Genome-wide microarray analysis of TGFβ signaling in the Drosophila brain

BACKGROUND: Members of TGFβ superfamily are found to play important roles in many cellular processes, such as proliferation, differentiation, development, apoptosis, and cancer. In Drosophila, there are seven ligands that function through combinations of three type I receptors and two type II receptors. These signals can be roughly grouped into two major TGFβ pathways, the dpp/BMP and activin pathways, which signal primarily through thick veins (tkv) and baboon (babo). Few downstream targets are known for either pathway, especially targets expressed in the Drosophila brain. RESULTS: tkv and babo both affect the growth of tissues, but have varying effects on patterning. We have identified targets for the tkv and babo pathways by employing microarray techniques using activated forms of the receptors expressed in the brain. In these experiments, we compare the similarities of target genes of these two pathways in the brain. About 500 of 13,500 examined genes changed expression at 95% confidence level (P < 0.05). Twenty-seven genes are co-regulated 1.5 fold by both the tkv and babo pathways. These regulated genes cluster into various functional groups such as DNA/RNA binding, signal transducers, enzymes, transcription regulators, and neuronal regulators. RNAi knockdown experiments of homologs of several of these genes show abnormal growth regulation, suggesting these genes may execute the growth properties of TGFβ. CONCLUSIONS: Our genomic-wide microarray analysis has revealed common targets for the tkv and babo pathways and provided new insights into downstream effectors of two distinct TGFβ like pathways. Many of these genes are novel and several genes are implicated in growth control. Among the genes regulated by both pathways is ultraspiracle, which further connects TGFβ with neuronal remodeling

Simultaneous real-time visible and infrared video with single-pixel detectors

Conventional cameras rely upon a pixelated sensor to provide spatial resolution. An alternative approach replaces the sensor with a pixelated transmission mask encoded with a series of binary patterns. Combining knowledge of the series of patterns and the associated filtered intensities, measured by single-pixel detectors, allows an image to be deduced through data inversion. In this work we extend the concept of a ‘single-pixel camera’ to provide continuous real-time video at 10 Hz , simultaneously in the visible and short-wave infrared, using an efficient computer algorithm. We demonstrate our camera for imaging through smoke, through a tinted screen, whilst performing compressive sampling and recovering high-resolution detail by arbitrarily controlling the pixel-binning of the masks. We anticipate real-time single-pixel video cameras to have considerable importance where pixelated sensors are limited, allowing for low-cost, non-visible imaging systems in applications such as night-vision, gas sensing and medical diagnostics

Regulation of genes affecting body size and innate immunity by the DBL-1/BMP-like pathway in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>Bone morphogenetic proteins (BMPs) are members of the conserved transforming growth factor β (TGFβ superfamily, and play many developmental and homeostatic roles. In <it>C. elegans</it>, a BMP-like pathway, the DBL-1 pathway, controls body size and is involved in innate immunity. How these functions are carried out, though, and what most of the downstream targets of this pathway are, remain unknown.</p> <p>Results</p> <p>We performed a microarray analysis and compared expression profiles of animals lacking the SMA-6 DBL-1 receptor, which decreases pathway signaling, with animals that overexpress DBL-1 ligand, which increases pathway signaling. Consistent with a role for DBL-1 in control of body size, we find positive regulation by DBL-1 of genes involved in physical structure, protein synthesis and degradation, and metabolism. However, cell cycle genes were mostly absent from our results. We also identified genes in a <it>hedgehog</it>-related pathway, which may comprise a secondary signaling pathway downstream of DBL-1 that controls body size. In addition, DBL-1 signaling up-regulates pro-innate immunity genes. We identified a reporter for DBL-1 signaling, which is normally repressed but is up-regulated when DBL-1 signaling is reduced.</p> <p>Conclusions</p> <p>Our results indicate that body size in <it>C. elegans </it>is controlled in part by regulation of metabolic processes as well as protein synthesis and degradation. This supports the growing body of evidence that suggests cell size is linked to metabolism. Furthermore, this study discovered a possible role for <it>hedgehog</it>-related pathways in transmitting the BMP-like signal from the hypodermis, where the core DBL-1 pathway components are required, to other tissues in the animal. We also identified the up-regulation of genes involved in innate immunity, clarifying the role of DBL-1 in innate immunity. One of the highly regulated genes is expressed at very low levels in wild-type animals, but is strongly up-regulated in Sma/Mab mutants, making it a useful reporter for DBL-1/BMP-like signaling in <it>C. elegans</it>.</p

A fast 3D reconstruction system with a low-cost camera accessory

Photometric stereo is a three dimensional (3D) imaging technique that uses multiple 2D images, obtained from a fixed camera perspective, with different illumination directions. Compared to other 3D imaging methods such as geometry modeling and 3D-scanning, it comes with a number of advantages, such as having a simple and efficient reconstruction routine. In this work, we describe a low-cost accessory to a commercial digital single-lens reflex (DSLR) camera system allowing fast reconstruction of 3D objects using photometric stereo. The accessory consists of four white LED lights fixed to the lens of a commercial DSLR camera and a USB programmable controller board to sequentially control the illumination. 3D images are derived for different objects with varying geometric complexity and results are presented, showing a typical height error of &lt;3 mm for a 50 mm sized object

The F-type 5′ motif of mouse L1 elements: a major class of L1 termini similar to the A-type in organization but unrelated in sequence

It has previously been shown that the L1 family in the mouse (L1Md) contains two alternative 5' ends called the A- and F-type sequences (1,2). We show here that the F-type element is a major class of murine L1 elements and report on the details of organization of the 5' motif of these F-type elements. Although the A- and F-type 5' sequences share no detectable sequence homology the organization of an F-type 5' end is strikingly similar to that of an A-type. That is, the F-type 5' sequences consist of a tandem array of a small number of 206 bp monomers while the A-type 5' motif consists of a tandem array of 208 bp monomers. All of the A-type elements characterized to date have a truncated monomer at the 5' end of the array. Many of the F-type elements are also terminated at the 5' end by a truncated copy but unlike the A-type elements some F-type elements terminate with a monomer which is within a few nucleotides of being complete. In addition the F-type consensus sequence, in contrast to the A-type sequence, shows homology (70%) to the body of the L1Md starting at the position where the monomer joins the rest of the L1 element

C. elegans serine-threonine kinase KIN-29 modulates TGFβ signaling and regulates body size formation

BACKGROUND: In C. elegans there are two well-defined TGFβ-like signaling pathways. The Sma/Mab pathway affects body size morphogenesis, male tail development and spicule formation while the Daf pathway regulates entry into and exit out of the dauer state. To identify additional factors that modulate TGFβ signaling in the Sma/Mab pathway, we have undertaken a genetic screen for small animals and have identified kin-29. RESULTS: kin-29 encodes a protein with a cytoplasmic serine-threonine kinase and a novel C-terminal domain. The kinase domain is a distantly related member of the EMK (ELKL motif kinase) family, which interacts with microtubules. We show that the serine-threonine kinase domain has in vitro activity. kin-29 mutations result in small animals, but do not affect male tail morphology as do several of the Sma/Mab signal transducers. Adult worms are smaller than the wild-type, but also develop more slowly. Rescue by kin-29 is achieved by expression in neurons or in the hypodermis. Interaction with the dauer pathway is observed in double mutant combinations, which have been seen with Sma/Mab pathway mutants. We show that kin-29 is epistatic to the ligand dbl-1, and lies upstream of the Sma/Mab pathway target gene, lon-1. CONCLUSION: kin-29 is a new modulator of the Sma/Mab pathway. It functions in neurons and in the hypodermis to regulate body size, but does not affect all TGFβ outputs, such as tail morphogenesis

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

BACKGROUND: p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. METHODS: p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. RESULTS: p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. CONCLUSION: Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

bantam Is Required for Optic Lobe Development and Glial Cell Proliferation

microRNAs (miRNAs) are small, conserved, non-coding RNAs that contribute to the control of many different cellular processes, including cell fate specification and growth control. Drosophila bantam, a conserved miRNA, is involved in several functions, such as stimulating proliferation and inhibiting apoptosis in the wing disc. Here, we reported the detailed expression pattern of bantam in the developing optic lobe, and demonstrated a new, essential role in promoting proliferation of mitotic cells in the optic lobe, including stem cells and differentiated glial cells. Changes in bantam levels autonomously affected glial cell number and distribution, and non-autonomously affected photoreceptor neuron axon projection patterns. Furthermore, we showed that bantam promotes the proliferation of mitotically active glial cells and affects their distribution, largely through down regulation of the T-box transcription factor, optomotor-blind (omb, Flybase, bifid). Expression of omb can rescue the bantam phenotype, and restore the normal glial cell number and proper glial cell positioning in most Drosophila brains. These results suggest that bantam is critical for maintaining the stem cell pools in the outer proliferation center and glial precursor cell regions of the optic lobe, and that its expression in glial cells is crucial for their proliferation and distribution

Caenorhabditis elegans SMA-10/LRIG Is a Conserved Transmembrane Protein that Enhances Bone Morphogenetic Protein Signaling

Bone morphogenetic protein (BMP) pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP–like receptor signaling. SMA-10 acts genetically in a BMP–like (Sma/Mab) pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4. We cloned sma-10 and show that it has fifteen leucine-rich repeats and three immunoglobulin-like domains, hallmarks of an LRIG subfamily of transmembrane proteins. SMA-10 is required in the hypodermis, where the core Sma/Mab signaling components function. We demonstrate functional conservation of LRIGs by rescuing sma-10(lf) animals with the Drosophila ortholog lambik, showing that SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro. This interaction is evolutionarily conserved, evidenced by LRIG1 binding to vertebrate receptors. We propose a new role for LRIG family members: the positive regulation of BMP signaling by binding both Type I and Type II receptors