Cryospray ablation (CSA) in the palliative treatment of squamous cell carcinoma of the esophagus

BACKGROUND: Esophageal carcinoma is the ninth most prevalent cancer worldwide with squamous cell carcinoma (SCCA) and adenocarcinoma accounting for the vast majority of new cases (13,900 in 2003). Cure rates in the U.S. are less than 10%, similar to lung cancer. More than 50% of patients with esophageal carcinoma present with unresectable or metastatic disease, are not surgical candidates, or display disease progression despite the addition of neoadjuvant chemoradiotherapy to surgery. Need for improved palliation exits. CASE PRESENTATION: This case describes a 73-year-old African American male who presented with recurrent squamous cell carcinoma (SCCA) of the esophagus who has a achieved complete remission for 24 months via endoscopic cryospray ablation. CONCLUSION: Endoscopic cryo spray ablation warrants further investigation as a palliative treatment modality for esophageal cancer. This is the first reported case in the medical literature

Differences in the bovine milk whey proteome between early pregnancy and the estrous cycle

peer-reviewedCurrent bovine pregnancy detection methods are not reliable until at least day 28 post artificial insemination (AI). The bovine estrous cycle is approximately 21 days; consequently, producers miss an opportunity to rebreed at the next estrous event. Therefore, commercial interest exists for the discovery of novel biomarkers of pregnancy which could reliably detect pregnancy status at or before day 21 of pregnancy. The objective of the present study was to use liquid chromatography tandem mass spectrometry (LC-MS/MS) to perform a global, label-free, proteomics study on (i) milk whey and (ii) extracellular vesicle (EV) enriched milk whey samples, from day 21 of pregnancy, compared with day 21 of the estrous cycle, in order to identify potential protein biomarkers of early pregnancy. The estrous cycles of 10 dairy cows were synchronized, they went through one (control) estrous cycle and these cows were artificially inseminated during the following estrus. These cows were confirmed pregnant by ultrasound scanning. Milk whey samples were collected on day 21 of the estrous cycle and on day 21 post AI. Milk whey samples and EV enriched milk whey samples were analyzed by LC-MS/MS and subsequent analyzes of the label-free quantitative data was performed in MaxQuant and Perseus. Four proteins (APOB, SPADH1, PLIN2 and LPO) were differentially expressed between the proteomes of milk whey from day 21 of pregnancy and day 21 of the estrous cycle (P < 0.05). Ten proteins (PIGR, PGD, QSOX1, MUC1, SRPRA, MD2, GAPDH, FOLR1, GPRC5B and HHIPL2) were differentially expressed between the proteomes of EV enriched milk whey from day 21 of pregnancy and day 21 of the estrous cycle (P < 0.05). These proteins are potential milk whey biomarkers of early pregnancy

The Full-sky Astrometric Mapping Explorer -- Astrometry for the New Millennium

FAME is designed to perform an all-sky, astrometric survey with unprecedented accuracy. It will create a rigid astrometric catalog of 4x10^7 stars with 5 < m_V < 15. For bright stars, 5 < m_V < 9, FAME will determine positions and parallaxes accurate to < 50 microarcseconds, with proper motion errors < 50 microarcseconds/year. For fainter stars, 9 < m_V < 15, FAME will determine positions and parallaxes accurate to < 500 microarcseconds, with proper motion errors < 500 microarcseconds/year. It will also collect photometric data on these 4 x 10^7 stars in four Sloan DSS colors.Comment: 6 pages, 4 figures, to appear in "Working on the Fringe

Subcellular localization of the Arabidopsis thaliana atDjC37 molecular chaperone protein

Abstract only availableThere are 94 genes encoding J-domain molecular chaperone proteins in the Arabidopsis thaliana genome. These genes have been grouped into 51 families (Miernyk 2001 Cell Stress Chaperones 6: 209-218). Family 4 consists of two proteins, atDjC6 and atDjC37. It has been previously determined that atDjC6 is nuclear localized (Suo & Miernyk 2004 Protoplasma 224: 79-89). We now wish to determine the subcellular localization of atDjC37. In silico analysis of the atDjC37 deduced amino acid sequence (http://maple.bioc.columbia.edu/predictNLS/) yielded the prediction that residues -R253RSSKKS- comprise a nuclear localization signal (NLS) sequence. Our experimental strategy has been to construct plasmids that encode full-length atDjC37 protein and a C-terminal truncated version that lacks the NLS sequence, fused to the red fluorescent protein. These proteins will be transiently expressed in biolistically-transformed tobacco BY2 cells, and localized using laser-scanning confocal microscopy. The transformed cells will be simultaneously incubated with a fluorescent nuclear stain to test for signal coincidence. Four nuclear stains are being evaluated for their utility; propidium iodide (PI), DAPI, SYTO Green, and Hoechst 33342. The SYTO and Hoechst 33342 stains are considered cell-permeant, while DAPI is "semi-permeant" and PI is impermeant. The PI and DAPI stains are UV blue-fluorescent, while PI is red and SYTO Green is, naturally, green.Plant Genomics Internship @ M

Picosecond electric-field-induced threshold switching in phase-change materials

Many chalcogenide glasses undergo a breakdown in electronic resistance above a critical field strength. Known as threshold switching, this mechanism enables field-induced crystallization in emerging phase-change memory. Purely electronic as well as crystal nucleation assisted models have been employed to explain the electronic breakdown. Here, picosecond electric pulses are used to excite amorphous Ag$_4$In$_3$Sb$_{67}$Te$_{26}$. Field-dependent reversible changes in conductivity and pulse-driven crystallization are observed. The present results show that threshold switching can take place within the electric pulse on sub-picosecond time-scales - faster than crystals can nucleate. This supports purely electronic models of threshold switching and reveals potential applications as an ultrafast electronic switch.Comment: 6 pages manuscript with 3 figures and 8 pages supplementary materia

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p &#60; 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD

In vivo Bioluminescence Imaging of Burkholderia mallei Respiratory Infection and Treatment in the Mouse Model

Bioluminescent imaging (BLI) technology is a powerful tool for monitoring infectious disease progression and treatment approaches. BLI is particularly useful for tracking fastidious intracellular pathogens that might be difficult to recover from certain organs. Burkholderia mallei, the causative agent of glanders, is a facultative intracellular pathogen and has been classified by the CDC as a Category B select agent due to its highly infectious nature and potential use as a biological weapon. Very little is known regarding pathogenesis or treatment of glanders. We investigated the use of bioluminescent reporter constructs to monitor the dynamics of infection as well as the efficacy of therapeutics for B. mallei in real-time. A stable luminescent reporter B. mallei strain was created using the pUTmini-Tn5::luxKm2 plasmid and used to monitor glanders in the BALB/c murine model. Mice were infected via the intranasal route with 5 × 103 bacteria and monitored by BLI at 24, 48, and 72 h. We verified that our reporter construct maintained similar virulence and growth kinetics compared to wild-type B. mallei and confirmed that it maintains luminescent stability in the presence or absence of antibiotic selection. The luminescent signal was initially seen in the lungs, and progressed to the liver and spleen over the course of infection. We demonstrated that antibiotic treatment 24 h post-infection resulted in reduction of bioluminescence that can be attributed to decreased bacterial burden in target organs. These findings suggest that BLI can be used to monitor disease progression and efficacy of therapeutics during glanders infections. Finally, we report an alternative method to mini-Tn5::luxKm2 transposon using mini-Tn7-lux elements that insert site-specifically at known genomic attachment sites and that can also be used to tag bacteria

Sex-Stratified Genome-Wide Association Study of Multisite Chronic Pain in UK Biobank

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception

Effects of Inherent Tissue Anisotropy on Measurements Obtained with a Clinical Ultrasonic Imaging System

Our overall goal is to develop clinically applicable tissue characterization methods, based on quantitative analyses of backscattered ultrasound, which can differentiate normal from diseased heart segments. In implementing these methods there is a need to compensate for the inherent anisotropic properties of the heart that are exhibited in echocardiographic images. [1–4] Furthermore, quantitative tissue characterization methods may be able to exploit the inherent anisotropy of the myocardium to achieve assessment of cardiac properties.[5–9] The specific aims of this investigation were to measure the spectral properties of backscattered ultrasound using a clinical imaging system and to determine effects of inherent tissue anisotropy on measured spectral properties of backscattered ultrasound