Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects

<p>Abstract</p> <p>Background</p> <p>Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.</p> <p>Methods</p> <p>Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.</p> <p>Results</p> <p>SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.</p> <p>Conclusions</p> <p>Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.</p

Merkel Cell Carcinoma of the Axilla and Adrenal Gland: A Case Report with Imaging and Pathologic Findings

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. MCC is characterized by a high incidence of locoregional recurrence, and distant metastasis, and often requires short-term follow-up after treatment. In this present paper, we describe a rare case of MCC, which presented as a palpable axillary mass and an incidental adrenal mass, and report on the ultrasonography, computed tomography, and 18F-fluorodeoxyglucose-positron emission tomography findings. The patient underwent surgery and adjuvant radiation therapy. Seven months after the initial diagnosis, distant metastasis was detected during a follow-up examination

Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

<p>Abstract</p> <p>Background</p> <p>Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.</p> <p>Methods</p> <p>The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.</p> <p>Results</p> <p>PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.</p> <p>Conclusions</p> <p>PPC results in apoptosis of 3T3-L1 cells.</p

Measuring Neighborhood Stability

Final project for URSP601: Research Methods (Spring 2016). University of Maryland, College Park.In their work, students made two types of conclusions—about the effectiveness of the measured characteristics in revealing neighborhood stability and about the stability of particular census tracts in the County. Measured Characteristics: Given that housing sales prices and household incomes are higher than average in Howard County, the typical measures of neighborhood stability are not well-suited to the County. In some measures, for example, between the initial Neighborhood Stability Index and the housing price analysis, the majority of the data did not align. Census tracts identified by the Index as stable were identified as unstable in the housing price analysis. Neighborhood Stability in Howard County: The County’s southwestern section, including Columbia, had the greatest concentration of extreme results: both high and low performing tracts. Its north and west sections were more uniform in their distribution, containing both stable and declining housing prices. Between 2000 and 2010, approximately 80% of Howard County experienced increases in average housing sales prices, with 25 census tracts experiencing increases of more than $100,000. Three census tracts, two located in the north of the County and one south of Columbia, showed increases in average housing sales prices of more than$300,000. Only two census tracts showed a decrease in average housing sales prices, with one of those census tracts experiencing an almost $350,000 decrease in average sales price of homes. The census tracts showing high increases in predicted home sales prices are clustered in the southern part of the County and around Columbia. Two are in the southern part of Columbia in the Owen Brown and Greenleaf areas (census tracts 606707 and 606704). Other census tracts with high increases in prices are west of the Patuxent Parkway and east of Columbia toward Waterloo Park. Roughly half of the County, those census tracts north and west of Columbia, exhibit low to moderate changes in sales prices. Only one census tract (601203), located southeast of Columbia, showed a decrease in sales price. Neighborhoods or census tracts directly within and around Columbia show the least stability, especially those census tracts south of Columbia and along the County’s southern border. Given that this pattern has repeatedly resulted in our analyses, we recommend that the County further assess conditions in these census tracts to verify our findings. Although Columbia is often among the top 10 "Best Places to Live," the highest concentration of tracts at risk of decline are within the boundaries of Columbia. Census tract 6067.04 is the bottom-performing tract, is located in Columbia’s Owen Brown Village area a community with some of the most dated housing stock in Columbia that also has crime issues. There are also several tracts at risk of decline in Columbia’s Long Reach Village area where there are plans to revamp the center, which was declared a blight zone by the Howard County Council. Other tracts at risk of decline are in Clarksville, Laurel and Elkridge. However, with the exception of Clarksville, these areas also consist of stable tracts and those experiencing improvement or upgrade.Howard Count

Combined effects of aerobic exercise and 40-Hz light flicker exposure on early cognitive impairments in Alzheimer’s disease of 3×Tg mice

Alzheimer’s disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-mo-old 3×Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3×Tg-AD mouse model. Five-month-old 3×Tg-AD mice performed 12 wk of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, proinflammatory cytokine expression, mitochondrial function, and neuroplasticity were analyzed. Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and proinflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the nontransgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD-associated cognitive impairment

Recurrent Massive Subcutaneous Hemorrhage in Neurofibromatosis Type 1: A Case Report

Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder that has three major features: multiple neural tumors, café-au-lait spots, and pigmented iris hamartomas (Lisch nodules). The purpose of this case report is to advise physicians of the danger associated with the progression of fast-onset massive hemorrhage to hemodynamic instability, which mandates rapid treatment to prevent the development of a life-threatening condition. A 64-yr-old woman with NF-1 was admitted to the Emergency Department (ED) because of a rapidly growing, 10×5×3 cm-sized mass on the left back area. She had previously undergone surgery for a large subcutaneous hematoma, which had developed on her right back area 30 yr before. She became hemodynamically unstable with hypotension during the next 3 hr after admission to ED. Resuscitation and blood transfusion were done, and the hematoma was surgically removed. The mass presented as a subcutaneous, massive hematoma with pathologic findings of neurofibroma. We report a case of NF-1 that presented as recurrent, massive, subcutaneous hemorrhage on the back region combined with hypovolemic shock

Reversible Splenium Lesion of the Corpus Callosum in Hemorrhagic Fever with Renal Failure Syndrome

This is the first case of virus-associated encephalitis/encephalopathy in which the pathogen was Hantaan virus. A 53-yr-old man presented fever, renal failure and a hemorrhagic tendency and he was diagnosed with hemorrhagic fever with renal failure syndrome (HFRS). In the course of his illness, mild neurologic symptoms such as dizziness and confusion developed and magnetic resonance images revealed a reversible lesion in the splenium of the corpus callosum. This case suggests that HFRS patients with neurologic symptoms like dizziness and mental slowing should be considered to have structural brain lesions and to require brain imaging studies

The first generation of a BAC-based physical map of Brassica rapa

<p>Abstract</p> <p>Background</p> <p>The genus <it>Brassica </it>includes the most extensively cultivated vegetable crops worldwide. Investigation of the <it>Brassica </it>genome presents excellent challenges to study plant genome evolution and divergence of gene function associated with polyploidy and genome hybridization. A physical map of the <it>B. rapa </it>genome is a fundamental tool for analysis of <it>Brassica </it>"A" genome structure. Integration of a physical map with an existing genetic map by linking genetic markers and BAC clones in the sequencing pipeline provides a crucial resource for the ongoing genome sequencing effort and assembly of whole genome sequences.</p> <p>Results</p> <p>A genome-wide physical map of the <it>B. rapa </it>genome was constructed by the capillary electrophoresis-based fingerprinting of 67,468 Bacterial Artificial Chromosome (BAC) clones using the five restriction enzyme SNaPshot technique. The clones were assembled into contigs by means of FPC v8.5.3. After contig validation and manual editing, the resulting contig assembly consists of 1,428 contigs and is estimated to span 717 Mb in physical length. This map provides 242 anchored contigs on 10 linkage groups to be served as seed points from which to continue bidirectional chromosome extension for genome sequencing.</p> <p>Conclusion</p> <p>The map reported here is the first physical map for <it>Brassica </it>"A" genome based on the High Information Content Fingerprinting (HICF) technique. This physical map will serve as a fundamental genomic resource for accelerating genome sequencing, assembly of BAC sequences, and comparative genomics between <it>Brassica </it>genomes. The current build of the <it>B. rapa </it>physical map is available at the <it>B. rapa </it>Genome Project website for the user community.</p

Genome-edited HEADING DATE 3a knockout enhances leaf production in Perilla frutescens

Environmental cues regulate the transition of many plants from vegetative to flowering development. Day length, or photoperiod, is one cue that synchronizes flowering by changing seasons. Consequently, the molecular mechanism of flowering control is prominent in Arabidopsis and rice, where essential genes like FLOWERING LOCUS T (FT) homolog, HEADING DATE 3a (Hd3a), have been connected to flowering regulation. Perilla is a nutrient-rich leaf vegetable, and the flowering mechanism remains largely elusive. We identified flowering-related genes under short-day conditions using RNA sequencing to develop an enhanced leaf production trait using the flowering mechanism in the perilla. Initially, an Hd3a-like gene was cloned from the perilla and defined as PfHd3a. Furthermore, PfHd3a is highly rhythmically expressed in mature leaves under short-day and long-day conditions. Ectopic expression of PfHd3a in Atft-1 mutant plants has been shown to complement Arabidopsis FT function, resulting in early flowering. In addition, our genetic approaches revealed that overexpression of PfHd3a in perilla caused early flowering. In contrast, the CRISPR/Cas9 generated PfHd3a-mutant perilla showed significantly late flowering, resulting in approximately 50% leaf production enhancement compared to the control. Our results suggest that PfHd3a plays a vital role in regulating flowering in the perilla and is a potential target for molecular breeding in the perilla