CX3CR1 Polymorphisms are associated with atopy but not asthma in German children

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden ( n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 ( 95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. Copyright (c) 2007 S. Karger AG, Basel

Hardware in the Loop Testing of an Iodine-Fed Hall Thruster

CUBESATS are relatively new spacecraft platforms that are typically deployed from a launch vehicle as a secondary payload,1 providing low-cost access to space for a wide range of end-users. These satellites are comprised of building blocks having dimensions of 10x10x10 cm cu and a mass of 1.33 kg (a 1-U size). While providing low-cost access to space, a major operational limitation is the lack of a propulsion system that can fit within a CubeSat and is capable of executing high delta v maneuvers. This makes it difficult to use CubeSats on missions requiring certain types of maneuvers (i.e. formation flying, spacecraft rendezvous). Recently, work has been performed investigating the use of iodine as a propellant for Hall-effect thrusters (HETs) 2 that could subsequently be used to provide a high specific impulse path to CubeSat propulsion. Iodine stores as a dense solid at very low pressures, making it acceptable as a propellant on a secondary payload. It has exceptionally high Isp (density times specific impulse), making it an enabling technology for small satellite near-term applications and providing the potential for systems-level advantages over mid-term high power electric propulsion options. Iodine flow can also be thermally regulated, subliming at relatively low temperature ( less than100 C) to yield I2 vapor at or below 50 torr. At low power, the measured performance of an iodine-fed HET is very similar to that of a state-of-the-art xenon-fed thruster. Just as importantly, the current-voltage discharge characteristics of low power iodine-fed and xenon-fed thrusters are remarkably similar, potentially reducing development and qualifications costs by making it possible to use an already-qualified xenon-HET PPU in an iodine-fed system. Finally, a cold surface can be installed in a vacuum test chamber on which expended iodine propellant can deposit. In addition, the temperature doesn't have to be extremely cold to maintain a low vapor pressure in the vacuum chamber (it is under 10(exp -6) torr at -75 C), making it possible to 'cryopump' the propellant with lower-cost recirculating refrigerant-based systems as opposed to using liquid nitrogen or low temperature gaseous helium cryopanels. In the present paper, we describe testing performed using an iodine-fed 200 W Hall thruster mounted to a thrust stand and operated in conjunction with MSFCs Small Projects Rapid Integration and Test Environment (SPRITE) Portable Hardware In the Loop (PHIL) hardware. This work is performed in support of the iodine satellite (iSAT) project, which aims to fly a 200-W iodine-fed thruster on a 12-U CubeSat. The SPRITE PHIL hardware allows a given vehicle to do a checkout of its avionics algorithm by allowing it to monitor and feed data to simulated sensors and effectors in a digital environment. These data are then used to determine the attitude of the vehicle and a separate computer is used to interpret the data set and visualize it using a 3D graphical interface. The PHIL hardware allows the testing of the vehicles bus by providing 'real' hardware interfaces (in the case of this test a real RS422 bus) and specific components can be modeled to show their interactions with the avionics algorithm (e.g. a thruster model). For the iSAT project the PHIL is used to visualize the operating cycle of the thruster and the subsequent effect this thrusting has on the attitude of the satellite over a given period of time. The test is controlled using software running on an Andrews Space Cortex 160 flight computer. This computer is the current baseline for a full iSAT mission. While the test could be conducted with a lab computer and software, the team chose to exercise the propulsion system with a representative CubeSat-class computer. For purposes of this test, the "flight" software monitored the propulsion and PPU systems, controlled operation of the thruster, and provided thruster state data to the PHIL simulation. Commands to operate the thruster were initiated from an operator's workstation outside the vacuum chamber and passed through the Cortex 160 to exercise portions of the flight avionics. Two custom-designed pieces of electronics hardware have been designed to operate the propellant feed system. One piece of hardware is an auxiliary board that controls a latch valve, proportional flow control valves (PFCVs) and valve heaters as well as measuring pressures, temperatures and PFCV feedback voltage. An onboard FPGA provides a serial link for issuing commands and manages all lower level input-output functions. The other piece of hardware is a power distribution board, which accepts a standard bus voltage input and converts this voltage into all the different current-voltage types required to operate the auxiliary board. These electronics boards are located in the vacuum chamber near the thruster, exposing this hardware to both the vacuum and plasma environments they would encounter during a mission, with these components communicating to the flight computer through an RS-422 interface. The auxiliary board FPGA provides a 28V MOSFET switch circuit with a 20ms pulse to open or close the iodine propellant feed system latch valve. The FPGA provides a pulse width modulation (PWM) signal to a DC/DC boost converter to produce the 12-120V needed for control of the proportional flow control valve. There are eight MOSFET-switched heating circuits in the system. Heaters are 28V and located in the latch valve, PFCV, propellant tank and propellant feed lines. Both the latch valve and PFCV have thermistors built into them for temperature monitoring. There are also seven resistance temperature device (RTD) circuits on the auxiliary board that can be used to measure the propellant tank and feedline temperatures. The signals are conditioned and sent to an analog to digital converter (ADC), which is directly commanded and controlled by the FPGA

S.13.1 Safety and efficacy of rituximab in SSc: an analysis from the European Scleroderma Trial and Research Group

Objectives. Objective of this multicentre, observational study was to assess effects and safety of rituximab (RTX) using the European Scleroderma Trial and Research Group (EUSTAR) cohort. Methods. EUSTAR centres were asked to provide specific data about SSc patients treated with RTX. Primary endpoints were predefined for different disease manifestations and compared between baseline and follow-up. Normally distributed data, analysed by paired t-test, are shown as mean (s.d.), and non-parametric data, analysed by Wilcoxon matched paired signed-rank test, are shown as median and interquartile range. Results. Data on 72 SSc patients treated with RTX were captured from 27 EUSTAR centres (51 females/21 males, 52 diffuse/19 limited, age 51 (44-60) years, disease duration 6 (3-10) years, 47 anti-Scl-70 positive). The most frequent RTX application scheme was 1000 mg × 2 within 2 weeks (57/72 patients). Co-treatment with other immunosuppressive drugs was reported in 28 patients. The modified Rodnan skin score (mRSS) significantly decreased vs baseline at 7 (5-9) months follow-up (n = 47, 18.2 + 10.9 vs 14.5 + 9.9, P = 0.0002). This was true for both patients with later disease stages and also for patients with earlier, extended skin fibrosis (dSSc with mRSS >16 at baseline, n = 26; 26.5 + 6.8 vs 20.4 + 8.9, P < 0.0001, reduction by 29.9%). S-HAQ was unchanged, but the European SSc activity score improved after rituximab treatment [n = 10; 3.7 (2.6-6.4) vs 1.7 (0.9-2.5), P = 0.01]. RTX had no effects on lung fibrosis (FVC, DLCO, TLC, HRCT score) in n = 11 patients with evidence for SSc-ILD. In SSc-polyarthritis patients, the DAS-28 declined at 6 months follow-up without reaching statistical significance [n = 8; 4.8 (2.5-7.5) vs 3.7 (2.6-6.6); p = 0.3]. Of 8, 5patients were RF and/or anti-CCP antibody positive. Similar results were obtained for secondary outcome measures (tender and swollen joint count, VAS, CRP, ESR). Additional positive effects of RTX were seen on SSc-related myopathy (CK levels, 273 + 177 vs 184 + 139; n = 12, P = 0.03) and on digital ulcers [total number per patient 1 (1-3) vs 0 (0-1); n = 23; P = 0.0086]. During RTX treatment 14 patients had infections, 3 serum sickness, 2 allergic reactions and 1 lung fibrosis aggravation, 29 fatigue and 9 nausea. Four patients died, one possibly related to RTX treatment (pneumonia and cardiac failure 1.5 months after RTX infusion). Conclusion. This large EUSTAR cohort study points at positive effects of RTX in particular on skin fibrosis, and suggests randomized controlled trial in SSc patient

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases

Unicentric or multicentric castleman disease? A case report of a pelvic intraperitoneal mass in a middle aged woman

Castleman Disease is a lymphoid disorder characterized by the presence of an enlarged or abnormal lymph node/lymphatic tissue. The disease is classified into unicentric or multicentric variants. The unicentric form is a benign disorder that is usually asymptomatic and consists of a single lymphoid mass that is predominantly located in the mediastinum, but can also rarely develop in the neck or abdomen. The multicentric type involves more than one lymphatic station and is related to the presence of type B symptoms (fevers, night sweats and weight loss), HIV/HHV8 infection and increased serum IL-6 levels. We present the case of an unusual pelvic intraperitoneal manifestation of Castleman Disease in a 52-year-old caucasian woman who showed clinical, radiological, histological and laboratory findings common to both Unicentric and Multicentric Castleman Disease

Perilous state of critically endangered Northwest African cheetah (Acinonyx jubatus hecki) across the Sudano-Sahel

Northwest African cheetah populations have declined precipitously, with expert opinion estimating that <420 individuals persist across parts of Algeria, Benin, Burkina Faso, Chad, Niger and Mali. However, no reliable density estimates exist in the remaining subspecies strongholds throughout the Sudano-Sahel Zone, including the W-Arly-Pendjari Complex and Greater Zakouma Ecosystem within the Bahr/Salamat landscape. Camera trap surveys were combined with spatially explicit capture–recapture methodologies in both regions to estimate the cheetah density and detectable demographic composition of these populations. Following 15 429 camera trap nights, we detected nine individuals during the dry season and four individuals during the wet season in Pendjari (2021), nine individuals (dry season; 2023) in Zakouma and none in Siniaka Minia. Cheetah densities were thus estimated at 0.17–0.24 and 0.37 cheetah per 100 km2 in Pendjari and Zakouma, respectively. While marginally higher than predicted, such low-density estimates are concerning in the last remaining habitats harbouring this critically endangered subspecies. Considering the substantial contraction of regional cheetah distribution, we estimate an overall population size of 68 ± 29 individuals across the studied areas. These novel estimates are among the lowest formally determined densities throughout cheetah range in Africa, where a high frequency of people and livestock detected on camera traps highlight the ongoing risks to large carnivores in these protected areas. Subsequent management recommendations include implementation of the established regional conservation strategies that encompass the distributional range of these cheetah, continuous monitoring of populations, genetic analyses to inform management, curbing illegal trade and increasing international awareness around the plight of the subspecies

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Neurotransmitter receptor trafficking during synaptic plasticity requires the concerted action of multiple signaling pathways and the protein transport machinery. However, little is known about the contribution of lipid metabolism during these processes. In this paper, we addressed the question of the role of cholesterol in synaptic changes during long-term potentiation (LTP). We found that N-methyl-d-aspartate-type glutamate receptor (NMDAR) activation during LTP induction leads to a rapid and sustained loss or redistribution of intracellular cholesterol in the neuron. A reduction in cholesterol, in turn, leads to the activation of Cdc42 and the mobilization of GluA1-containing α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) from Rab11-recycling endosomes into the synaptic membrane, leading to synaptic potentiation. This process is accompanied by an increase of NMDAR function and an enhancement of LTP. These results imply that cholesterol acts as a sensor of NMDAR activation and as a trigger of downstream signaling to engage small GTPase (guanosine triphosphatase) activation and AMPAR synaptic delivery during LTP.Peer Reviewe

Feasibility of short term drainage for diagnostic thoracoscopy

Background and Aim. Thoracoscopy is a diagnostic tool superior to other available techniques for the assessment of pleural effusions. There are numerous publications that describe the technique in detail but there is very little published on the optimal time of chest drain removal post procedure. Our aim was to retrospectively study all cases of diagnostic thoracoscopy and to ascertain the time of chest drain removal, length of hospital stay and associated complications. Methods. All patients who underwent thoracoscopy during a 6-year period were identified from a computerised database. Patients who received talc for pleurodesis were excluded as they required longer drainage time. A review of the remaining patients’ charts and radiology was performed to ascertain the predefined outcomes. Results. 124 patients had a diagnostic thoracoscopy. The time to chest drain removal was documented as less than four hours, four to 24 hours, 24 to 48 hours and greater than 48 hours in 66 (53.2%), 29 (23.4%), 12 (9.7%) and 17 (13.7%) of patients respectively. The median length of stay for all patients was one day (interquartile range, 1-4 days). There was a statistically significant difference in overall length of hospital stay between the early (48 hours) chest drain removal groups, p=0.0028. The overall complication rate was 15.9%. There was no statistical difference in complication rates between the two groups. Conclusion. This retrospective series demonstrates that early chest drain removal post diagnostic thoracoscopy is possible and safe. This is likely to confer economic benefits

The formin INF2 regulates basolateral-to-apical transcytosis and lumen formation in association with Cdc42 and MAL2

Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation. © 2010 Elsevier Inc.This work was supported by grants (BFU2006-01925, BFU2009-07886, and CONSOLIDER COAT CSD2009-00016) to M.A.A. from the Ministerio de Ciencia e Innovación (MICINN), Spain. R.M. is the holder of a contract from the Ramón y Cajal Program of the MICINN. The authors declare no competing financial interests