Foetal haemoglobin-blood cells (F-cells) as a feature of embryonic tumours (blastomas)

Tumour markers are important in the diagnosis and monitoring of many tumours. This study tested the hypothesis that an oncofoetal protein, foetal haemoglobin (HbF) is a potential tumour marker in embryonic tumours, useful for management. An immunohistochemical investigation of HbF blood cell (Fc) distribution was carried out in tumours and in bone marrow samples from 83 children and 13 adults with various embryonic tumours (blastomas), and in bone marrow samples of 24 leukaemia patients. In the three, main blastoma types, nephroblastoma (Wilms' tumour), neuroblastoma and retinoblastoma, where all the patients, except two, were children, around 80% of the tumour samples had Fc within proliferating blood vessels and spaces between tumour cells. In parallel, clusters of Fc, mostly F-erythroblasts (Feb), were distributed in the bone marrow of some of those patients and in the bone marrow of 79% of the leukaemia patients. Foetal haemoglobin, as well as being a potential prognostic cancer marker, is a potential indicator of DNA hypomethylation implicated in the development of these tumours, as well as in others previously noted for the presence of HbF

Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data

Abstract Objective To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens. Methods Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data. Results The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences. Conclusion Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients

Sulforaphane-enriched extracts from glucoraphanin-rich broccoli exert antimicrobial activity against gut pathogens in vitro and innovative cooking methods increase in vivo intestinal delivery of sulforaphane

Purpose Studies on broccoli (Brassica oleracea var. italica) indicate beneficial effects against a range of chronic diseases, commonly attributed to their bioactive phytochemicals. Sulforaphane, the bioactive form of glucoraphanin, is formed by the action of the indigenous enzyme myrosinase. This study explored the role that digestion and cooking practices play in bioactivity and bioavailability, especially the rarely considered dose delivered to the colon. Methods The antimicrobial activity of sulforaphane extracts from raw, cooked super broccoli and cooked super broccoli plus mustard seeds (as a source myrosinase) was assessed. The persistence of broccoli phytochemicals in the upper gastrointestinal tract was analysed in the ileal fluid of 11 ileostomates fed, in a cross-over design, super broccoli soup prepared with and without mustard seeds. Results The raw super broccoli had no antimicrobial activity, except against Bacillus cereus, but cooked super broccoli (with and without mustard seeds) showed considerable antimicrobial activity against various tested pathogens. The recovery of sulforaphane in ileal fluids post soup consumption was < 1% but addition of mustard seeds increased colon-available sulforaphane 6-fold. However, when sulforaphane was extracted from the ileal fluid with the highest sulforaphane content and tested against Escherichia coli K12, no inhibitory effects were observed. Analysis of glucosinolates composition in ileal fluids revealed noticeable inter-individual differences, with six “responding” participants showing increases in glucosinolates after broccoli soup consumption. Conclusions Sulforaphane-rich broccoli extracts caused potent antimicrobial effects in vitro, and the consumption of sulforaphane-enriched broccoli soup may inhibit bacterial growth in the stomach and upper small intestine, but not in the terminal ileum or the colon

Tyrosine kinase chromosomal translocations mediate distinct and overlapping gene regulation events

<p>Abstract</p> <p>Background</p> <p>Leukemia is a heterogeneous disease commonly associated with recurrent chromosomal translocations that involve tyrosine kinases including BCR-ABL, TEL-PDGFRB and TEL-JAK2. Most studies on the activated tyrosine kinases have focused on proximal signaling events, but little is known about gene transcription regulated by these fusions.</p> <p>Methods</p> <p>Oligonucleotide microarray was performed to compare mRNA changes attributable to BCR-ABL, TEL-PDGFRB and TEL-JAK2 after 1 week of activation of each fusion in Ba/F3 cell lines. Imatinib was used to control the activation of BCR-ABL and TEL-PDGFRB, and TEL-JAK2-mediated gene expression was examined 1 week after Ba/F3-TEL-JAK2 cells were switched to factor-independent conditions.</p> <p>Results</p> <p>Microarray analysis revealed between 800 to 2000 genes induced or suppressed by two-fold or greater by each tyrosine kinase, with a subset of these genes commonly induced or suppressed among the three fusions. Validation by Quantitative PCR confirmed that eight genes (Dok2, Mrvi1, Isg20, Id1, gp49b, Cxcl10, Scinderin, and collagen Vα1(Col5a1)) displayed an overlapping regulation among the three tested fusion proteins. Stat1 and Gbp1 were induced uniquely by TEL-PDGFRB.</p> <p>Conclusions</p> <p>Our results suggest that BCR-ABL, TEL-PDGFRB and TEL-JAK2 regulate distinct and overlapping gene transcription profiles. Many of the genes identified are known to be involved in processes associated with leukemogenesis, including cell migration, proliferation and differentiation. This study offers the basis for further work that could lead to an understanding of the specificity of diseases caused by these three chromosomal translocations.</p

Song Practice Promotes Acute Vocal Variability at a Key Stage of Sensorimotor Learning

BACKGROUND: Trial by trial variability during motor learning is a feature encoded by the basal ganglia of both humans and songbirds, and is important for reinforcement of optimal motor patterns, including those that produce speech and birdsong. Given the many parallels between these behaviors, songbirds provide a useful model to investigate neural mechanisms underlying vocal learning. In juvenile and adult male zebra finches, endogenous levels of FoxP2, a molecule critical for language, decrease two hours after morning song onset within area X, part of the basal ganglia-forebrain pathway dedicated to song. In juveniles, experimental 'knockdown' of area X FoxP2 results in abnormally variable song in adulthood. These findings motivated our hypothesis that low FoxP2 levels increase vocal variability, enabling vocal motor exploration in normal birds. METHODOLOGY/PRINCIPAL FINDINGS: After two hours in either singing or non-singing conditions (previously shown to produce differential area X FoxP2 levels), phonological and sequential features of the subsequent songs were compared across conditions in the same bird. In line with our prediction, analysis of songs sung by 75 day (75d) birds revealed that syllable structure was more variable and sequence stereotypy was reduced following two hours of continuous practice compared to these features following two hours of non-singing. Similar trends in song were observed in these birds at 65d, despite higher overall within-condition variability at this age. CONCLUSIONS/SIGNIFICANCE: Together with previous work, these findings point to the importance of behaviorally-driven acute periods during song learning that allow for both refinement and reinforcement of motor patterns. Future work is aimed at testing the observation that not only does vocal practice influence expression of molecular networks, but that these networks then influence subsequent variability in these skills

Vocal Learning and Auditory-Vocal Feedback

Vocal learning is usually studied in songbirds and humans, species that can form auditory templates by listening to acoustic models and then learn to vocalize to match the template. Most other species are thought to develop vocalizations without auditory feedback. However, auditory input influences the acoustic structure of vocalizations in a broad distribution of birds and mammals. Vocalizations are dened here as sounds generated by forcing air past vibrating membranes. A vocal motor program may generate vocalizations such as crying or laughter, but auditory feedback may be required for matching precise acoustic features of vocalizations. This chapter discriminates limited vocal learning, which uses auditory input to fine-tune acoustic features of an inherited auditory template, from complex vocal learning, in which novel sounds are learned by matching a learned auditory template. Two or three songbird taxa and four or ve mammalian taxa are known for complex vocal learning. A broader range of mammals converge in the acoustic structure of vocalizations when in socially interacting groups, which qualifies as limited vocal learning. All birds and mammals tested use auditory-vocal feedback to adjust their vocalizations to compensate for the effects of noise, and many species modulate their signals as the costs and benefits of communicating vary. This chapter asks whether some auditory-vocal feedback may have provided neural substrates for the evolution of vocal learning. Progress will require more precise definitions of different forms of vocal learning, broad comparative review of their presence and absence, and behavioral and neurobiological investigations into the mechanisms underlying the skills.PostprintPeer reviewe

IceCube-Gen2: A Vision for the Future of Neutrino Astronomy in Antarctica

20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)20 pages, 12 figures. Address correspondence to: E. Blaufuss, F. Halzen, C. Kopper (Changed to add one missing author, no other changes from initial version.)The recent observation by the IceCube neutrino observatory of an astrophysical flux of neutrinos represents the "first light" in the nascent field of neutrino astronomy. The observed diffuse neutrino flux seems to suggest a much larger level of hadronic activity in the non-thermal universe than previously thought and suggests a rich discovery potential for a larger neutrino observatory. This document presents a vision for an substantial expansion of the current IceCube detector, IceCube-Gen2, including the aim of instrumenting a $10\,\mathrm{km}^3$ volume of clear glacial ice at the South Pole to deliver substantial increases in the astrophysical neutrino sample for all flavors. A detector of this size would have a rich physics program with the goal to resolve the sources of these astrophysical neutrinos, discover GZK neutrinos, and be a leading observatory in future multi-messenger astronomy programs