Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration

Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant retinitis pigmentosa (RP). In P23H rats administered with HU210 (100 μg/kg, i.p.) from P24 to P90, ERG recordings showed an amelioration of vision loss, as compared to vehicle-administered animals. Under scotopic conditions, the maximum a-wave amplitudes recorded at P60 and P90 were higher in HU210-treated animals, as compared to the values obtained in untreated animals. The scotopic b-waves were significantly higher in treated animals than in untreated rats at P30, P60 and P90. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. HU210-treated animals had 40% more photoreceptors than untreated animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were also preserved in HU210-treated P23H rats. These results indicate that HU210 preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in P23H rats. These data suggest that cannabinoids are potentially useful to delay retinal degeneration in RP patients.

Phagocytosis of Photoreceptor Outer Segments by Transplanted Human Neural Stem Cells as a Neuroprotective Mechanism in Retinal Degeneration

Purpose. Transplantation of human central nervous system stem cells (HuCNS-SC) into the subretinal space of Royal College of Surgeons (RCS) rats preserves photoreceptors and visual function. To explore possible mechanism(s) of action underlying this neuroprotective effect, we performed a detailed morphologic and ultrastructure analysis of HuCNS-SC transplanted retinas. Methods. The HuCNS-SC were transplanted into the subretinal space of RCS rats. Histologic examination of the transplanted retinas was performed by light and electron microscopy. Areas of the retina adjacent to HuCNS-SC graft (treated regions) were analyzed and compared to control sections obtained from the same retina, but distant from the transplant site (untreated regions). Results. The HuCNS-SC were detected as a layer of STEM 121 immunopositive cells in the subretinal space. In treated regions, preserved photoreceptor nuclei, as well as inner and outer segments were identified readily. In contrast, classic signs of degeneration were observed in the untreated regions. Interestingly, detailed ultrastructure analysis revealed a striking preservation of the photoreceptor–bipolar–horizontal cell synaptic contacts in the outer plexiform layer (OPL) of treated areas, in stark contrast with untreated areas. Finally, the presence of phagosomes and vesicles exhibiting the lamellar structure of outer segments also was detected within the cytosol of HuCNS-SC, indicating that these cells have phagocytic capacity in vivo. Conclusions. This study reveals the novel finding that preservation of specialized synaptic contacts between photoreceptors and second order neurons, as well as phagocytosis of photoreceptor outer segments, are potential mechanism(s) of HuCNS-SC transplantation, mediating functional rescue in retinal degeneration.

Evaluating Taphonomic Bias in a Storm-Disturbed Carbonate Platform: Effects of Compositional and Environmental Factors in Lower Jurassic Brachiopod Accumulations (Eastern Subbetic Basin, Spain)

In order to evaluate taxonomic and environmental control on the preservation pattern of brachiopod accumulations, sedimentologic and taphonomic data have been integrated with those inferred from the structure of brachiopod accumulations from the easternmost Lower Jurassic Subbetic deposits in Spain. Two brachiopod communities (Praesphaeroidothyris and Securina communities) were distinguished showing a mainly free-lying way of life in soft-bottom habitats. Three taphofacies are discriminated based on proportion of disarticulation, fragmentation, packing, and shell filling. Taphofacies 1 is represented by thinly fragmented, dispersed brachiopod shells in wackestone beds. Taphofacies 2 is spatially restricted to small lenses where shells are poorly fragmented, rarely disarticulated, usually void filled, and highly packed. Taphofacies 3 is represented by mud or cement filled, loosely packed, articulated brachiopods forming large pocket-like structures. Temporal and spatial averaging were minimally involved in taphofacies 2 and 3. It is interpreted that patchy preservation implies preservation of primary original patchiness of brachiopod communities on the seafloor. The origin of shell-rich taphofacies (2 and 3) is related to rapid burial due to episodic storm activity, while shell-poor taphofacies 1 records background conditions. The nature and comparative diversity of these taphofacies underscores the importance of rapid burial for shell beds preservation. Differences in preservation between taphofacies 2 and 3 are mainly related to environmental criteria, most importantly storm energy and water depth. In contrast, the taxonomic-specific pattern of the communities is a subordinate element of control, controlling only minor within-taphofacies differences in preservation.

Stability in Linear Optimization Under Perturbations of the Left-Hand Side Coefficients

This paper studies stability properties of linear optimization problems with finitely many variables and an arbitrary number of constraints, when only left hand side coefficients can be perturbed. The coefficients of the constraints are assumed to be continuous functions with respect to an index which ranges on certain compact Hausdorff topological space, and these properties are preserved by the admissible perturbations. More in detail, the paper analyzes the continuity properties of the feasible set, the optimal set and the optimal value, as well as the preservation of desirable properties (boundedness, uniqueness) of the feasible and of the optimal sets, under sufficiently small perturbations.

Construction of 17-19th century domes in the province of Alicante (Spain): the case of San Juan Bautista in Cox

From the late seventeenth to early nineteenth centuries, many religious temples have been built in the province of Alicante (south east of Spain) with brick domes as their main characteristic feature. Often, the limited data available about these remarkable constructions make rehabilitation interventions become into real research projects, with a high value for their historic conservation over time. The aim of this paper is to show a detailed refurbishment analysis of a religious temple built in 1778, showing the need of preservation of historic buildings as a part of the architectural heritage by establishing a common pattern of materials, geometry and constructive systems, specifically in their domes. In most cases, there was not an architectural project for the construction, that is why the analysis of any documentary and archival sources available is essential to find different ways to proceed on the use and maintenance of these religious buildings.

Community dynamics of stabilized dune xerophytic shrubs

Tese de doutoramento, Biologia (Ecologia), Universidade de Lisboa, Faculdade de Ciências, 2016

'The power gained, we will never surrender': Russian ruling elite versus the succession and economic crisis. OSW Point of View (Policy Brief), October 2009

Even though the economic crisis proved harmful to the Russian economy and people's living standards, it has nonetheless failed to make the elite revise its policy. Despite some problems, the government has managed to sustain economic and political stability, thanks to the reserves it amassed in the times of prosperity, and to the propaganda campaign that protected it, above all Vladimir Putin. The crisis failed to force the elite to implement deeper structural and political reforms. Moreover, it has actually reinforced existing tendencies, such as state control over the economy and its oil-oriented character, the elite's economic expansion at the expense of private businesses, and the preservation of political power. Thus, the crisis has so far failed to dismantle Putinism, indeed quite the reverse - it has in fact contributed to its becoming 'set in stone'.

Estimated chronologic ages of benthic microfossil events in ODP Site 105-647 (Table 1)

Benthic foraminifers were examined from the Paleogene of Ocean Drilling Program (ODP) Site 647 and Deep Sea Drilling Program (DSDP) Site 112 in the southern Labrador Sea. The Paleogene sequence of the deep Labrador Sea can be subdivided into seven assemblages, based on the ranges and relative abundance of characteristic taxa. The first occurrences (FOs) and last occurrences (LOs) of important benthic taxa are calibrated to a standard biochronology, by interpolating from our age model for Site 647. The biostratigraphy of Site 647 is used to improve the age estimates of Site112 cores. Fifteen microfossil events in Site 647 also are found in the sedimentary wedge along the Labrador Margin. A comparison of the probabilistic microfossil sequence from the Labrador Margin with that at Site 647 yields four isochronous benthic foraminifer LOs. Two new species are described from Sites 647 and 112: Hyperammina kenmilleri, Kaminski n.sp., and Ammodiscus nagyi Kaminski n.sp. Significant faunal turnovers are observed at the Ypresian/Lutetian and Eocene/Oligocene boundaries. The Ypresian/Lutetian boundary is characterized by a Glomospira-facies and is attributed to a rise in the CCD (carbonate compensation depth) associated with the NP14 lowstand in sea level. The Eocene/Oligocene boundary is delimited by the LO of Spiroplectammina spectabilis and Reticulophragmium amplectens. The change from an Eocene agglutinated assemblageto a predominantly calcareous assemblage in the early Oligocene took place gradually, over a period of about 4 Ma, but the rate of change accelerated near the boundary. This faunal turnover is attributed to changes in the preservationof agglutinated foraminifers, as delicate species disappeared first. Increasingly poorer preservation of agglutinated foraminifers in the late Eocene to earliest Oligocene reflects the first appearance of cool, nutrient-poor deep water in the southern Labrador Sea. The approximately coeval disappearance of agglutinated assemblages along the Labrador Margin was caused by a regional trend from slope to shelf environments, accentuated by the 'mid'-Oligocene lowstand in sea level.

Organic petrology of Neogene sediment from ODP Leg 117

Neogene sediments from three areas of the Northern Indian Ocean (Indus Fan, Owen Ridge, Oman Margin, ODP Leg 117) were studied in order to determine the amount, type, and preservation of organic matter as functions of the environments encountered. The work consisted of geochemical analyses on whole sediment (Total Organic Content and Rock Eval pyrolysis) and of petrographic studies on isolated organic matter by optical and scanning electron microscopy. In Indus Fan sediments, organic matter is present in low amounts, mainly as lignaceous fragments. A contrasting situation exists in Oman Margin sediments which are generally rich in amorphous autochtonous organic matter. Owen Ridge, located between Indus fan and Oman Margin areas, shows two phases of organic sedimentation as a consequence of the uplift of the ridge. The older phase (Oligocene to early or middle Miocene) is strongly influenced by detrital supply from the Indus, while the younger phase (middle Miocene to Pleistocene) is characterized by relatively high amounts of autochtonous organic matter. From a general point of view it appears that high amounts of organic matter are mainly due to good preservation of marine amorphous organic matter, such as in Oman Margin sediments and in upper pelagic levels of Indus Fan and Owen Ridge deposits. Low total organic carbon contents are correlated with low proportions of amorphous material in the total organic matter due to oxidizing conditions. This leads to a relative enrichment in components derived from resistant materials (lignin, chitin, or other resistant biopolymers) such as lignaceous fragments (Indus Fan) and/or fragments from benthic organisms and alveolate microplankton (Oman Margin).

Calcareous nannofossil stratigraphy and datums of sediments from ODP Leg 198 sites

A relatively complete lower Paleocene to lower Oligocene sequence was recovered from the Southern High of Shatsky Rise at Sites 1209, 1210, and 1211. The sequence consists of nannofossil ooze and clay-rich nannofossil ooze. Samples from these sites have been the target of intensive calcareous nannofossil biostratigraphic investigations. Calcareous nannofossils are moderately preserved in most of the recovered sequence, which extends from nannofossil Zones CP1 to CP16. Most traditional zonal markers are present; however, the rarity and poor preservation of key species in the uppermost Paleocene and lower Eocene inhibits zonal subdivision of part of this sequence.