Simultaneous islet-kidney vs pancreas-kidney transplantation in type 1 diabetes mellitus: a 5year single centre follow-up

Aims/hypothesis: The aim of this study was to compare the long-term outcomes—in terms of glucose control, renal function and procedure-related complications—of simultaneous islet-kidney (SIK) transplantation with those of simultaneous pancreas-kidney (SPK) transplantation in patients with type 1 diabetes mellitus. Methods: HbA1c, need for insulin, GFR and complication rate were compared between 13 recipients of SIK and 25 recipients of SPK transplants at the same institution. The mean follow-up was 41months. Results: Two primary organ non-functions occurred in the SIK group. HbA1c did not differ at any time point during follow-up in the SIK group compared with the SPK group (mean during follow-up 6.3 vs 5.9%). Similarly, kidney function over time was not different between the two groups. A higher rate of insulin independence following SPK transplantation (after 1year 96 vs 31% in the SIK group) was counterbalanced by a higher rate of serious adverse events (40% relaparotomies vs 0% in the SIK group). Conclusions/interpretation: The endogenous insulin production achieved by islet transplantation, combined with optimal insulin therapy, was sufficient for maintaining near-normal glucose levels. In terms of glucose control, islet transplantation provides results comparable to those achieved with pancreas transplantation. However, SPK results in a higher rate of insulin independence, albeit at the cost of more surgical complications. These results have led to a new paradigm in islet transplantation at our institution, where the primary goal is not insulin independence, but good glucose control and avoidance of severe hypoglycaemi

Pauli's Principle in Probe Microscopy

Exceptionally clear images of intramolecular structure can be attained in dynamic force microscopy through the combination of a passivated tip apex and operation in what has become known as the "Pauli exclusion regime" of the tip-sample interaction. We discuss, from an experimentalist's perspective, a number of aspects of the exclusion principle which underpin this ability to achieve submolecular resolution. Our particular focus is on the origins, history, and interpretation of Pauli's principle in the context of interatomic and intermolecular interactions.Comment: This is a chapter from "Imaging and Manipulation of Adsorbates using Dynamic Force Microscopy", a book which is part of the "Advances in Atom and Single Molecule Machines" series published by Springer [http://www.springer.com/series/10425]. To be published late 201

Operational experience, improvements, and performance of the CDF Run II silicon vertex detector

The Collider Detector at Fermilab (CDF) pursues a broad physics program at Fermilab's Tevatron collider. Between Run II commissioning in early 2001 and the end of operations in September 2011, the Tevatron delivered 12 fb-1 of integrated luminosity of p-pbar collisions at sqrt(s)=1.96 TeV. Many physics analyses undertaken by CDF require heavy flavor tagging with large charged particle tracking acceptance. To realize these goals, in 2001 CDF installed eight layers of silicon microstrip detectors around its interaction region. These detectors were designed for 2--5 years of operation, radiation doses up to 2 Mrad (0.02 Gy), and were expected to be replaced in 2004. The sensors were not replaced, and the Tevatron run was extended for several years beyond its design, exposing the sensors and electronics to much higher radiation doses than anticipated. In this paper we describe the operational challenges encountered over the past 10 years of running the CDF silicon detectors, the preventive measures undertaken, and the improvements made along the way to ensure their optimal performance for collecting high quality physics data. In addition, we describe the quantities and methods used to monitor radiation damage in the sensors for optimal performance and summarize the detector performance quantities important to CDF's physics program, including vertex resolution, heavy flavor tagging, and silicon vertex trigger performance.Comment: Preprint accepted for publication in Nuclear Instruments and Methods A (07/31/2013

Bacterial Distribution in the Rhizosphere of Wild Barley under Contrasting Microclimates

Background: All plants in nature harbor a diverse community of rhizosphere bacteria which can affect the plant growth. Our samples are isolated from the rhizosphere of wild barley Hordeum spontaneum at the Evolution Canyon (‘EC’), Israel. The bacteria which have been living in close relationship with the plant root under the stressful conditions over millennia are likely to have developed strategies to alleviate plant stress. Methodology/Principal Findings: We studied distribution of culturable bacteria in the rhizosphere of H. spontaneum and characterized the bacterial 1-aminocyclopropane-1-carboxylate deaminase (ACCd) production, biofilm production, phosphorus solubilization and halophilic behavior. We have shown that the H. spontaneum rhizosphere at the stressful South Facing Slope (SFS) harbors significantly higher population of ACCd producing biofilm forming phosphorus solubilizing osmotic stress tolerant bacteria. Conclusions/Significance: The long-lived natural laboratory ‘EC ’ facilitates the generation of theoretical testable and predictable models of biodiversity and genome evolution on the area of plant microbe interactions. It is likely that the bacteria isolated at the stressful SFS offer new opportunities for the biotechnological applications in our agro-ecologica

Fermilab Main Injector Beam Position Monitor Upgrade

An upgrade of the Beam Position Monitor (BPM) signal processing and data acquisition system for the Fermilab Main Injector is described. The Main Injector is a fast cycling synchrotron that accelerates protons or antiprotons from 8 to 150 GeV. Each Main Injector cycle can have a totally different magnet ramp, RF frequency configuration, beam bunch structure, and injection/extraction pattern from the previous cycle. The new BPM system provides the capabilities and flexibility required by the dynamic and complex machine operations. The system offers measurement capability in the 2.5 MHz and 53 MHz channels to detect the range of bunch structures for protons and antiprotons in both wideband (turn-by-turn) and narrowband (closed-orbit) modes. The new BPM read-out system is based on the digital receiver concept and is highly configurable, allowing the signal processing of nearly all Main Injector beam conditions, including the detection of individual batches. An overview of the BPM system in the Main Injector operating environment, some technology details and first beam measurements are presented

SSR and AFLP based genetic diversity of soybean germplasm differing in photoperiod sensitivity

Forty-four soybean genotypes with different photoperiod response were selected after screening of 1000 soybean accessions under artificial condition and were profiled using 40 SSR and 5 AFLP primer pairs. The average polymorphism information content (PIC) for SSR and AFLP marker systems was 0.507 and 0.120, respectively. Clustering of genotypes was done using UPGMA method for SSR and AFLP and correlation was 0.337 and 0.504, respectively. Mantel's correlation coefficients between Jaccard's similarity coefficient and the cophenetic values were fairly high in both the marker systems (SSR = 0.924; AFLP = 0.958) indicating very good fit for the clustering pattern. UPGMA based cluster analysis classified soybean genotypes into four major groups with fairly moderate bootstrap support. These major clusters corresponded with the photoperiod response and place of origin. The results indicate that the photoperiod insensitive genotypes, 11/2/1939 (EC 325097) and MACS 330 would be better choice for broadening the genetic base of soybean for this trait

Evolutionary Diversification of SPANX-N Sperm Protein Gene Structure and Expression

The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage ∼7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well

Phase Coupling of a Circadian Neuropeptide With Rest/Activity Rhythms Detected Using a Membrane-Tethered Spider Toxin

Drosophila clock neurons are self-sustaining cellular oscillators that rely on negative transcriptional feedback to keep circadian time. Proper regulation of organismal rhythms of physiology and behavior requires coordination of the oscillations of individual clock neurons within the circadian control network. Over the last decade, it has become clear that a key mechanism for intercellular communication in the circadian network is signaling between a subset of clock neurons that secrete the neuropeptide pigment dispersing factor (PDF) and clock neurons that possess its G protein-coupled receptor (PDFR). Furthermore, the specific hypothesis has been proposed that PDF-secreting clock neurons entrain the phase of organismal rhythms, and the cellular oscillations of other clock neurons, via the temporal patterning of secreted PDF signals. In order to test this hypothesis, we have devised a novel technique for altering the phase relationship between circadian transcriptional feedback oscillation and PDF secretion by using an ion channel–directed spider toxin to modify voltage-gated Na+ channel inactivation in vivo. This technique relies on the previously reported “tethered-toxin” technology for cell-autonomous modulation of ionic conductances via heterologous expression of subtype-specific peptide ion channel toxins as chimeric fusion proteins tethered to the plasma membrane with a glycosylphosphatidylinositol (GPI) anchor. We demonstrate for the first time, to our knowledge, the utility of the tethered-toxin technology in a transgenic animal, validating four different tethered spider toxin ion channel modifiers for use in Drosophila. Focusing on one of these toxins, we show that GPI-tethered Australian funnel-web spider toxin δ-ACTX-Hv1a inhibits Drosophila para voltage-gated Na+ channel inactivation when coexpressed in Xenopus oocytes. Transgenic expression of membrane-tethered δ-ACTX-Hv1a in vivo in the PDF-secreting subset of clock neurons induces rhythmic action potential bursts and depolarized plateau potentials. These in vitro and in vivo electrophysiological effects of membrane-tethered δ-ACTX-Hv1a are consistent with the effects of soluble δ-ACTX-Hv1a purified from venom on Na+ channel physiological and biophysical properties in cockroach neurons. Membrane-tethered δ-ACTX-Hv1a expression in the PDF-secreting subset of clock neurons induces an approximately 4-h phase advance of the rhythm of PDF accumulation in their terminals relative to both the phase of the day:night cycle and the phase of the circadian transcriptional feedback loops. As a consequence, the morning anticipatory peak of locomotor activity preceding dawn, which has been shown to be driven by the clocks of the PDF-secreting subset of clock neurons, phase advances coordinately with the phase of the PDF rhythm of the PDF-secreting clock neurons, rather than maintaining its phase relationship with the day:night cycle and circadian transcriptional feedback loops. These results (1) validate the tethered-toxin technology for cell-autonomous modulation of ion channel biophysical properties in vivo in transgenic Drosophila, (2) demonstrate that the kinetics of para Na+ channel inactivation is a key parameter for determining the phase relationship between circadian transcriptional feedback oscillation and PDF secretion, and (3) provide experimental support for the hypothesis that PDF-secreting clock neurons entrain the phase of organismal rhythms via the temporal patterning of secreted PDF signals

A systematic evaluation of expression of HERV-W elements; influence of genomic context, viral structure and orientation

<p>Abstract</p> <p>Background</p> <p>One member of the W family of human endogenous retroviruses (HERV) appears to have been functionally adopted by the human host. Nevertheless, a highly diversified and regulated transcription from a range of HERV-W elements has been observed in human tissues and cells. Aberrant expression of members of this family has also been associated with human disease such as multiple sclerosis (MS) and schizophrenia. It is not known whether this broad expression of HERV-W elements represents transcriptional leakage or specific transcription initiated from the retroviral promoter in the long terminal repeat (LTR) region. Therefore, potential influences of genomic context, structure and orientation on the expression levels of individual HERV-W elements in normal human tissues were systematically investigated.</p> <p>Results</p> <p>Whereas intronic HERV-W elements with a pseudogene structure exhibited a strong anti-sense orientation bias, intronic elements with a proviral structure and solo LTRs did not. Although a highly variable expression across tissues and elements was observed, systematic effects of context, structure and orientation were also observed. Elements located in intronic regions appeared to be expressed at higher levels than elements located in intergenic regions. Intronic elements with proviral structures were expressed at higher levels than those elements bearing hallmarks of processed pseudogenes or solo LTRs. Relative to their corresponding genes, intronic elements integrated on the sense strand appeared to be transcribed at higher levels than those integrated on the anti-sense strand. Moreover, the expression of proviral elements appeared to be independent from that of their corresponding genes.</p> <p>Conclusions</p> <p>Intronic HERV-W provirus integrations on the sense strand appear to have elicited a weaker negative selection than pseudogene integrations of transcripts from such elements. Our current findings suggest that the previously observed diversified and tissue-specific expression of elements in the HERV-W family is the result of both directed transcription (involving both the LTR and internal sequence) and leaky transcription of HERV-W elements in normal human tissues.</p