Seasonal variation of carbon monoxide in northern Japan: Fourier transform IR measurements and source-labeled model calculations

Tropospheric carbon monoxide (CO) was measured throughout 2001 using groundbased Fourier transform IR (FTIR) spectrometers at Moshiri 44.4N and Rikubetsu 43.5N) observatories in northern Japan, which are separated by 150 km. Seasonal and day-to-day variations of CO are studied using these data, and contributions from various CO sources are evaluated using three-dimensional global chemistry transport model (GEOS-CHEM) calculations. Seasonal maximum and minimum FTIR-derived tropospheric CO amounts occurred in April and September, respectively. The ratio of partial column amounts between the 0–4 and 0–12 km altitude ranges is found to be slightly greater in early spring. The GEOS-CHEM model calculations generally reproduce these observed features. Source-labeled CO model calculations suggest that the observed seasonal variation is caused by seasonal contributions from various sources, in addition to a seasonal change in chemical CO loss by OH. Changes in meteorological fields largely control the relative importance of various source contributions. The contributions from fossil fuel (FF) combustion in Asia and photochemical CO production have the greatest yearly averaged contribution at 1 km among the CO sources (31% each). The Asian FF contribution increases from winter to summer, because weak southwesterly wind in summer brings more Asian pollutants to the observation sites. The seasonal variation from photochemical CO production is small (±17% at 1 km), likely because of concurrent increases (decreases) of photochemical production and loss rates in summer (winter), with the largest contribution between August and December. The contribution from intercontinental transport of European FF combustion CO is found to be comparable to that of Asian FF sources in winter. Northwesterly wind around the Siberian high in this season brings pollutants from Europe directly to Japan, in addition to southward transport of accumulated pollution from higher latitudes. The influences are generally greater at lower altitudes, resulting in a vertical gradient in the CO profile during winter. The model underestimates total CO by 12–14% between March and June. Satellite-derived fire-count data and the relationship between FTIR-derived HCN and CO amounts are generally consistent with biomass burning influences, which could have been underestimated by the model calculations

Severe eosinophilic colitis caused by neuropathic agents in a patient with chronic fatigue syndrome and functional abdominal pain: case report and review of the literature

Eosinophilic colitis is a rare clinical condition that belongs to the group of eosinophilic gastrointestinal disorders. Its occurrence can be primary or secondary to infection, medications, or autoimmune/hematological conditions. We present a case of a young female adult with severe chronic fatigue syndrome, widespread chronic pain, including functional abdominal pain, who developed severe eosinophilic colitis following successive treatments with gabapentin and pregabalin. On both occasions, symptoms manifested as abdominal pain, diarrhea, and eosinophilia and improved upon discontinuation of the medications. Magnetic resonance imaging of the small bowel demonstrated an ascending colon colitis, and endoscopic investigations confirmed florid colitis mainly in the ascending colon with biopsies demonstrating a dense eosinophilic infiltrate with micro-abscesses. Serum eosinophil counts correlated well with the timing of the agents’ administration. There was no other organ involvement. Symptoms improved upon discontinuation of the drugs and steroid administration. Eosinophilic colitis is an exceptionally rare entity and its mechanism of action is still unclear. Suspicion of eosinophilic colitis should be raised if a patient presents with abdominal pain, diarrhea, and peripheral eosinophilia following treatment with pregabalin or gabapentin. / Die eosinophile Kolitis ist eine sehr seltene Krankheit aus der Gruppe der eosinophilen Magen-Darm-Erkrankungen. Als Auslöser gelten Primär- und Sekundärinfektionen, Medikamente, sowie autoimmune und hämatologische Erkrankungen. Unser Fall beschreibt eine junge, weibliche Erwachsene mit schwerem chronischem Müdigkeitssyndrom und generalisierten chronischen Schmerzen, darunter funktionellen Unterleibsschmerzen, welche unter Behandlung mit Gabapentin und Pregabalin an einer schweren eosinophilen Kolitis erkrankte. Zu zwei unterschiedlichen Zeitpunkten wies die Patientin abdominelle Schmerzen, Diarrhoe und ein Eosinophilie auf, mit jeweils Verbesserung der Symptomatik nach Sistieren der Medikamenteneinnahme. In einer Kernspintomografie stellte sich eine Kolitis des aufsteigenden Kolons dar. Endoskopisch konnte eine floride Kolitis, vorwiegend im Kolon ascendens, bestätigt werden, mit Nachweis einer dichten eosinophilen Infiltration mit Mikroabszessen in den Biopsien. Die serologische Eosinophilie korrelierte zeitlich mit der Medikamenteneinnahme. Andere Organe waren nicht beteiligt. Die Symptomatik verbesserte sich nach Absetzen der Medikamente und Verabreichung von Steroiden. Die eosinophile Kolitis ist eine ausgesprochen seltene Erkrankung mit bisher noch unklarem Wirkmechanismus. Bei Patienten mit abdominellen Schmerzen, Diarrhoe und peripherer Eosinophilie unter einer Therapie mit Pregabalin oder Gabapentin sollte der Verdacht auf eine eosinophile Kolitis gestellt werden

A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome

Background: Cornelia de Lange syndrome (CdLS) is a rare and clinically variable syndrome characterized by growth impairment, multi-organ anomalies, and a typical set of facial dysmorphisms. Here we describe a 2-year-old female child harboring a novel de novo missense variant in HDAC8, whose phenotypical score, according to the recent consensus on CdLS clinical diagnostic criteria, allowed the diagnosis of a non-classic CdLS. Methods: Clinical exome sequencing was performed on the trio, identifying a de novo heterozygous variant in HDAC8 (NM_018486; c. 356C>G p.Thr119Arg). Molecular modeling was performed to evaluate putative functional consequence of the HDAC8 protein. Results: The variant HDAC8 c.356C>G is classified as pathogenic following the ACMG (American College of Medical Genetics and Genomics)/AMP (Association for Molecular Pathology) guidelines. By molecular modeling, we confirmed the deleterious effect of this variant, since the amino acid change compromises the conformational flexibility of the HDAC8 loop required for optimal catalytic function. Conclusion: We described a novel Thr119Arg mutation in HDAC8 in a patient displaying the major phenotypic traits of the CdLS. Our results suggest that a modest change outside an active site is capable of triggering global structural changes that propagate through the protein scaffold to the catalytic site, creating de facto haploinsufficiency

Recombinant Alkaline Phosphatase Prevents Acute on Chronic Liver Failure

The lipopolysaccharide (LPS)– toll-like receptor-4 (TLR4) pathway plays an important role in liver failure. Recombinant alkaline phosphatase (recAP) deactivates LPS. The aim of this study was to determine whether recAP prevents the progression of acute and acute-on-chronic liver failure (ACLF). Eight groups of rats were studied 4-weeks after sham surgery or bile duct ligation and were injected with saline or LPS to mimic ACLF. Acute liver failure was induced with Galactosamine-LPS and in both models animals were treated with recAP prior to LPS administration. In the ACLF model, the severity of liver dysfunction and brain edema was attenuated by recAP, associated with reduction in cytokines, chemokines, liver cell death, and brain water. The activity of LPS was reduced by recAP. The treatment was not effective in acute liver failure. Hepatic TLR4 expression was reduced by recAP in ACLF but not acute liver failure. Increased sensitivity to endotoxins in cirrhosis is associated with upregulation of hepatic TLR4, which explains susceptibility to development of ACLF whereas acute liver failure is likely due to direct hepatoxicity. RecAP prevents multiple organ injury by reducing receptor expression and is a potential novel treatment option for prevention of ACLF but not acute liver failure

Boreal forest fires in 1997 and 1998: a seasonal comparison using transport model simulations and measurement data

Forest fire emissions have a strong impact on the concentrations of trace gases and aerosols in the atmosphere. In order to quantify the influence of boreal forest fire emissions on the atmospheric composition, the fire seasons of 1997 and 1998 are compared in this paper. Fire activity in 1998 was very strong, especially over Canada and Eastern Siberia, whereas it was much weaker in 1997. According to burned area estimates the burning in 1998 was more than six times as intense as in 1997. Based on hot spot locations derived from ATSR (Along Track Scanning Radiometer) data and official burned area data, fire emissions were estimated and their transport was simulated with a Lagrangian tracer transport model. Siberian and Canadian forest fire tracers were distinguished to investigate the transport of both separately. The fire emissions were transported even over intercontinental distances. Due to the El Niño induced meteorological situation, transport from Siberia to Canada was enhanced in 1998. Siberian fire emissions were transported towards Canada and contributed concentrations more than twice as high as those due to Canada's own CO emissions by fires. In 1998 both tracers arrive at higher latitudes over Europe, which is due to a higher North Atlantic Oscillation (NAO) index in 1998. The simulated emission plumes are compared to CMDL (Climate Monitoring and Diagnostics Laboratory) CO₂ and CO data, Total Ozone Mapping Spectrometer (TOMS) aerosol index (AI) data and Global Ozone Monitoring Experiment (GOME) tropospheric NO₂ and HCHO columns. All the data show clearly enhanced signals during the burning season of 1998 compared to 1997. The results of the model simulation are in good agreement with ground-based as well as satellite-based measurements

The evolving role of oestrogen receptor beta in clinical breast cancer

Controversy surrounds the potential clinical importance of oestrogen receptor (ER)β in breast cancer, and three recent papers have sought to resolve this. In the present issue of Breast Cancer Research Novelli and colleagues explored the significance of ERβ1 expression in 936 breast cancer patients, and they showed diverse relationships according to lymph node status. A second paper examined 442 breast cancers in which ERβ1 was an independent predictor of recurrence, disease-free survival and overall survival. Finally a third paper showed that ERβ2 was a powerful prognostic indicator in 757 breast cancers but this was dependent on cellular location, with nuclear ERβ2 expression predicting good survival whilst cytoplasmic expression predicted worse outcome. These papers point to a clinical role for ERβ in breast cancer and shall be discussed

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors