Selective IgA Deficiency

Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency

Imaging and imagination: understanding the endo-lysosomal system

Lysosomes are specialized compartments for the degradation of endocytosed and intracellular material and essential regulators of cellular homeostasis. The importance of lysosomes is illustrated by the rapidly growing number of human disorders related to a defect in lysosomal functioning. Here, we review current insights in the mechanisms of lysosome biogenesis and protein sorting within the endo-lysosomal system. We present increasing evidence for the existence of parallel pathways for the delivery of newly synthesized lysosomal proteins directly from the trans-Golgi network (TGN) to the endo-lysosomal system. These pathways are either dependent or independent of mannose 6-phosphate receptors and likely involve multiple exits for lysosomal proteins from the TGN. In addition, we discuss the different endosomal intermediates and subdomains that are involved in sorting of endocytosed cargo. Throughout our review, we highlight some examples in the literature showing how imaging, especially electron microscopy, has made major contributions to our understanding of the endo-lysosomal system today

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology

Failure stress change caused by the 1992 Erzincan earthquake (Ms=6.8)

We calculated Coulomb failure stress change caused by the March 13, 1992 Erzincan, Turkey, earthquake, and explored the relationship between failure stress and the aftershock distribution which includes the Pulumur earthquake (Ms=5.8) that occurred two days later. One of the most significant features of the Erzincan earthquake was the location of aftershocks, which did not correspond with either the eastern segment of the North Anatolian fault zone or the Ovacik fault. This feature can be explained by mapping the failure stress due to the Erzincan earthquake. The map revealed that there is a significant correlation between the aftershock distribution and the areas where static stress was raised by greater than or equal to 0.3 bar. The 1992 Erzincan earthquake raised the Coulomb failure stress about 1.4 bar at the site of the Pulumur event. This stress rise and optimum orientation of the Pulumur fault favoured its occurrence

Stress accumulation and increased seismic risk in eastern Turkey

Unlike the North Anatolian fault zone, which has produced 11 large earthquakes since 1939, the East Anatolian fault zone (EAFZ) has been relatively quiescent in the last century when compared to historical records and has therefore accumulated significant stresses along its length. Determination of the location and likely magnitude of a future probable earthquake along the EAFZ is of interest both because of this history of large earthquakes, (M approximate to 8), and the density of population in the area. Here we calculate stress evolution along the fault zone due to both seismic and tectonic loading since 1822. A sequence of 10 well constrained historical earthquakes is selected and the resulting stresses are calculated, summed with tectonic loading stresses and resolved onto the mapped active faults. We identify two areas of particular seismic risk, one of which might be expected to yield a large event. Our results are sensitive to the previous history of large earthquakes in the region and indicate a need for detailed investigations to constrain the exact rupture geometries of previous earthquakes on these segments. (C) 2002 Elsevier Science B.V. All rights reserved

Palaeoseismic history of the eastern part of the North Anatolian Fault (Erzincan, Turkey): Implications for the seismicity of the Yedisu seismic gap

The North Anatolian Fault showed a remarkable seismic activity especially between 1939 and 1999, when the westward migrating earthquake sequence created surface ruptures more than 1000 km, leaving unbroken only the Marmara segments, to the west, and the Yedisu Segment, to the east along the main strand of the fault. To understand the palaeoseismicity of the Yedisu Seismic Gap, we undertook trench investigations close to the village of Balaban Sarıkaya, on the western part of the Yedisu Segment. We found evidence for at least five surface faulting earthquakes, from which only two are correlated with the 18 July 1784 CE and 27 June 1583 CE historical events. Although the surface rupture of the 1784 CE was reported by other trench studies, the evidence of 1583 CE event is presented for the first time. In consideration with other historical earthquakes, affecting the region east of Erzincan, we suggest that this particular section of the North Anatolian Fault may be in a seismically quiescent period, following a cluster of earthquakes in its near history. In order to test this hypothesis, further studies are needed to increase our knowledge on the temporal and spatial seismic behaviour of the Yedisu Segment, which has potential to create an earthquake with Mw ~7.2 in the near futur