Circadian placebo and ACTH effects on urinary cortisol in arthritics

The effect of placebo and ACTH-1-17 (Synchrodyn®, Hoechst) upon urinary free cortisol was examined at 5 different circadian stages on 10 men with Steinbrocker Stage II–III rheumatoid arthritis. A mean cosinor analysis of urinary cortisol data from the subjects prior to treatment with either ACTH or placebo revealed a statistically highly-significant rhythm. A circadian variation in a response of urinary free cortisol to a placebo was also seen. Moreover, the response of the midline-estimating statistic of rhythm (rhythm-adjusted circadian average) of urinary free cortisol to ACTH-1-17 by patients with rheumatoid arthritis is circadian rhythmic. This reactivity rhythm is out of phase with the spontaneous rhythm in urinary cortisol acrophases—in the tests limited thus far to midsummer. The further assessment of the circadian component in the context of broader interactions by rhythms with other frequencies in various conditions in health and disease is warranted by the demonstration of rhythms here presented for men with rheumatoid arthritis.     

Genomewide linkage analysis identifies polymorphism in the human interferon-gamma receptor affecting Helicobacter pylori infection

Helicobacter pylori is considered the most prevalent infectious agent among humans, and it causes gastric inflammation, gastroduodenal ulcers, and a risk of gastric cancer. We performed a genomewide linkage analysis among Senegalese siblings phenotyped for H. pylori-reactive serum immunoglobulin G. A multipoint LOD score of 3.1 was obtained at IFNGR1, the gene that encodes chain 1 of the interferon-gamma (IFN-gamma) receptor. Sequencing of IFNGR1 revealed -56C-->T, H318P, and L450P variants, which were found to be associated with high antibody concentrations. The inclusion of these in the linkage analysis raised the LOD score to 4.2. The variants were more prevalent in Africans than in whites. Our findings indicate that IFN-gamma signaling plays an essential role in human H. pylori infection, and they contribute to an explanation of the observations of high prevalences and relatively low pathogenicity of H. pylori in Africa. Moreover, they provide further support for the value of genomewide linkage studies in the analysis of susceptibility to infection and other complex genetic traits.     

Rhythmic changes in transcriptional activity during the development of potato tubers

Chromatin-bound, DNA-dependent RNA polymerase (EC 2.7.7.6) activity and chromatin template availability, as measured with saturating amounts of E. coli RNA polymerase, changes rhythmically during the formation, dormancy, and sprouting of potato tubers. Active growth processes coincide with the highest RNA polymerase activity as well as the greatest template accessibility, during tuberization and sprouting. Consequently, chromatin-associated RNA and protein content is highest in young developing tubers and in old tubers at the onset of sprouting. Ribosomal RNA content, in turn, is maximal in small tubers, remains constant during dormancy, and decreases when sprouting begins, probably due to the translocation of rRNA into the sprouts. The nucleolus changes its shape and size concomitantly with the process of tuberization.     

The climate of the Younger Dryas as a boundary for Einkorn domestication

The domestication of the Neolithic founder crops of the Near East has recently been a topic of debate particularly with respect to how rapidly the domestication of these crops occurred. One school of thought maintains that these processes lasted several thousand years (‘protracted model’ with ‘gathering’, ‘cultivation’ and ‘domestication’ as three stages of a continuum, each taking up to several thousand years), while another favors the view that domestication occurred much more quickly, over several hundred years at most (‘rapid transition’). Our study focuses on one of these crops, 1-grained domesticated Einkorn wheat, incorporating data from geology, vegetation history, and climate. In the Karacadağ region of southeastern Turkey, where 1-grained Einkorn wheat was domesticated, the climate was severe (i.e. cold and dry) during the Younger Dryas. The climate of the Younger Dryas acted as boundary during which a) conditions were not suitable for ‘cultivation’, and b) Einkorn would have retreated to refugia exhibiting more suitable moisture-bearing soils that would have made ‘gathering’ difficult. Around 11600 cal. b.p., the Younger Dryas ended and a very rapid climatic amelioration commenced at the beginning of the Early Holocene, enabling grasses to spread throughout the region. A ritual PPNA/PPNB site (G?bekli Tepe) and associated PPNB settlements such as Nevali ?ori and ?ay?nü were established at this time. In the settlements of Nevali ?ori and Cafer H?yük, the oldest domesticated Einkorn was found in the earliest archaeological layers. This confirms that the inhabitants made use of domesticated 1-grained Einkorn from the very beginning of settlement activity, although they continued to practice a mixed lifestyle as hunter-gatherers and farmers. For ?ay?nü the issue is more complex, but here domesticated Einkorn also appears around the same time. In summary, by 10400 cal. b.p. domesticated 1-grained Einkorn was present in large quantities at a variety of sites. This would give a maximum window of time lasting approximately 1,200 years and is therefore not in agreement with the ‘protracted’ model but would be consistent with a ‘rapid transition’. It is improbable that the ‘cultivation’ of wild Einkorn was practiced in the Karacadağ region, since wild Einkorn was plentiful during the favorable growing conditions following the Younger Dryas, making it more likely that ‘gathering’ would have been practiced. Because Einkorn has not been found in early settlements in the southern Levant, this crop cannot have been ‘gathered’ and ‘cultivated’ there but instead was ‘domesticated’ independently and solely in southeastern Turkey. Therefore, the YD acts as a boundary, providing a maximum time frame for 1-grained Einkorn domestication.     

A Comparative pO2 Probe and [18F]-Fluoro-Azomycinarabino-Furanoside ([18F]FAZA) PET Study Reveals Anesthesia-Induced Impairment of Oxygenation and Perfusion in Tumor and Muscle

Tumor hypoxia can be identified by [¹⁸F]FAZA positron emission tomography, or invasively using oxygen probes. The impact of anesthetics on tumor hypoxia remains controversial. The aim of this comprehensive study was to investigate the impact of isoflurane and ketamine/xylazine anesthesia on [¹⁸F]FAZA uptake and partial oxygen pressure (pO₂) in carcinoma and muscle tissue of air- and oxygen-breathing mice.

Methods

CT26 colon carcinoma-bearing mice were anesthetized with isoflurane (IF) or ketamine/xylazine (KX) while breathing air or oxygen (O₂). We performed 10 min static PET scans 1 h, 2 h and 3 h after [¹⁸F]FAZA injection and calculated the [¹⁸F]FAZA-uptake and tumor-to-muscle ratios (T/M). In another experimental group, we placed a pO₂ probe in the tumor as well as in the gastrocnemius muscle to measure the pO₂ and perfusion.

Results

Ketamine/xylazine-anesthetized mice yielded up to 3.5-fold higher T/M-ratios compared to their isoflurane-anesthetized littermates 1 h, 2 h and 3 h after [¹⁸F]FAZA injection regardless of whether the mice breathed air or oxygen (3 h, KX-air: 7.1 vs. IF-air: 1.8, p = 0.0001, KX-O₂: 4.4 vs. IF-O₂: 1.4, p < 0.0001). The enhanced T/M-ratios in ketamine/xylazine-anesthetized mice were mainly caused by an increased [¹⁸F]FAZA uptake in the carcinomas. Invasive pO₂ probe measurements yielded enhanced intra-tumoral pO₂ values in air- and oxygen-breathing ketamine/xylazine-anesthetized mice compared to isoflurane-anesthetized mice (KX-air: 1.01 mmHg, IF-air: 0.45 mmHg; KX-O₂ 9.73 mmHg, IF-O₂: 6.25 mmHg). Muscle oxygenation was significantly higher in air-breathing isoflurane-anesthetized (56.9 mmHg) than in ketamine/xylazine-anesthetized mice (33.8 mmHg, p = 0.0003).

Conclusion

[¹⁸F]FAZA tumor uptake was highest in ketamine/xylazine-anesthetized mice regardless of whether the mice breathed air or oxygen. The generally lower [¹⁸F]FAZA whole-body uptake in isoflurane-anesthetized mice could be due to the higher muscle pO₂-values in these mice compared to ketamine/xylazine-anesthetized mice. When performing preclinical in vivo hypoxia PET studies, oxygen should be avoided, and ketamine/xylazine-anesthesia might alleviate the identification of tumor hypoxia areals.     

Neural Control of Enhanced Filtering Demands in a Combined Flanker and Garner Conflict Task

Several studies demonstrated that visual filtering mechanisms might underlie both conflict resolution of the Flanker conflict and the control of the Garner effect. However, it remains unclear whether the mechanisms involved in the processing of both effects depend on similar filter mechanisms, such that especially the Garner effect is able to modulate filtering needs in the Flanker conflict. In the present experiment twenty-four subjects participated in a combined Garner and Flanker task during two runs of functional magnetic resonance imaging (fMRI) recordings. Behavioral data showed a significant Flanker but no Garner effect. A run-wise analysis, however, revealed a Flanker effect in the Garner filtering condition in the first experimental run, while we found a Flanker effect in the Garner baseline condition in the second experimental run. The fMRI data revealed a fronto-parietal network involved in the processing of both types of effects. Flanker interference was associated with activity in the inferior frontal gyrus, the anterior cingulate cortex, the precuneus as well as the inferior (IPL) and superior parietal lobule (SPL). Garner interference was associated with activation in middle frontal and middle temporal gyrus, the lingual gyrus as well as the IPL and SPL. Interaction analyses between the Garner and the Flanker effect additionally revealed differences between the two experimental runs. In the first experimental run, activity specifically related to the interaction of effects was found in frontal and parietal regions, while in the second run we found activity in the hippocampus, the parahippocampal cortex and the basal ganglia. This shift in activity for the interaction effects might be associated with a task-related learning process to control filtering demands. Especially perceptual learning mechanisms might play a crucial role in the present Flanker and Garner task design and, therefore, increased performance in the second experimental run could be the reason for the lack of behavioral Garner interference on the level of the whole experiment.     

Fetal and early post-natal development of the human spleen: from primordial arterial B cell lobules to a non-segmented organ

Immunohistological analysis of 31 human spleens from the 11th week of gestation to the early postnatal period suggested that fetal organ development may be preliminarily divided into four stages. At stage 0 the organ anlage contained erythrocyte precursors, few macrophages and almost no lymphocytes. Fetal spleens of stage I exhibited arterial vascular lobules and lymphocytes just began colonizing the organ. At stage II, B and T lymphocytes formed periarteriolar clusters. B cell clusters predominated, because B cells aggregated around the more peripheral branches of splenic arterioles, while T cells occupied the more centrally located parts of the vessels. The vascular lobules of stage I and II consisted of central arterioles surrounded by B cells, capillaries and peripheral venules. The lobular architecture slowly dissolved at late stage II when sinuses grew out from the peripheral venules into the centre of the lobule. Interestingly, the B cell accumulations around peripheral arterioles did not represent the precursors of follicles, but apparently persisted as periarteriolar B cell clusters in the adult splenic red pulp, while follicles containing FDCs developed at late stage II from B cells in direct contact to T cell clusters around larger arterial vessels. At stage III before birth the lobular architecture was no longer recognized. The chemokine CXCL13 was already present in vascular smooth muscle and adjacent stromal cells at stage I before B cells immigrated. CCL21, on the contrary, was only demonstrated in fibroblast-like cells supporting T cell clusters from stage II onwards.     

Complete genome sequence of Ignisphaera aggregans type strain (AQ1.S1)

Ignisphaera aggregans Niederberger et al. 2006 is the type and sole species of genus Ignisphaera. This archaeal species is characterized by a coccoid-shape and is strictly anaerobic, moderately acidophilic, heterotrophic hyperthermophilic and fermentative. The type strain AQ1.S1(T) was isolated from a near neutral, boiling spring in Kuirau Park, Rotorua, New Zealand. This is the first completed genome sequence of the genus Ignisphaera and the fifth genome (fourth type strain) sequence in the family Desulfurococcaceae. The 1,875,953 bp long genome with its 2,009 protein-coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.