Age-related maculopathy : linking aetiology and pathophysiological changes to the ischaemia hypothesis

Age-related maculopathy (ARM) has remained a challenging topic with respect to its aetiology, pathomechanisms, early detection and treatment since the late 19th century when it was first described as its own entity. ARM was previously considered an inflammatory disease, a degenerative disease, a tumor and as the result of choroidal hemodynamic disturbances and ischaemia. The latter processes have been repeatedly suggested to have a key role in its development and progression. In vivo experiments under hypoxic conditions could be models for the ischaemic deficits in ARM. Recent research has also linked ARM with gene polymorphisms. It is however unclear what triggers a person's gene susceptibility. In this manuscript, a linking hypothesis between aetiological factors including ischaemia and genetics and the development of early clinicopathological changes in ARM is proposed. New clinical psychophysical and electrophysiological tests are introduced that can detect ARM at an early stage. Models of early ARM based upon hemodynamic, photoreceptor and post-receptoral deficits are described and the mechanisms by which ischaemia may be involved as a final common pathway are considered. In neovascular age-related macular degeneration (neovascular AMD), ischaemia is thought to promote release of vascular endothelial growth factor (VEGF) which induces chorioretinal neovascularisation. VEGF is critical in the maintenance of the healthy choriocapillaris. In the final section of the manuscript the documentation of the effect of new anti-VEGF treatments on retinal function in neovascular AMD is critically viewed.

Vegetation history, human impact and climate change during prehistory: an island perspective of the isles of Tiree, Coll and north-west Mull

Results of extensive site reconnaissance on the Isles of Tiree, Coll and north-west Mull, Inner Hebrides are presented. Pollen-stratigraphic records were compiled from a profile from Glen Aros, north-west Mull and from two profiles on Coll located at Loch an t-Sagairt and Caolas an Eilean. Quantification of microscopic charcoal provided records that were used to facilitate a preliminary evaluation of the causal driving mechanisms of vegetation change. Bayesian modelling of radiocarbon dates was used to construct preliminary chronological frameworks for these records. Basal sedimentary deposits at Glen Aros contain pollen records that correspond with vegetation succession typical of the early Holocene dating to c. 11,370 cal BP. Woodland development is a key feature of the pollen records dating to the early Holocene, while records from Loch an t-Sagairt show that blanket mire communities were widespread in north-west Coll by c. 9800 cal BP. The Corylus-rise is dated to c. 10,710 cal BP at Glen Aros and c. 9905 cal BP at Loch an t-Sagairt, with records indicating extensive cover of hazel woodland with birch. All of the major arboreal taxa were recorded, though Quercus and Ulmus were nowhere widespread. Analysis of wood charcoal remains from a Mesolithic site at Fiskary Bay, Coll indicate that Salix and Populus are likely to be under-represented in the pollen records. Reconstructed isopoll maps appear to underplay the importance of alder in western Scotland during the mid-Holocene. Alder-rise expansions in microscopic charcoal dating to c. 7300 cal BP at Glen Aros and c. 6510 to 5830 cal BP on Coll provide records of significance to the issue of human-induced burning related to the expansion of alder in Britain. Increasing frequencies in microscopic charcoal are correlated with mid-Holocene records of increasing aridity in western Scotland after c. 7490 cal BP at Glen Aros, 6760 cal BP at Loch an t-Sagairt and 6590 cal BP at Caolas an Eilean, while several phases of increasing bog surface wetness were detected in the Loch an t-Sagairt archive during the Holocene. At least five phases of small-scale woodland disturbance during the Mesolithic period were identified in the Glen Aros profile dating to c. 11,650 cal BP, 9300 cal BP, 7840 cal BP, 7040 cal BP and 6100 cal BP. The timing of the third phase is coincident with evidence of Mesolithic settlement at Creit Dhu, north-west Mull. Three phases of small-scale woodland disturbance were detected at Loch an t-Sagairt dating to c. 9270 cal BP, 8770 cal BP and 8270 cal BP, all of which overlap chronologically with evidence of Mesolithic activity at Fiskary Bay, Coll. A number of these episodes are aligned chronologically with phases of Holocene climate variability such as the 8.2 K event.

Aspectos histológicos e morfométricos da pele de cães do nascimento aos 70 dias de idade, clinicamente saudáveis

Pós-graduação em Medicina Veterinária - FMVZ

The Regulation of AMD Pathobiology by Complement Factor H

Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/- and Cfh-/- mice fed a high fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (RPE) deposit formation, specifically basal laminar deposits, following high fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/- and Cfh-/- mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/- mice. We demonstrate that such pathology is a function of excess complement activation and C5a production, associated with monocyte recruitment, in Cfh+/- mice versus complement deficiency in Cfh-/- animals. Due to the CFH dependent increase in sub-RPE deposit height we interrogated the potential of CFH as a novel regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Interestingly, although the CFH H402 variant shows altered binding to BrM, this does not affect its ability to remove endogenous lipoproteins. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD.

Submarine pyroclastic deposits formed at the Soufrière Hills volcano, Montserrat (1995–2003) : what happens when pyroclastic flows enter the ocean?

The Soufrière Hills volcano, Montserrat, West Indies, has undergone a series of dome growth and collapse events since the eruption began in 1995. Over 90% of the pyroclastic material produced has been deposited into the ocean. Sampling of these submarine deposits reveals that the pyroclastic flows mix rapidly and violently with the water as they enter the sea. The coarse components (pebbles to boulders) are deposited proximally from dense basal slurries to form steep-sided, near-linear ridges that intercalate to form a submarine fan. The finer ash-grade components are mixed into the overlying water column to form turbidity currents that flow over distances >30 km from the source. The total volume of pyroclastic material off the east coast of Montserrat exceeds 280 × 106 m3, with 65% deposited in proximal lobes and 35% deposited as distal turbidites.

Detection of linear IgE deposits in bullous pemphigoid and mucous membrane pemphigoid: a useful clue for diagnosis

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease of the skin associated with IgG autoantibodies to BP180 and BP230, while mucous membrane pemphigoid (MMP) comprises a heterogeneous group of autoimmune blistering diseases characterized by a predominant mucous membrane involvement and scarring tendency associated with an autoantibody response to various autoantigens, including BP180. While the pathogenicity of IgG autoantibodies to BP180 has been demonstrated in BP, the role of IgE autoantibodies in mediating tissue damage in BP and MMP is unclear.

Spatial pattern analysis of beta-amyloid (A beta) deposits in Alzheimer disease by linear regression

The spatial patterns of discrete beta-amyloid (Abeta) deposits in brain tissue from patients with Alzheimer disease (AD) were studied using a statistical method based on linear regression, the results being compared with the more conventional variance/mean (V/M) method. Both methods suggested that Abeta deposits occurred in clusters (400 to <12,800 mu m in diameter) in all but 1 of the 42 tissues examined. In many tissues, a regular periodicity of the Abeta deposit clusters parallel to the tissue boundary was observed. In 23 of 42 (55%) tissues, the two methods revealed essentially the same spatial patterns of Abeta deposits; in 15 of 42 (36%), the regression method indicated the presence of clusters at a scale not revealed by the V/M method; and in 4 of 42 (9%), there was no agreement between the two methods. Perceived advantages of the regression method are that there is a greater probability of detecting clustering at multiple scales, the dimension of larger Abeta clusters can be estimated more accurately, and the spacing between the clusters may be estimated. However, both methods may be useful, with the regression method providing greater resolution and the V/M method providing greater simplicity and ease of interpretation. Estimates of the distance between regularly spaced Abeta clusters were in the range 2,200-11,800 mu m, depending on tissue and cluster size. The regular periodicity of Abeta deposit clusters in many tissues would be consistent with their development in relation to clusters of neurons that give rise to specific neuronal projections.

Annotated record of the detailed examination of Mn deposits from DSDP Site 32, Leg 5 (Cores 5-32-13, 5-32-14)

Site 32 was proposed by the Pacific Advisory Panel at a location over a strong positive magnetic anomaly (Number 13 on the Pittman-Heirtzler scale, 38 million years) where samples of the basement and the basal sediment would be of value in testing hypotheses for origin of the linear magnetic anomalies from this part of the Pacific. Comparison of this site, south of the Pioneer Fracture Zone, with later sites north of the Fracture Zone would be the basis for evaluating the discontinuity formed by the Pioneer.

Submarine pyroclastic deposits formed during the 20th May 2006 dome collapse of the Soufrière Hills Volcano, Montserrat

The 20th May 2006 lava dome collapse of the Soufrière Hills Volcano, Montserrat, had a total non-dense rock equivalent (non-DRE) collapse volume of approximately 115 × 10 6 m 3. The majority of this volume was deposited into the ocean. The collapse was rapid, 85% of the mobilized volume being removed in just 35 min, giving peak pyroclastic flow flux of 66 × 10 3 m 3 s -1. Channel and levee facies on the submarine flanks of the volcano and formation of a thick, steep-sided ridge, suggest that the largest and most dense blocks were transported proximally as a high concentration granular flow. Of the submerged volume, 30% was deposited from the base of this granular flow, forming a linear, high-relief ridge that extends 7 km from shore. The remaining 70% of the submerged volume comprises the finer grain sizes, which were transported at least 40 km by turbidity currents on gradients of <2°. At several localities, the May 2006 distal turbidity currents ran up 200 m of topography and eroded up to 20 cm of underlying substrate. Multiple turbidites are preserved, representing current reflection from the graben margins and deflection around topography. The high energy of the May 2006 collapse resulted in longer submarine run out than the larger (210 × 10 6 m 3) Soufrière Hills dome collapse in July 2003.

Emplacement of pyroclastic deposits offshore Montserrat : insights from 3D seismic data

During the current (1995-present) eruptive phase of the Soufrière Hills volcano on Montserrat, voluminous pyroclastic flows entered the sea off the eastern flank of the island, resulting in the deposition of well-defined submarine pyroclastic lobes. Previously reported bathymetric surveys documented the sequential construction of these deposits, but could not image their internal structure, the morphology or extent of their base, or interaction with the underlying sediments. We show, by combining these bathymetric data with new high-resolution three dimensional (3D) seismic data, that the sequence of previously detected pyroclastic deposits from different phases of the ongoing eruptive activity is still well preserved. A detailed interpretation of the 3D seismic data reveals the absence of significant (> 3. m) basal erosion in the distal extent of submarine pyroclastic deposits. We also identify a previously unrecognized seismic unit directly beneath the stack of recent lobes. We propose three hypotheses for the origin of this seismic unit, but prefer an interpretation that the deposit is the result of the subaerial flank collapse that formed the English's Crater scarp on the Soufrière Hills volcano. The 1995-recent volcanic activity on Montserrat accounts for a significant portion of the sediments on the southeast slope of Montserrat, in places forming deposits that are more than 60. m thick, which implies that the potential for pyroclastic flows to build volcanic island edifices is significant.

晚中新世以来中国北方风成沉积的磁性地层学和沉积学研究

The past two decades have witnessed an unprecedented growth of interest in the palaeoenvironmental significance of the Pleistocene loess deposits in northern China. However, it is only several years ago that the Tertiary red clay sequence underlying Pleistocene loess attracted much attention. One of the major advances in recent studies of eolian deposits on the Loess Plateau is the verification of the eolian origin for the Tertiary red clay sediments. The evidence of the eolian origin for the red clay is mainly from geochemical and sedimentological studies. However, sedimentological studies of the red clay deposits are still few compared with those of the overlying loess sediments. To date, the red clay sections located near Xifeng, Baoji, Lantian, Jiaxian, and Lingtai have been studied, with an emphasis on magnetostratigraphy. These sections have a basal age ranging from ～4.3 Ma to ～7.0 Ma. The thickness of the sections varies significantly, depending perhaps on the development of local geomorphological conditions and the drainage system. Although the stratigraphy of the red clay sections has been recorded in some detail, correlation of the red clay sequences has not yet been undertaken. Geological records (Sun J. et al., 1998) have shown that during glacial periods of the Quaternary the deserts in northem China were greatly expanded compared with modern desert distribution. During interglacial periods, desert areas contracted and retreated mostly to northwestern China because of the increase in inland penetration of monsoonal precipitation. According to pedogenic characteristics of the red clay deposits, the climatic conditions of the Loess Plateau is warmer and wetter generally in the Neogene than in the late Pleistocene. Panicle analyses show that grain size distribution of the red clay sequence is similar to that of the paleosols in the Pleistocene loess record, thus implying a relatively remote provenance of the red clay materials. However, the quantitative or semiquantitative estimates of the distance from the source region to the Loess Plateau during the red clay development remains to be investigated. In this study, magnetostratigraphic and sedimentological studies are conducted at two thick red clay sequences-Jingchuan and Lingtai section. The objectives of these studies are focused on further sedimentological evidence for the eolian origin of the red clay, correlation of red clay sequences, provenance of the red clay, and the palaeoclimate reconstruction in the Neogene. Paleomagnetic studies show that the Jingchuan red clay has a basal age of 8.0 Ma, which is 1 million years older than the previously studied Lingtai section. The Lingtai red clay sequence was divided into five units on the basis of pedogenica characteristics (Ding et al., 1999a). The Jingchuan red clay sequence, however, can be lithologically divided into six units according to field observations. The upper five units of the Jingchuan red clay can generally correlate well with the five units of the Lingtai red clay. Comparison of magnetic susceptibility and color reflectance records of four red clay sections suggests that the Lingtai red clay sequence can be the type-section of the Neogene red clay deposits in northern China. Pleistocene loess and modem dust deposits have a unimodal grain-size distribution. The red clay sediments at Jingchuan and Lingtai also have a unimodal grain-size distribution especially similar to the paleosols in the Pleistocene loess record. Sedimentological studies of a north-south transect of loess deposits above S2 on the Loess Plateau show that loess deposits had distinct temporal and spatial sedimentary differentiation. The characteristics of such sedimentary differentiation can be well presented in a triangular diagram of normalized median grain size, normalized skewness, and normalized kurtosis. The triangular diagrams of the red clay-loess sequence at Lingtai and Jingchuan indicate that loess-paleosol-red clay may be transported and sorted by the same agent wind, thus extending the eolian record in the Loess Plateau from 2.6 Ma back to about 8.0 Ma. It has been recognized that during the last glacial maximum (LGM) the deserts in northern China had a distribution similar to the present, whereas during the Holocene Optimum the deserts retreated to the area west of the Helan Mountains. Advance-retreat cycles of the deserts will lead to changes in the distance of the Loess Plateau to the dust source regions, thereby controlling changes in grain size of the loess deposited in a specific site. To observe spatial changes in sedimentological characteristics of loess during the last glacial-interglacial cycle, the texture of loess was measured along the north-south transect of the Loess Plateau. Since the southern margin of the Mu Us desert during the LGM is already known, several models of grain size parameters versus the minimum distance from the source region to depositional areas were developed. According to these semiquantitative models, the minimum distance from the source region to Lingtai and Jingchuan areas is about 600 km during the Neogene. Therefore the estimated provenance of the Tertiary red clay deposits is the areas now occupied by the Badain Jaran desert and arid regions west of it. The ratio of the free iron to total iron concentration attests to being a good proxy indicator for the summer monsoon evolution. The Lingtai Fe_20_3 ratio record shows high values over three time intervals: 4.8-4.1 Ma, 3.4-2.6 Ma, and during the interglacial periods of the past 0.5 Ma. The increase in summer monsoon intensity over the three intervals also coincides with the well-developed soil characteristics. It is therefore concluded that the East-Asia summer monsoon has experienced a non-linear evolution since the late Miocene. In general, the East Asia summer monsoon was stronger in Neogene than in Quaternary and the strongest East Asia summer monsoon may occur between 4.1 and 4.8 Ma. The relatively small ice volume and high global temperature may be responsible for the strong summer monsoon during the early Pliocene.