocular disparity. We sought to determine if the greater impact of disparity with the partitioned images was because there were additional relative disparity cues. We used a similar partitioned display and found that the dependence of ocular following on the absolute disparity of the conditioning stimulus had a Gaussian form with an x-offset that was close to zero disparity and, importantly, this offset was almost unaffected by changing the absolute disparity of the test stimulus. We conclude from this that it is the absolute--rather than the relative--disparity that is important, and that ocular following has a strong preference for moving images whose absolute disparities are close to zero. This is consistent with the idea that ocular following selectively stabilizes the retinal images of objects in and around the plane of fixation and works in harmony with disparity vergence, which uses absolute disparity to bring objects of interest into the plane of fixation [Archives of Ophthalmology 55 (1956) 848].

Short-latency disparity-vergence eye movements in humans: sensitivity to simulated orthogonal tropias.

Small disparity stimuli applied to large random-dot patterns elicit machine-like vergence eye movements at short latency. We have examined the sensitivity of these eye movements to simulated orthogonal tropias in three normal subjects by recording (1) the effects of vertical disparities on the initial horizontal vergence responses elicited by 2 degrees crossed and uncrossed (horizontal) disparity stimuli, and (2) the effects of horizontal disparities on the initial vertical vergence responses elicited by 1.2 degrees left-hyper and 0.8 degrees right-hyper (vertical) disparity stimuli. Initial vergence responses were strongest when the orthogonal disparity was close to zero, and decreased to zero as the orthogonal disparity increased to 3 degrees -5 degrees, i.e., there was only a limited tolerance for orthogonal disparity. Tuning curves describing the dependence of the initial change in the vergence angle on the orthogonal disparity were well fit by a Gaussian function. An additional subject, who had an esotropia of approximately 10 degrees in our experimental setup, showed almost no horizontal vergence responses but did show vertical vergence responses to vertical disparity stimuli at short latency (albeit slightly longer than normal) despite the fact that her esotropia resulted in uncrossed disparities that would have totally disabled the vertical vergence mechanism of a normal subject, cf., anomalous retinal correspondence.

Version and vergence eye movements in humans: open-loop dynamics determined by monocular rather than binocular image speed.

We examined the velocity dependence of the vergence and version eye movements elicited by motion stimuli that were symmetric or asymmetric at the two eyes. Movements of both eyes were recorded with the scleral search coil technique. Vergence was computed as the difference in the positions of the two eyes (left-right) and version was computed as the average position of the two eyes ((left+right)/2). Subjects faced a large tangent screen onto which two identical random-dot patterns were back-projected. Each pattern was viewed by one eye only using crossed-polarizers and its position was controlled by X/Y mirror galvanometers. Viewing was always binocular and horizontal velocity steps (range, 5-240 deg/s) were applied to one (asymmetric stimulus) or both (symmetric stimulus) patterns approximately 50 ms after a centering saccade. With the symmetric stimulus, the motion at the two eyes could be either in the opposite direction (eliciting vergence responses) or in the same direction (eliciting version responses). The asymmetric stimuli elicited both vergence and version. In all cases, minimum response latencies were very short (<90 ms). Velocity tuning curves (based on the changes in vergence and version over the time period, 90-140 ms) were all sigmoidal and peaked when the monocular (i.e., retinal) image velocities were 30-60 deg/s. The vergence (version) responses to symmetric stimuli were linearly related to the vergence (version) responses to asymmetric stimuli when expressed in terms of the monocular rather than the binocular image velocities. We conclude that the dynamical limits for both vergence and version are imposed in the monocular visual pathways, before the inputs from the two eyes are combined.

Reversed short-latency ocular following.

Using the scleral search coil technique to monitor eye movements, we recorded short-latency ocular following responses to displacement steps of large random-dot patterns. On half of the trials, the luminance of the dots and background were reversed during the step, a procedure that is known to reverse the direction of the perceived motion ("reverse phi"). Steps without luminance reversal induced small but consistent ocular following in the direction of the steps at ultra-short latency (<80 ms). Steps with luminance reversal induced small but consistent tracking at the same latency but in the direction opposite to the actual displacement. Tuning curves describing the dependence of initial ocular following on the amplitude of the displacement had a form approximating the derivative of a Gaussian and were well fit by Gabor functions, the cosine term being phase shifted approximately 180 degrees by the luminance reversal. This result is consistent with the idea that the initial ocular following is mediated, at least in part, by first-order (luminance) motion-energy detectors.