Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis—a review

This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin β2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction

Inventory, distribution and topographic features of rock glaciers in the southern region of the Eastern Italian Alps (Trentino)

A GIS-based rock glacier inventory was conducted in a region of about 6200 km2 located in the southern sector of the Eastern Italian Alps (Trentino). The rock glaciers cover a total area of 33.3 km2, which is more than 1.4% of the area located above 1600 m a.s.l. and is comparable to the area covered by glaciers (38.3 km2 in 2003). The rock glaciers are located at a mean elevation of 2282 ±289 m a.s.l. and are distributed in an elevation range of about 1440 m. Considering separately the two classes of intact and relict (i.e. with no permafrost) rock glaciers, the mean elevation is 2632 ±205 m a.s.l. and 2169 ±211 m a.s.l. respectively. Relict rock glaciers are found between 1650 and 2700 m a.s.l., whereas above 2800 m a.s.l. only intact rock glaciers exist. The mean aspect of all the inventoried rock glaciers is 43°. A dominant northern orientation does not emerge in the class of the intact forms, whereas the relict rock glaciers show a predominant northern orientation with a mean aspect of about 30°. According to the mean elevation of the intact rock glaciers, the lower boundary of permafrost in the studied region would be located at an elevation of approximately 2630 m a.s.l. This boundary varies significantly when considering the different exposures, and ranges from about 2510 m a.s.l. on north-facing slopes to about 2690 m a.s.l. on those exposed to the south. The lower boundary of permafrost existence in the past, as marked by the mean altitude of the relict rock glaciers, was located about 450 m lower than the modern one with variations included in a range of 230 m according to the exposure. This provides a rough estimation of the shift in elevation of the lower permafrost boundary between the present-day and the time when the relict rock glaciers were active. Accordingly, a MAAT increase of about 2.9°C can be calculated applying a standard vertical lapse rate (0.65°C/100 m) to this shift

Chapter 4: Local ground movements and effects on infrastructures

Local ground movements may be defined as phenomena of instability that affect slopes or flat ground in a surface of hundreds to thousands of square meters. Local ground movements are a common feature in permafrost areas, and include: •Horizontal downslope movements, due to the creep of permafrost bodies. •Vertical settling movements, due to the melting of ice bodies and/or interstitial ice. These movements may cause damages to buildings and infrastructures or more rarely represent a hazard for persons: •Damages to buildings are mainly due to differential settling of the ground. Some mountain huts are endangered by the collapse of the rock foundations. •Cableways are the most common and sensible infrastructures in alpine permafrost areas. Movements of pylons and of start and end stations lead to problems of cable alignement. It induces increased maintenance costs, and reduces the lifetime of the investment. •The stability of hazard protection infrastructures can be changelled by permafrost degradation. •Thermokarst phenomena due to the removal or compaction of the surface layer can cause substantial damage to planation works like ski tracks or roads. In many cases, it must be emphasized that the infrastructure may induce itself the degradation of the undelying permafrost, through heat conduction by the infrastructure, or through the modification of the insulation capacity of the ground. An adapted conception of the infrastructure can, in many cases, avoid both the influence on the permafrost state and damages due to movements. When planning an infrastructure in a high mountain environement (e.g. above 2400 m), the possible presence of permafrost should always be investigated prior to the conception. The permafrost distribution map can give a first indication. Geophysical methods permit to detect the possible occurrence of frozen ground. But only a drilling can give reliable information on the presence and thickness of ground ice. Monitoring of temperature and movements during at least one year will give more informations on potential surface movements. If permafrost is present, an adapted design should be developped, such as: •A thermal insulation in order to avoid heat transmission from buildings into the frozen ground. •Adapted foundations in order to accommodate movements. Arctic countries have a long experience in adapted design of infrastructures. Guidelines for building on mountain permafrost were edited by Swiss authorities

A retrospective study of focal segmental glomerulosclerosis: clinical criteria can identify patients at high risk for recurrent disease after first renal transplantation

Contains fulltext : 118458.pdf (publisher's version ) (Open Access)BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a frequent cause of end-stage renal disease. Renal transplantation in patients with FSGS is often complicated by disease recurrence, which is associated with poor outcome. There are no tests that reliably predict recurrence of FSGS after transplantation. The aim of this study was to evaluate if clinical criteria can identify patients at high risk for recurrent disease. METHODS: We retrospectively studied 94 patients who received a first renal transplant at a median age of 37 years (range 5-69 years). Patients were assigned to one of three groups: familial or genetic FSGS (group I; n=18), secondary FSGS (group II; n=10) and idiopathic FSGS (group III; n=66). Pretransplant clinical characteristics were analyzed to determine predictors of a recurrence after transplantation. RESULTS: FSGS only recurred in patients with idiopathic FSGS (group III; 42%). Patients with a recurrence had a significantly lower serum albumin, higher 24-hour proteinuria and higher estimated glomerular filtration rate at diagnosis. Serum albumin at diagnosis was the only independent predictor of a recurrence in patients with idiopathic FSGS. Patients with recurrent FSGS had more acute rejection episodes (54% vs. 27%, P =0.02) and lower five year graft survival compared to patients without a recurrence (50 vs. 82%, P <0.01). CONCLUSIONS: Clinical criteria allow identification of patients at high risk of recurrent FSGS after renal transplantation. This information can be used in the counseling and management of patients with FSGS

Rockglaciers of the Engadine

The Engadine is one of the rockglacier hot spots in the European Alps. Many rockglaciers in all states of activity (active, inactive, relict) are found, indicating the former and present occurrence of permafrost. This is due to continental climate conditions, high elevation, and high weathering rates. Rockglaciers are developed in valley bottoms, such as the Val Sassa and the Val da l’Acqua rockglacier, or in formerly glaciated cirques, such as the Muragl or the Murtèl rockglacier. Hence, the Engadine is the home of research on rockglaciers in Europe with the first studies on rockglaciers of the Swiss National Park one century ago. Engadine was also the first place in the world where boreholes in rockglaciers were drilled in 1987. Nowadays, several Engadine rockglaciers are monitored within the Permafrost Monitoring Network Switzerland (PERMOS)

Stratospheric temperature trends: impact of ozone variability and the QBO

In most climate simulations used by the Intergovernmental Panel on Climate Change 2007 fourth assessment report, stratospheric processes are only poorly represented. For example, climatological or simple specifications of time-varying ozone concentrations are imposed and the quasi-biennial oscillation (QBO) of equatorial stratospheric zonal wind is absent. Here we investigate the impact of an improved stratospheric representation using two sets of perturbed simulations with the Hadley Centre coupled ocean atmosphere model HadGEM1 with natural and anthropogenic forcings for the 1979–2003 period. In the first set of simulations, the usual zonal mean ozone climatology with superimposed trends is replaced with a time series of observed zonal mean ozone distributions that includes interannual variability associated with the solar cycle, QBO and volcanic eruptions. In addition to this, the second set of perturbed simulations includes a scheme in which the stratospheric zonal wind in the tropics is relaxed to appropriate zonal mean values obtained from the ERA-40 re-analysis, thus forcing a QBO. Both of these changes are applied strictly to the stratosphere only. The improved ozone field results in an improved simulation of the stepwise temperature transitions observed in the lower stratosphere in the aftermath of the two major recent volcanic eruptions. The contribution of the solar cycle signal in the ozone field to this improved representation of the stepwise cooling is discussed. The improved ozone field and also the QBO result in an improved simulation of observed trends, both globally and at tropical latitudes. The Eulerian upwelling in the lower stratosphere in the equatorial region is enhanced by the improved ozone field and is affected by the QBO relaxation, yet neither induces a significant change in the upwelling trend