Hmgcr in the Corpus Allatum Controls Sexual Dimorphism of Locomotor Activity and Body Size via the Insulin Pathway in Drosophila

The insulin signaling pathway has been implicated in several physiological and developmental processes. In mammals, it controls expression of 3-Hydroxy-3-Methylglutaryl CoA Reductase (HMGCR), a key enzyme in cholesterol biosynthesis. In insects, which can not synthesize cholesterol de novo, the HMGCR is implicated in the biosynthesis of juvenile hormone (JH). However, the link between the insulin pathway and JH has not been established. In Drosophila, mutations in the insulin receptor (InR) decrease the rate of JH synthesis. It is also known that both the insulin pathway and JH play a role in the control of sexual dimorphism in locomotor activity. In studies here, to demonstrate that the insulin pathway and HMGCR are functionally linked in Drosophila, we first show that hmgcr mutation also disrupts the sexual dimorphism. Similarly to the InR, HMGCR is expressed in the corpus allatum (ca), which is the gland where JH biosynthesis occurs. Two p[hmgcr-GAL4] lines were therefore generated where RNAi was targeted specifically against the HMGCR or the InR in the ca. We found that RNAi-HMGCR blocked HMGCR expression, while the RNAi-InR blocked both InR and HMGCR expression. Each RNAi caused disruption of sexual dimorphism and produced dwarf flies at specific rearing temperatures. These results provide evidence: (i) that HMGCR expression is controlled by the InR and (ii) that InR and HMGCR specifically in the ca, are involved in the control of body size and sexual dimorphism of locomotor activity

Biliary stenting versus surgical bypass for palliation of periampullary malignancy.

BACKGROUND: Patients with periampullary cancers may not be suitable for curative resection due to locally advanced disease, metastases, or poor health. Biliary stenting and surgical bypass are utilized for symptom control, but the true benefit of one technique over the other is not clear. METHODS: A retrospective analysis of case records was undertaken of patients with periampullary (pancreatic head/uncinate process, distal bile duct, and ampulla of Vater and surrounding duodenum) malignancy treated between June 2004 and June 2010 in a tertiary center by palliative biliary stenting or palliative surgical bypass. RESULTS: Of the 69 patients included in the analysis, combined biliary and gastric bypass was performed on 28, while 41 underwent biliary stent (metallic, n = 39) insertion. Patients undergoing stenting were significantly older and less likely to be offered chemotherapy than those from the surgical bypass group. Overall, there were significantly more complications in the stent insertion group (85 %) than the surgical bypass group (36 %) (p = 0.003). The stent group required significantly more subsequent procedures than the surgical bypass group. Metal stent obstruction occurred in 16 of 39 (41 %) patients, with a median stent patency of 224 days. The overall median survival of patients in this study was 7 months with no significant difference between the groups (p = 0.992). The presence of metastases at presentation was the only independent factor associated with decreased survival. CONCLUSION: There was no survival difference between stenting vs. surgical bypass for palliation of periampullary cancer. There was, however, a high rate of stent occlusion and need for repeat procedures in patients treated by metal stenting, suggesting that stenting may be best suited to patients predicted as having the shortest survival

Relationship between functional magnetic resonance imaging-identified regions and neuronal category selectivity.

Functional magnetic resonance imaging (fMRI) has been used extensively to identify regions in the inferior temporal (IT) cortex that are selective for categories of visual stimuli. However, comparatively little is known about the neuronal responses relative to these fMRI-defined regions. Here, we compared in nonhuman primates the distribution and response properties of IT neurons recorded within versus outside fMRI regions selective for four different visual categories: faces, body parts, objects, and places. Although individual neurons that preferred each of the four categories were found throughout the sampled regions, they were most concentrated within the corresponding fMRI region, decreasing significantly within 1-4 mm from the edge of these regions. Furthermore, the correspondence between fMRI and neuronal distributions was specific to neurons that increased their firing rates in response to the visual stimuli but not to neurons suppressed by visual stimuli, suggesting that the processes associated with inhibiting neuronal activity did not contribute strongly to the fMRI signal in this experiment