Sentinel Node Biopsy for Head and Neck Cutaneous Melanoma

Sentinel lymph node biopsy is the most precise and accurate staging technique for malignant melanoma. This resulted from international collaborations and technical innovations across subspecialties and systematic and methodical study of real-time clinical problems. This article describes sentinel node biopsy from conception to current techniques. Indications for the procedure and evidence of its prognostic value are discussed. Controversies surrounding results of Multicenter Selective Lymphadenectomy Trial I and II and German Dermatologic Cooperative Oncology Group Selective Lymphadenectomy trial are reviewed. Head and neck melanoma is presented as a unique subsite for performing sentinel node biopsy and when considering completion cervical lymphadenectomy

Directed differentiation of notochord-like and nucleus pulposus-like cells using human pluripotent stem cells

Intervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/NODAL and WNT and inhibition of BMP pathways. By day 5 of differentiation, hPSC-derived cells express notochordal cell characteristic genes. After activating the TGF-beta pathway for an additional 15 days, qPCR, immunostaining, and transcriptome data show that a wide array of NP markers are expressed. Transcriptomically, the in vitro-derived cells become more like in vivo adolescent human NP cells, driven by a set of influential genes enriched with motifs bound by BRACHYURY and FOXA2, consistent with an NP cell-like identity. Transplantation of these NP-like cells attenuates fibrotic changes in a rat disc injury model of disc degeneration

2004 Wild Blueberry Project Progress Reports

The 2004 edition of the Wild Blueberry Project Progress Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Determination of Pesticide Residue Levels in Freshly Harvested and Processed Lowbush Blueberries 2. Effect of Wild Blueberry Products on Physical, Chemical, Microbiological and Sensory Quality of Soy-Based and Ground Beef Patties 3. Evaluation of Emerging Disinfection Technologies for Wild Blueberry Processing 4. Detection of Infested Blueberries using Near-Infrared Spectroscopy-Spectra Collection 5. Health Claims for Wild Blueberries 6. Wild blueberries and Arterial Functional Properties 7. Irrigation Water Use in Wild Blueberry Production 8. Insect Control Tactics for Blueberry Pest Insects & Program Base 9. Integrated Pest Management (IPM) Strategies 10. Biology and Ecology of Blueberry Insect Pests 11. Stem Blight/Dieback and Leaf Spot Diseases in Lowbush Blueberry Fields 12. . Evaluation of fungicide control of mummy berry blight in wild blueberries: a) ground application and b) aerial application 13. Effect of Foliar Copper Application on Growth and Yield of Wild Blueberries 14. Effect of Soil pH on Nutrient Uptake 15. Effect of Fertilizer Timing (prune year vs. crop year) on Wild Blueberry Growth and Productivity 16. Raising Foliar Nitrogen by Application of CoRoN 17. Effect of Manganese on Growth and Yield of Wild Blueberry 18. Assessment of Hexazinone Alternatives for Weed Control in Wild Blueberries and Field Cover Program Base 19. Evaluation of Fall Applications of Sulfonylurea Herbicides for Bunchberry Control in Wild Blueberries 20. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 21. Assessment of Evitol for Sedge Control in Wild Blueberries 22. Cultural Weed Management Using pH 23. 2004 Pesticide Groundwater Survey 24. Wild Blueberry Extension Education Program in 200

A Piezoelectric Immunosensor Using Hybrid Self-Assembled Monolayers for Detection of Schistosoma japonicum

BACKGROUND: The parasite Schistosoma japonicum causes schistosomiasis disease, which threatens human life and hampers economic and social development in some Asian countries. An important lesson learned from efforts to reduce the occurrence of schistosomiasis is that the diagnostic approach must be altered as further progress is made towards the control and ultimate elimination of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Using mixed self-assembled monolayer membrane (mixed SAM) technology, a mixture of mercaptopropionic acid (MPA) and mercaptoethanol (ME) was self-assembled on the surface of quartz crystals by gold-sulphur-bonds. Soluble egg antigens (SEA) of S. japonicum were then cross-linked to the quartz crystal using a special coupling agent. As compared with the traditional single self-assembled monolayer immobilization method, S. japonicum antigen (SjAg) immobilization using mixed self-assembled monolayers exhibits much greater immunoreactivity. Under optimal experimental conditions, the detection range is 1:1500 to 1:60 (infected rabbit serum dilution ratios). We measured several infected rabbit serum samples with varying S. japonicum antibody (SjAb) concentrations using both immunosensor and ELISA techniques and then produced a correlation analysis. The correlation coefficients reached 0.973. CONCLUSIONS/SIGNIFICANCE: We have developed a new, simple, sensitive, and reusable piezoelectric immunosensor that directly detects SjAb in the serum. This method may represent an alternative to the current diagnostic methods for S. japonicum infection in the clinical laboratory or for analysis outside the laboratory

Discovery of Shiga Toxin-Producing Escherichia coli (STEC)-Specific Bacteriophages From Non-fecal Composts Using Genomic Characterization

Composting is a complex biodegradable process that converts organic materials into nutrients to facilitate crop yields, and, if well managed, can render bactericidal effects. Majority of research focused on detection of enteric pathogens, such as Shiga toxin-producing Escherichia coli (STEC) in fecal composts. Recently, attention has been emphasized on bacteriophages, such as STEC-specific bacteriophages, associated with STEC from the fecal-contaminated environment because they are able to sustain adverse environmental condition during composting process. However, little is known regarding the isolation of STEC-specific bacteriophages in non-fecal composts. Thus, the objectives were to isolate and genomically characterize STEC-specific bacteriophages, and to evaluate its association with STEC in non-fecal composts. For bacteriophage isolation, the samples were enriched with non-pathogenic E. coli (3 strains) and STEC (14 strains), respectively. After purification, host range, plaque size, and phage morphology were examined. Furthermore, bacteriophage genomes were subjected to whole-genome sequencing using Illumina MiSeq and genomic analyses. Isolation of top six non-O157 and O157 STEC utilizing culture methods combined with PCR-based confirmation was also conducted. The results showed that various STEC-specific bacteriophages, including vB_EcoM-Ro111lw, vB_EcoM-Ro121lw, vB_EcoS-Ro145lw, and vB_EcoM-Ro157lw, with different but complementary host ranges were isolated. Genomic analysis showed the genome sizes varied from 42kb to 149kb, and most bacteriophages were unclassified at the genus level, except vB_EcoM-Ro111lw as FelixO1-like viruses. Prokka predicted less than 25% of the ORFs coded for known functions, including those essential for DNA replication, bacteriophage structure, and host cell lysis. Moreover, none of the bacteriophages harbored lysogenic genes or virulence genes, such as stx or eae. Additionally, the presence of these lytic bacteriophages was likely attributed to zero isolation of STEC and could also contribute to additional antimicrobial effects in composts, if the composting process was insufficient. Current findings indicate that various STEC-specific bacteriophages were found in the non-fecal composts. In addition, the genomic characterization provides in-depth information to complement the deficiency of biological features regarding lytic cycle of the new bacteriophages. Most importantly, these bacteriophages have great potential to control various serogroups of STEC

Combined Analysis of Murine and Human Microarrays and ChIP Analysis Reveals Genes Associated with the Ability of MYC To Maintain Tumorigenesis

The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation, growth, differentiation, self-renewal, and apoptosis. MYC is thought to induce cancer through an exaggerated effect on these physiologic programs. Which of these genes are responsible for the ability of MYC to initiate and/or maintain tumorigenesis is not clear. Previously, we have shown that upon brief MYC inactivation, some tumors undergo sustained regression. Here we demonstrate that upon MYC inactivation there are global permanent changes in gene expression detected by microarray analysis. By applying StepMiner analysis, we identified genes whose expression most strongly correlated with the ability of MYC to induce a neoplastic state. Notably, genes were identified that exhibited permanent changes in mRNA expression upon MYC inactivation. Importantly, permanent changes in gene expression could be shown by chromatin immunoprecipitation (ChIP) to be associated with permanent changes in the ability of MYC to bind to the promoter regions. Our list of candidate genes associated with tumor maintenance was further refined by comparing our analysis with other published results to generate a gene signature associated with MYC-induced tumorigenesis in mice. To validate the role of gene signatures associated with MYC in human tumorigenesis, we examined the expression of human homologs in 273 published human lymphoma microarray datasets in Affymetrix U133A format. One large functional group of these genes included the ribosomal structural proteins. In addition, we identified a group of genes involved in a diverse array of cellular functions including: BZW2, H2AFY, SFRS3, NAP1L1, NOLA2, UBE2D2, CCNG1, LIFR, FABP3, and EDG1. Hence, through our analysis of gene expression in murine tumor models and human lymphomas, we have identified a novel gene signature correlated with the ability of MYC to maintain tumorigenesis

A Regulatory Network for Coordinated Flower Maturation

For self-pollinating plants to reproduce, male and female organ development must be coordinated as flowers mature. The Arabidopsis transcription factors AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8 regulate this complex process by promoting petal expansion, stamen filament elongation, anther dehiscence, and gynoecium maturation, thereby ensuring that pollen released from the anthers is deposited on the stigma of a receptive gynoecium. ARF6 and ARF8 induce jasmonate production, which in turn triggers expression of MYB21 and MYB24, encoding R2R3 MYB transcription factors that promote petal and stamen growth. To understand the dynamics of this flower maturation regulatory network, we have characterized morphological, chemical, and global gene expression phenotypes of arf, myb, and jasmonate pathway mutant flowers. We found that MYB21 and MYB24 promoted not only petal and stamen development but also gynoecium growth. As well as regulating reproductive competence, both the ARF and MYB factors promoted nectary development or function and volatile sesquiterpene production, which may attract insect pollinators and/or repel pathogens. Mutants lacking jasmonate synthesis or response had decreased MYB21 expression and stamen and petal growth at the stage when flowers normally open, but had increased MYB21 expression in petals of older flowers, resulting in renewed and persistent petal expansion at later stages. Both auxin response and jasmonate synthesis promoted positive feedbacks that may ensure rapid petal and stamen growth as flowers open. MYB21 also fed back negatively on expression of jasmonate biosynthesis pathway genes to decrease flower jasmonate level, which correlated with termination of growth after flowers have opened. These dynamic feedbacks may promote timely, coordinated, and transient growth of flower organs

Comparative genetic analysis: the utility of mouse genetic systems for studying human monogenic disease

One of the long-term goals of mutagenesis programs in the mouse has been to generate mutant lines to facilitate the functional study of every mammalian gene. With a combination of complementary genetic approaches and advances in technology, this aim is slowly becoming a reality. One of the most important features of this strategy is the ability to identify and compare a number of mutations in the same gene, an allelic series. With the advent of gene-driven screening of mutant archives, the search for a specific series of interest is now a practical option. This review focuses on the analysis of multiple mutations from chemical mutagenesis projects in a wide variety of genes and the valuable functional information that has been obtained from these studies. Although gene knockouts and transgenics will continue to be an important resource to ascertain gene function, with a significant proportion of human diseases caused by point mutations, identifying an allelic series is becoming an equally efficient route to generating clinically relevant and functionally important mouse models

Energy Response and Longitudinal Shower Profiles Measured in CMS HCAL and Comparison With Geant4

The response of the CMS combined electromagnetic and hadron calorimeter to beams of pions with momenta in the range 5-300 GeV/c has been measured in the H2 test beam at CERN. The raw response with the electromagnetic compartment calibrated to electrons and the hadron compartment calibrated to 300 GeV pions may be represented by sigma = (1.2) sqrt{E} oplus (0.095) E. The fraction of energy visible in the calorimeter ranges from 0.72 at 5 GeV to 0.95 at 300 GeV, indicating a substantial nonlinearity. The intrinsic electron to hadron ratios are fit as a function of energy and found to be in the range 1.3-2.7 for the electromagnetic compartment and 1.4-1.8 for the hadronic compartment. The fits are used to correct the non-linearity of the e pi response to 5% over the entire measured range resulting in a substantially improved resolution at low energy. Longitudinal shower profile have been measured in detail and compared to Geant4 models, LHEP-3.7 and QGSP-2.8. At energies below 30 GeV, the data, LHEP and QGSP are in agreement. Above 30 GeV, LHEP gives a more accurate simulation of the longitudinal shower profile