B-cell chronic lymphocytic leukemia (B-CLL) is the most common human leukemia in the world. Deregulation of the TCL1 oncogene is a causal event in the pathogenesis of the aggressive form of this disease as was verified by using animal models. To study the mechanism of Tcl1 regulation in CLL, we carried out microRNA expression profiling of three types of CLL: indolent CLL, aggressive CLL, and aggressive CLL showing 11q deletion. We identified distinct microRNA signatures corresponding to each group of CLL. We further determined that Tcl1 expression is regulated by miR-29 and miR-181, two microRNAs differentially expressed in CLL. Expression levels of miR-29 and miR-181 generally inversely correlated with Tcl1 expression in the CLL samples we examined. Our results suggest that Tcl1 expression in CLL is, at least in part, regulated by miR-29 and miR-181 and that these microRNAs may be candidates for therapeutic agents in

Programmed cell death 4 (Pdcd4) is a tumor suppressor protein that interacts with eukaryotic initiation factor 4A and inhibits protein synthesis. Pdcd4 also suppresses the transactivation of activator protein-1 (AP-1)-responsive promoters by c-Jun. The Akt (protein kinase B) serine/ threonine kinase is a key mediator of phosphoinositide 3-kinase pathway involved in the regulation of cell proliferation, survival, and growth.

No abstract

It is hypothesized that colour vision and opponent processing of colour signals in the visual system evolved as a means of overcoming the extremely unfavourable lighting conditions in the natural environment of early vertebrates. The signi¢cant £icker of illumination inherent in the shallow-water environment complicated the visual process in the achromatic case, in particular preventing early detection of enemies. The presence of two spectral classes of photoreceptors and opponent interaction of their signals at a subsequent retinal level allowed elimination of the £icker from the retinal image. This new visual function provided certain advantages concerning reaction times and favoured survival. This assumption explains why the building blocks for colour vision arose so early, i.e. just after the active predatory lifestyle was mastered. The principal functions of colour vision inherent in extant animals required a more complex neural machinery for colour processing and evolved later as the result of a change in visual function favouring colour vision.

Responses of direction-selective (DS) ganglion cells (GCs) were recorded extracellularly from their axon terminals in the superficial layer of the tectum opticum (TO) of immobilized goldfish, Carassius auratus gibelio (Bloch). Directional tuning curves were measured with contrast edges moving in 12 or more different directions across the receptive field (RF). All directional tuning curves had cardioid-like appearance, their acceptance angles amounted to somewhat more than 180 degrees . According to their preferred directions DS GCs proved to comprise three distinct groups, each group containing DS GCs of ON and OFF subtypes approximately in equal quantity. Thus, this gives six physiological types of DS GCs in total. The preferred direction of a DS GC does not depend to some extent on a value of contrast, speed, size, and form of the stimuli. Coincidence in number of preferred directions with number of semicircular canals implies that DS GCs projecting to tectum are involved in some multimodal sensory integration in postural, locomotor, and oculomotor control in the three-dimensional aquatic world. DS neurons of the TO itself respond independently of the sign of stimulus contrast, have enormous receptive fields, and seem likely to collect signals from the retinal DS units of both ON and OFF subtypes with the same preferred direction.

No abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents and young adults. The essential mechanisms underlying osteosarcomagenesis and progression continue to be obscure. MicroRNAs (miRNAs) have far-reaching effects on the cellular biology of development and cancer. We recently reported that unique miRNA signatures associate with the pathogenesis and progression of OS. Of particular interest, we found that higher expression of miR-27a is associated with clinical metastatic disease. We report here that overexpression of miR-27a/miR-27a*, a microRNA pair derived from a single precursor, promotes pulmonary OS metastases formation. By contrast, sequestering miR-27a/miR-27a* by sponge technology suppressed OS cells invasion and metastases formation. miR-27a/miR-27a* directly repressed CBFA2T3 expression among other target genes. We demonstrated that CBFA2T3 is downregulated in majority of OS samples and its over expression significantly attenuated OS metastatic process mediated by miR-27a/miR-27a* underscoring CBFA2T3 functions as a tumor suppressor in OS. These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.

Responses of direction-selective (DS) ganglion cells (GCs) were recorded extracellularly from their axon terminals in the superficial layer of tectum opticum (TO) of immobilized cyprinid fish Carassius gibelio (Bloch, 1782). Excitatory receptive field (ERF) sizes of six types of DS GCs (ON and OFF cells, each of three distinct preferred directions) were evaluated on the basis of four different methods. In Method 1, the ERF width was calculated as a product of duration of spike train, generated in response to contrast edge moving across the ERF in preferred direction, and the velocity of the stimulus movement. The duration of spike train was estimated either as an interval between the first and the last spikes, or on the basis of the width of bell-shaped post-stimulus histogram of spike response according to its standard deviation. More precise size and position of the ERF can be outlined with edges moving in many different directions. So, in Method 2 diameter of the ERF was calculated on the basis of a mean distance of position of spike appearance from the center of ERF. Method 3 - ERF tracing by small contrast spot moving on several parallel tracks allowed estimation of the ERF width by number of spikes along each track and the ERF length by the duration of spike train. When tracing in two mutually orthogonal projections, the method also permitted calculation of the value of the temporal delay in the network from the same experiment. Canonical method (Method 4) used the ERF mapping with contrast spots flickering sequentially in different places of stimulation area. The length, width and orientation of the ERF were evaluated according to the two-dimensional equivalent of the standard deviation for this data set. All applied methods gave consistent estimates of ERF sizes - mean values of ERF sizes for all four procedures ranged between 4 degrees and 4.8 degrees . These angle values corresponded to retinal area of approximately 300 mum. Small ERFs of the fish DS GCs measured in the current study, indicate that the fish DS units should be classified as "fast" DS units, and are most likely involved in the detection of small objects moving in the surrounding environment.