Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C

Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes

Aims Inflammation plays a key role in acute coronary syndromes (ACS). Toll-like receptors (TLR) on leucocytes mediate inflammation and immune responses. We characterized leucocytes and TLR expression within coronary thrombi and compared cytokine levels from the site of coronary occlusion with aortic blood (AB) in ACS patients. Methods and results In 18 ACS patients, thrombi were collected by aspiration during primary percutaneous coronary intervention. Thrombi and AB from these patients as well as AB from 10 age-matched controls without coronary artery disease were assessed by FACS analysis for cellular distribution and TLR expression. For further discrimination of ACS specificity, seven non-coronary intravascular thrombi and eight thrombi generated in vitro were analysed. In 17 additional patients, cytokine levels were determined in blood samples from the site of coronary occlusion under distal occlusion and compared with AB. In coronary thrombi from ACS, the percentage of monocytes related to the total leucocyte count was greater than in AB (47 vs. 20%, P = 0.0002). In thrombi, TLR-4 and TLR-2 were overexpressed on CD14-labelled monocytes, and TLR-2 was increased on CD66b-labelled granulocytes, in comparison with leucocytes in AB. In contrast, in vitro and non-coronary thrombi exhibited no overexpression of TLR-4. Local blood samples taken under distal occlusion revealed elevated concentrations of chemokines (IL-8, MCP-1, eotaxin, MIP-1α, and IP-10) and cytokines (IL-1ra, IL-6, IL-7, IL-12, IL-17, IFN-α, and granulocyte-macrophage colony-stimulating factor) regulating both innate and adaptive immunity (all P < 0.05). Conclusion In ACS patients, monocytes accumulate within thrombi and specifically overexpress TLR-4. Together with the local expression patterns of chemokines and cytokines, the increase of TLR-4 reflects a concerted activation of this inflammatory pathway at the site of coronary occlusion in AC

Systematics of proton emission

A very simple formula is presented that relates the logarithm of the half-life, corrected by the centrifugal barrier, with the Coulomb parameter in proton decay processes. The corresponding experimental data lie on two straight lines which appear as a result of a sudden change in the nuclear shape marking two regions of deformation independently of the angular momentum of the outgoing proton. This feature provides a powerful tool to assign experimentally quantum numbers in proton emitters.Comment: 4 pages, 3 figure

Psychiatric Symptom Profiles Predict Functional Impairment

Objective: Mental illness often interferes with daily functioning and an individual's pattern of psychiatric signs and symptoms may predict risk of future disability. Understanding the linkage between psychiatric symptoms and impaired functioning is critical for accurate rehabilitation planning and legal assessment. Here, we investigated the stability of functional impairment measures over 18 months and their association with psychiatric symptoms. Moreover, we developed a clinical self-report measure that allows estimation of functional impairment levels over 18 month observation periods.Methods: Consecutively treated outpatients and daycare patients (N = 155) from several psychiatric units in Switzerland completed the Dissociative Experiences Scale, Somatoform Dissociation Questionnaire, Multidimensional Inventory for Dissociation, Beck Depression Inventory, Brief Symptom Inventory, and WHO Disability Assessment Schedule at baseline, 6, 12, and 18 month follow-up examinations. The association between symptoms functional impairment over time was investigated using longitudinal linear mixed models. Penalized regression was used to identify questionnaire items that best predicted functional impairment.Results: We found high stability in the extent of functional impairment over 18 months. Fear of negative evaluation, fatigue, concentration problems, negative alterations in mood, and dissociative symptoms showed the strongest association with functional impairment measures. The empirically derived scale for functional impairment prediction explained between 0.62 and 0.77 of the variance in disability across various life domains.Conclusion: Given the capability for somatic and mental symptoms associated with social anxiety, depression, and dissociation to predict future disability, these symptoms have strong potential for guiding rehabilitation planning and prognostic evaluation in insurance medicine. The Functional Impairment Prediction Scale may serve as a valuable, empirical-based extension in legal assessments of how work capacity is affected by psychological factors

Ecological conditions for Saxifraga hirculus in Central Europe: a better understanding for a good protection

Saxifraga hirculus is a postglacial relict in Central Europe, whose populations suffered a dramatic decrease in the 19th and 20th centuries. However, few researchers have been interested in its ecological requirements in Central Europe. This article synthesizes previous knowledge supplemented by original data from the last large population (Switzerland). S. hirculus is a weak competitor which needs precise ecological conditions. It grows on bryophyte carpets in neutral to slightly acid wetlands, with stable water table close to the soil surface (optimum between 8-14 cm) but does not stand long flooding. However, it requires a good oxygen supply, with roots 2-3 cm under the soil surface, generally not reached by water, with running, cold water through loose, fibric peat. Its optimal conditions are in spring fens, but it grows in other types of wetlands as well. However, overgrowing by shrubs, sedges or Sphagnum in natural successions may threaten the species with extinction, as did drainage and peat extraction previously. Now, its survival in Central Europe depends on an adequate management of the ecosystems. Moderate grazing (cattle or sheep) or mowing help to limit competition with taller Carex species. Re-introduction of disappeared populations or creation of new ones from cultivation in botanical garden is possible, but appropriate sites are rare. In some cases, substrate management could improve the conditions in somewhat inadequate situations. This management in four directions can be flexibly applied in different situations to progress to optimal conditions for the conservation of this valuable species

Frequency of malaria and glucose-6-phosphate dehydrogenase deficiency in Tajikistan

BACKGROUND: During the Soviet era, malaria was close to eradication in Tajikistan. Since the early 1990s, the disease has been on the rise and has become endemic in large areas of southern and western Tajikistan. The standard national treatment for Plasmodium vivax is based on primaquine. This entails the risk of severe haemolysis for patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Seasonal and geographical distribution patterns as well as G6PD deficiency frequency were analysed with a view to improve understanding of the current malaria situation in Tajikistan. METHODS: Spatial and seasonal distribution was analysed, applying a risk model that included key environmental factors such as temperature and the availability of mosquito breeding sites. The frequency of G6PD deficiency was studied at the health service level, including a cross-sectional sample of 382 adult men. RESULTS: Analysis revealed high rates of malaria transmission in most districts of the southern province of Khatlon, as well as in some zones in the northern province of Sughd. Three categories of risk areas were identified: (i) zones at relatively high malaria risk with high current incidence rates, where malaria control and prevention measures should be taken at all stages of the transmission cycle; (ii) zones at relatively high malaria risk with low current incidence rates, where malaria prevention measures are recommended; and (iii) zones at intermediate or low malaria risk with low current incidence rates where no particular measures appear necessary. The average prevalence of G6PD deficiency was 2.1% with apparent differences between ethnic groups and geographical regions. CONCLUSION: The study clearly indicates that malaria is a serious health issue in specific regions of Tajikistan. Transmission is mainly determined by temperature. Consequently, locations at lower altitude are more malaria-prone. G6PD deficiency frequency is too moderate to require fundamental changes in standard national treatment of cases of P. vivax

Forum: conflict delegation in civil wars

This forum provides an outlet for an assessment of research on the delegation of war to non-state armed groups in civil wars. Given the significant growth of studies concerned with this phenomenon over the last decade, this forum critically engages with the present state of the field. First, we canvass some of the most important theoretical developments to demonstrate the heterogeneity of the debate. Second, we expand on the theme of complexity and investigate its multiple facets as a window into pushing the debate forward. Third, we draw the contours of a future research agenda by highlighting some contemporary problems, puzzles, and challenges to empirical data collection. In essence, we seek to connect two main literatures that have been talking past each other: external support in civil wars and proxy warfare. The forum bridges this gap at a critical juncture in this new and emerging scholarship by offering space for scholarly dialogue across conceptual labels

Early Neurodegeneration Progresses Independently of Microglial Activation by Heparan Sulfate in the Brain of Mucopolysaccharidosis IIIB Mice

BACKGROUND: In mucopolysaccharidosis type IIIB, a lysosomal storage disease causing early onset mental retardation in children, the production of abnormal oligosaccharidic fragments of heparan sulfate is associated with severe neuropathology and chronic brain inflammation. We addressed causative links between the biochemical, pathological and inflammatory disorders in a mouse model of this disease. METHODOLOGY/PRINCIPAL FINDINGS: In cell culture, heparan sulfate oligosaccharides activated microglial cells by signaling through the Toll-like receptor 4 and the adaptor protein MyD88. CD11b positive microglial cells and three-fold increased expression of mRNAs coding for the chemokine MIP1alpha were observed at 10 days in the brain cortex of MPSIIIB mice, but not in MPSIIIB mice deleted for the expression of Toll-like receptor 4 or the adaptor protein MyD88, indicating early priming of microglial cells by heparan sulfate oligosaccharides in the MPSIIIB mouse brain. Whereas the onset of brain inflammation was delayed for several months in doubly mutant versus MPSIIIB mice, the onset of disease markers expression was unchanged, indicating similar progression of the neurodegenerative process in the absence of microglial cell priming by heparan sulfate oligosaccharides. In contrast to younger mice, inflammation in aged MPSIIIB mice was not affected by TLR4/MyD88 deficiency. CONCLUSIONS/SIGNIFICANCE: These results indicate priming of microglia by HS oligosaccharides through the TLR4/MyD88 pathway. Although intrinsic to the disease, this phenomenon is not a major determinant of the neurodegenerative process. Inflammation may still contribute to neurodegeneration in late stages of the disease, albeit independent of TLR4/MyD88. The results support the view that neurodegeneration is primarily cell autonomous in this pediatric disease