Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Behaviour sequelae following acute Kawasaki disease.

BACKGROUND: Kawasaki disease is a systemic vasculitis and may affect cerebral function acutely. The aim of the present study was to measure a number of behaviour and social parameters within a cohort of Kawasaki disease patients. METHODS: Parents of children with past diagnosis of Kawasaki disease were recruited to complete several behaviour screening questionnaires. Sixty five sets of questionnaires relating to the patient cohort received were eligible for inclusion. Two control groups were used, a hospital (HC) control and a sibling control (SC) group. RESULTS: 40% of the Kawasaki disease group showed elevated internalising scores in the clinical or borderline-clinical range. This compared with 18% of hospital controls and 13% of sibling controls. Additionally, the Kawasaki disease (KD) group were shown to be experiencing greater overall total difficulties when compared with the controls (KD 13.7, HC 8.6, SC 8.9). The KD group attained higher behavioural scores within the internalising sub-categories of somatic problems (KD 61, HC 57, SC 54) and withdrawn traits (KD 56, HC 53, SC 51). The KD group were also shown to be suffering more thought problems (KD 57, HC 53, SC 50) compared with the controls. Further difficulties relating to conduct (KD 3.3, HC 1.4) and social interactions (KD 6.7, HC 8.3) are also highlighted for the KD group compared with hospital controls. Positron emission tomograms were performed on nine patients to investigate severe behavioural problems. Three showed minor changes, possibly a resolving cerebral vasculopathy. CONCLUSION: Kawasaki disease can be associated with significant behavioural sequelae. This is an important consideration in the long-term follow up and referral to a clinical psychologist may be necessary in selected patients

Enhanced recovery program in laparoscopic colectomy for cancer

Introduction: Both laparoscopic colectomy and application of enhanced recovery program (ERP) in open colectomy have been demonstrated to enable early recovery and to shorten hospital stay. This study evaluated the impact of ERP on results of laparoscopic colectomy and comparison was made with the outcomes of patients prior to the application of ERP. Methods: An ERP was implemented in the authors' center in December 2006. Short-term outcomes of consecutive 84 patients who underwent laparoscopic colonic cancer resection 23 months before (control group) and 96 patients who were operated within 13 months; after application of ERP (ERP group) were compared. Results: Between the ERP and control groups, there was no statistical difference in patient characteristics, pathology, operating time, blood loss, conversion rate or complications. Compared to the control group, patients in the ERP group had earlier passage of flatus [2 (range: 1-5) versus 2 (range: 1-4) days after operation respectively; p∈=∈0.03)] and a lower incidence of prolonged post-operative ileus (6% versus 0 respectively; p∈=∈0.02). There was no difference in the hospital stay between the two groups [4 (range: 2-34) days in control group and 4 (range: 2-23) days in ERP group; p∈=∈0.4)]. The re-admission rate was also similar (7% in control group and 5% in ERP group; p∈=∈0.59). Conclusions: In laparoscopic colectomy for cancer, application of ERP was associated with no increase in complication rate but significant improvement of gastrointestinal function. ERP further hastened patient recovery but resulted in no difference in hospital stay. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 31 May 201

A Monte Carlo simulation of the Sudbury Neutrino Observatory proportional counters

The third phase of the Sudbury Neutrino Observatory (SNO) experiment added an array of 3He proportional counters to the detector. The purpose of this Neutral Current Detection (NCD) array was to observe neutrons resulting from neutral-current solar neutrino-deuteron interactions. We have developed a detailed simulation of the current pulses from the NCD array proportional counters, from the primary neutron capture on 3He through the NCD array signal-processing electronics. This NCD array Monte Carlo simulation was used to model the alpha-decay background in SNO's third-phase 8B solar-neutrino measurement.Comment: 38 pages; submitted to the New Journal of Physic

Detection of Mycobacterium ulcerans by the Loop Mediated Isothermal Amplification Method

In order to develop a simple and rapid test that can be used to diagnose Buruli ulcer under field conditions, we modified the conventional LAMP assay by using a disposable pocket warmer as a heating device for generating a constant temperature for the test reaction and employed the use of crude sample preparations consisting of boiled and unboiled extracts of the clinical specimen instead of using purified DNA as the diagnostic specimen. Thirty clinical specimens from suspected Buruli ulcer patients were investigated by the modified LAMP (or pocket warmer LAMP) and the conventional LAMP, as well as IS2404 PCR, a reference method for the detection of Mycobacterium ulcerans. There was no significant difference in the detection rate (63–70%) in all of the methods when purified samples were used for the tests. On the other hand the use of crude specimen preparation resulted in a drop in detection rate (30–40%). This study demonstrates that the LAMP test can be used for rapid detection of M. ulcerans when purified DNA preparations are used. With further improvements in the sample reaction, as well as in specimen purification, the pocket warmer LAMP may provide a simple and rapid diagnostic test for Buruli ulcer

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G2–M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G2–M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposide-induced G2–M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II α levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II α, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies

Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT

Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100 MeV 200 GeV) gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure

Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3

Context. Recently, the high-energy (HE, 0.1-100 GeV) $\gamma$-ray emission from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered to be modulated with a 10.3-day period, making it the first extra-galactic $\gamma$-ray binary. Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV) $\gamma$-ray emission and the search for modulation of the VHE signal with the orbital period of the binary system. Methods. LMC P3 has been observed with the High Energy Stereoscopic System (H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has been folded with the known orbital period of the system in order to test for variability of the emission. Energy spectra are obtained for the orbit-averaged data set, and for the orbital phase bin around the VHE maximum. Results. VHE $\gamma$-ray emission is detected with a statistical significance of 6.4 $\sigma$. The data clearly show variability which is phase-locked to the orbital period of the system. Periodicity cannot be deduced from the H.E.S.S. data set alone. The orbit-averaged luminosity in the $1-10$ TeV energy range is $(1.4 \pm 0.2) \times 10^{35}$ erg/s. A luminosity of $(5 \pm 1) \times 10^{35}$ erg/s is reached during 20% of the orbit. HE and VHE $\gamma$-ray emissions are anti-correlated. LMC P3 is the most luminous $\gamma$-ray binary known so far.Comment: 5 pages, 3 figures, 1 table, accepted for publication in A&

2020 American College of Rheumatology Guideline for the Management of Gout

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/1/art41247.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155484/2/art41247_am.pd

Total Intermittent Pringle Maneuver during Liver Resection Can Induce Intestinal Epithelial Cell Damage and Endotoxemia

Contains fulltext : 110009.pdf (publisher's version ) (Open Access)OBJECTIVES: The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM. METHODS: Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day. RESULTS: 24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed. CONCLUSION: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099475