Cell death,gliosis, and synaptic remodeling in the hippocampus of epileptic rats

Seizures set in motion complex molecular and morphological changes in vulnerable structures, such as the hippocampal complex. A number of these changes are responsible for neuronal death of CA3 and hilar cells, which involves necrotic and apoptotic mechanisms. In surviving dentate granule cells seizures induce an increased expression of tubulin subunits and microtubule-associated proteins, suggesting that an overproduction of tubulin polymers would lead to a remodeling of mossy fibers (the axons of granule cells). In fact, these fibers sprout in the dentate gyrus to innervate granule cell dendrites, creating recurrent excitatory circuits. In contrast, terminal mossy fibers do not sprout in the CA3 field. Navigation of mossy fiber's growth cones may be facilitated by astrocytes, which would exert differential effects by producing and excreting cell adhesion and substrate molecules. In the light of the results discussed here, we suggest that in adult brain activated-resident astrocytes (nonproliferating, tenascin-negative, neuronal cell-adhesion molecule-positive astrocytes) could contribute to the process of axonal outgrowth and synaptogenesis in the dentate gyrus, while proliferating astrocytes, tenascin-positive, could impede any axonal rearrangement in CA3. © 1995 John Wiley & Sons, Inc.     

From Biodiversity to Ecodiversity: A Landscape-Ecology Approach to Conservation and Restoration

An environmental revolution is urgently needed that will lead to a post-industrial symbiosis between man and nature. This can be realized only if the present unrestrained biological impoverishment and neotechnological landscape degradation are replaced by the creation of healthy and attractive landscapes. Restorationists can fulfill a vital role in this process. They must broaden their scales from biodiversity restoration in small, protected nature islands to the large-scale restoration of natural and cultural landscapes. To achieve this they must restore not only the patterns of vegetation but also the processes that create these patterns, including human land uses. Their goal should be to restore the total biological, ecological, and cultural landscape diversity, or “ecodiversity,” and its intrinsic and instrumental values of highly valuable, endangered seminatural, agricultural and rural landscapes. For this purpose it is essential to maintain and restore the dynamic flow equilibrium between biodiversity, ecological, and cultural landscape heterogeneity, as influenced by human land uses, which occur at different spatial and temporal scales and intensities. Recent advances in landscape ecology should be utilized for broader assessment of ecodiversity, including proposed indices of ecodiversity, new techniques such as Intelligent Geographical Information Systems (IGIS), and Green Books for the holistic conservation and restoration of valuable endangered landscapes. Restoration ecology can make an important contribution to an urgently needed environmental revolution. This revolution should lead to a new symbiosis between man and nature by broadening the goal of vegetation restoration to ecological and cultural landscape restoration, and thereby to total landscape ecodiversity.     

Synthesis of tritiated 4,4′-diisothiocyano-2,2′-stilbene disulfonic acid ([3H]DIDS) and its covalent reaction with sites related to anion transport in human red blood cells

Summary The potent and specific inhibitor of anion permeability, 4,4-diisothicyanostilbene-2,2-disulfonic acid (DIDS) was synthesized in tritiated form ([³H]DIDS) from tritiated 5-nitrotoluene-o-sulfonic acid. Its reactions with and effects on red blood cells were compared with those of a reduced form ([³H]H₂DIDS), previously used as a tracer for DIDS. The rate of covalent reaction of [³H]DIDS was substantially faster than that of [³H]H₂DIDS at all temperatures tested. With both agents, the rate of reaction was increased in alkaline media, although the response occurred at a lower pH with [³H]DIDS. On the other hand, the relationship of irreversible membrane binding to the degree of inhibition of sulfate fluxes was linear and virtually the same for both agents, with 100% inhibition associated with the binding of approximately 1.2×10⁶ molecules per cell. About 90% of the binding for each probe was to a particular membrane protein, known as band 3, equivalent to about 1 mole of agent per mole of protein.     

Microsite differentiation in a Mediterranean oak savanna

Abstract. Microscale variation of vegetation was studied in a Mediterranean oak savanna dominated by annual plants at Neve Ya'ar Experimental Station, in the lower Galilee of Israel. Species presence/absence data were recorded in 20 cm x 20 cm quadrats on a 500-quadrat transect. These data were ordinated with Detrended Correspondence Analysis. Soil nitrate, phosphorous, potassium, pH, soil moisture and salinity were determined at 2-m intervals on the 100-m transect, at monthly intervals from November 1981 to April 1982. Litter cover and canopy shade were surveyed in October 1981 and April 1982. A sharp rise in available nitrate occurred in November, following the first winter rains. Patterns in herbaceous vegetation, as expressed by sample ordination scores, correlated best with litter cover in October. This suggested that vegetation pattern in this community may be strongly influenced by environmental conditions at the time of seedling germination and establishment.     

Incorporating physiology into species distribution models moderates the projected impact of warming on selected Mediterranean marine species

Species distribution models (SDMs) correlate species occurrences with environmental predictors, and can be used to forecast distributions under future climates. SDMs have been criticized for not explicitly including the physiological processes underlying the species response to the environment. Recently, new methods have been suggested to combine SDMs with physiological estimates of performance (physiology-SDMs). In this study, we compare SDM and physiology-SDM predictions for select marine species in the Mediterranean Sea, a region subjected to exceptionally rapid climate change. We focused on six species and created physiology-SDMs that incorporate physiological thermal performance curves from experimental data with species occurrence records. We then contrasted projections of SDMs and physiology-SDMs under future climate (year 2100) for the entire Mediterranean Sea, and particularly the ‘warm’ trailing edge in the Levant region. Across the Mediterranean, we found cross-validation model performance to be similar for regular SDMs and physiology-SDMs. However, we also show that for around half the species the physiology-SDMs substantially outperform regular SDM in the warm Levant. Moreover, for all species the uncertainty associated with the coefficients estimated from the physiology-SDMs were much lower than in the regular SDMs. Under future climate, we find that both SDMs and physiology-SDMs showed similar patterns, with species predicted to shift their distribution north-west in accordance with warming sea temperatures. However, for the physiology-SDMs predicted distributional changes are more moderate than those predicted by regular SDMs. We conclude, that while physiology-SDM predictions generally agree with the regular SDMs, incorporation of the physiological data led to less extreme range shift forecasts. The results suggest that climate-induced range shifts may be less drastic than previously predicted, and thus most species are unlikely to completely disappear with warming climate. Taken together, the findings emphasize that physiological experimental data can provide valuable supplemental information to predict range shifts of marine species.     

Tooth periodontal ligament: Direct 3D microCT visualization of the collagen network and how the network changes when the tooth is loaded

The periodontal ligament (PDL), a soft tissue connecting the tooth and the bone, is essential for tooth movement, bone remodeling and force dissipation. A collagenous network that connects the tooth root surface to the alveolar jaw bone is one of the major components of the PDL. The organization of the collagenous component and how it changes under load is still poorly understood. Here using a state-of-the-art custom-made loading apparatus and a humidified environment inside a microCT, we visualize the PDL collagenous network of a fresh rat molar in 3D at 1 μm voxel size without any fixation or contrasting agents. We demonstrate that the PDL collagen network is organized in sheets. The spaces between sheets vary thus creating dense and sparse networks. Upon vertical loading, the sheets in both networks are stretched into well aligned arrays. The sparse network is located mainly in areas which undergo compressive loading as the tooth moves towards the bone, whereas the dense network functions mostly in tension as the tooth moves further from the bone. This new visualization method can be used to study other non-mineralized or partially mineralized tissues, and in particular those that are subjected to mechanical loads. The method will also be valuable for characterizing diseased tissues, as well as better understanding the phenotypic expressions of genetic mutants.     

The Therapeutic Potential of AN-7, a Novel Histone Deacetylase Inhibitor,for Treatment of Mycosis Fungoides/Sezary Syndrome Alone or with Doxorubicin

The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H₃, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS.     

Cortical hypercolumn size determines stereo fusion limits

The size of a pair of cortical ocular dominance columns determines a basic anatomical module of V-1 which Hubel and Wiesel have termed the hypercolumn. Does this correspond to a basic functional, or psychophysically measurable, module as well? This is the basic question addressed in the present paper. Since the ocular dominance column architecture is presumed to be related to stereo vision, it is natural to assume that hypercolumn size should provide a modular basis for basic phenomena of stereopsis. In previous work, we have suggested that local nonlinear filtering via the cepstral transform, operating on a local window of cortical tissue scaled by hypercolumn size, provides such a modular model of stereopsis. In the present paper, we review this model and then discuss a number of issues related to the biological plausibility and implementation of this algorithm. Then, we present the main result of this paper: we have analyzed a number of experiments related to stereo fusion limits (Panum's area) and to disparity gradient and disparity scaling, and demonstrate that there is a simple unifying explanation for these phenomena in terms of a constant cortical module whose size is determined by a pair of ocular dominance columns. As a corollary, Panum's area must increase according to (inverse) cortical magnification factor. We show that this is supported by all existing experimental data.