Neuronal differentiation of human mesenchymal stem cells: changes in the expression of the Alzheimer's disease-related gene seladin-1

Seladin-1 (SELective Alzheimer's Disease INdicator-1) is an anti-apoptotic gene, which is down-regulated in brain regions affected by Alzheimer's disease (AD). In addition, seladin-1 catalyzes the conversion of desmosterol into cholesterol. Disruption of cholesterol homeostasis in neurons may increase cell susceptibility to toxic agents. Because the hippocampus and the subventricular zone, which are affected in AD, are the unique regions containing stem cells with neurogenic potential in the adult brain, it might be hypothesized that this multipotent cell compartment is the predominant source of seladin-1 in normal brain. In the present study, we isolated and characterized human mesenchymal stem cells (hMSC) as a model of cells with the ability to differentiate into neurons. hMSC were then differentiated toward a neuronal phenotype (hMSC-n). These cells were thoroughly characterized and proved to be neurons, as assessed by molecular and electrophysiological evaluation. Seladin-1 expression was determined and found to be significantly reduced in hMSC-n compared to undifferentiated cells. Accordingly, the total content of cholesterol was decreased after differentiation. These original results demonstrate for the first time that seladin-1 is abundantly expressed by stem cells and appear to suggest that reduced expression in AD might be due to an altered pool of multipotent cells.     

CD97 neutralisation increases resistance to collagen-induced arthritis in mice

Synovial tissue of rheumatoid arthritis (RA) patients is characterised by an influx and retention of CD97-positive inflammatory cells. The ligands of CD97, CD55, chondroitin sulfate B, and α5β1 (very late antigen [VLA]-5) are expressed abundantly in the synovial tissue predominantly on fibroblast-like synoviocytes, endothelium, and extracellular matrix. Based upon this expression pattern, we hypothesise CD97 expression to result in accumulation of inflammatory cells in the synovial tissue of RA patients. To determine the therapeutic effect of blocking CD97 in an animal model of RA, collagen-induced arthritis was induced in a total of 124 DBA/J1 mice. Treatment was started on day 21 (early disease) or on day 35 (longstanding disease) with the blocking hamster anti-mouse CD97 monoclonal antibody (mAb) 1B2, control hamster immunoglobulin, or NaCl, applied intraperitoneally three times a week. The paws were evaluated for clinical signs of arthritis and, in addition, examined by radiological and histological analysis. Mice receiving 0.5 mg CD97 mAb starting from day 21 had significantly less arthritis activity and hind paw swelling. Furthermore, joint damage and inflammation were reduced and granulocyte infiltration was decreased. When treatment was started on day 35, CD97 mAb treatment had similar effects, albeit less pronounced. The results support the notion that CD97 contributes to synovial inflammation and joint destruction in arthritis.     

The impact of drought spells on forests depends on site conditions: The case of 2017 summer heat wave in southern Europe

A major component of climate change is an increase in temperature and precipitation variability. Over the last few decades, an increase in the frequency of extremely warm temperatures and drought severity has been observed across Europe. These warmer and drier conditions may reduce productivity and trigger compositional shifts in forest communities. However, we still lack a robust, biogeographical characterization of the negative impacts of climate extremes, such as droughts on forests. In this context, we investigated the impact of the 2017 summer drought on European forests. The normalized difference vegetation index (NDVI) was used as a proxy of forest productivity and was related to the standardized precipitation evapotranspiration index, which accounts for the temperature effects of the climate water balance. The spatial pattern of NDVI reduction in 2017 was largely driven by the extremely warm summer for parts of the central and eastern Mediterranean Basin (Italian and Balkan Peninsulas). The vulnerability to the 2017 summer drought was heterogeneously distributed over Europe, and topographic factors buffered some of the negative impacts. Mediterranean forests dominated by oak species were the most negatively impacted, whereas Pinus pinaster was the most resilient species. The impact of drought on the NDVI decreased at high elevations and mainly on east and north‐east facing slopes. We illustrate how an adequate characterization of the coupling between climate conditions and forest productivity (NDVI) allows the determination of the most vulnerable areas to drought. This approach could be widely used for other extreme climate events and when considering other spatially resolved proxies of forest growth and health.     

A 450 million years long latitudinal gradient in age‐dependent extinction

Leigh Van Valen famously stated that under constant conditions extinction probability is independent of species age. To test this 'law of constant extinction', we developed a new method using deep learning to infer age‐dependent extinction and analysed 450 myr of marine life across 21 invertebrate clades. We show that extinction rate significantly decreases with age in > 90% of the cases, indicating that most species died out soon after their appearance while those which survived experienced ever decreasing extinction risk. This age‐dependent extinction pattern is stronger towards the Equator and holds true when the potential effects of mass extinctions and taxonomic inflation are accounted for. These results suggest that the effect of biological interactions on age‐dependent extinction rate is more intense towards the tropics. We propose that the latitudinal diversity gradient and selection at the species level account for this exceptional, yet little recognised, macroevolutionary and macroecological pattern.     

Gene expression profiling of early intervertebral disc degeneration reveals a down-regulation of canonical Wnt signaling and caveolin-1 expression: implications for development of regenerative strategies

Introduction

Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration.

Methods

Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age.

Results

Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells.

Conclusions

Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration.     

On the structure,typology and periodism of Cystoseira spinosa Sauvageau community and of Cystoseira zosteroides C. Agardh community from Eastern coast of Sicily (Mediterranean Sea)

Abstract

A study on Cystoseira spinosa community and Cystoseira zosteroides community from Catania (Eastern coast of Sicily) is presented. It is based on monthly samples carried out throughout a year. That permitted to better characterize the communities as regards their periodism and floristic composition. From the comparative examination of samples made, resulted that the communities differ each other mainly in the Cystoseira species since their floristic composition are on the whole quite similar.     

On three interesting marine red algae (Ceramiales,Rhodophyta) from the Mediterranean Sea

Abstract

Observations on three interesting Ceramiales from the Mediterranean Sea are reported; Ceramium incospicuum Zanardini, Polysiphonia setacea Hollenberg and Rodriguezella pinnata (Kützing) Schmitz ex Falkenberg. The male reproductive structures on the genus Rodriguezella are described for the first time.     

Intra-striatal estradiol in female rats impairs response learning within two hours of treatment

Estradiol treatment administered systemically or directly to the dorsolateral striatum across two days impairs performance on a response task in which rats learn to make a specific body turn to locate food on a maze. Estradiol can act through both slow and rapid signaling pathways to regulate learning impairments, however it is impossible to dissociate the slow from the rapid contributions of estradiol following long exposures. To assess the rapid effects of estradiol on striatum-sensitive learning, we trained rats on a response learning task after either relatively short or long treatments of estradiol infused directly into the striatum. Three-month-old female rats were ovariectomized 21 days before training and received guide cannulae implanted bilaterally into the dorsolateral striatum. For short duration treatments, rats were given bilateral infusions (0.5 μl) of 17β-estradiol-sulfate (0, 5, 50, or 500 nM in aCSF-vehicle) either 2 h or 15 min prior to training. For long duration treatments, rats received a series of estradiol infusions (500 nM) at 48, 24, and 2 h prior to training. Replicating previous findings (Zurkovsky et al., 2007), intra-striatal estradiol treatments given for two days prior to training impaired response learning. Estradiol-induced impairments in performance were also demonstrated 2 h, but not 15 min, after single infusions. Thus, estradiol acts within hours of exposure in the striatum, a structure lacking classical estrogen receptors, to impair response learning.     

Colonization,stability, and adaptation in a transplant experiment of the polymorphic land snail Cepaea nemoralis (Gastropoda: Pulmonata) at the edge of its geographical range

At the eastern margins of the geographical distribution in Europe, populations of Cepaea nemoralis are sparse and limited to urban environments to which they are possibly confined by relatively warmer climates. In 1999 we introduced 1101 C. nemoralis individuals originating from nine urban populations to a rural location in the area. The snails established a viable population, which suggests that confinement to urban settings is dispersal‐ rather than climate‐limited. The snails filled available habitats at a rate of approximately 400–600 m² year^?1. On the whole, morph frequencies remained remarkably stable; changes that occurred are attributable to segregation of alleles or chromosomes. However, snails responded to habitat heterogeneity: consistent and predictable divergence occurred between habitat types, such that light‐shelled snails were repeatedly more frequent in the open than in adjoining shaded habitats. This suggests the operation of climatic and/or visual selection. As the whole area encompassing seven distinct habitat patches was only 0.3 ha, and the maximum duration of population divergence was only 11 years (fewer than four snail generations), these results indicate extremely small temporal and spatial scales of adaptation during initial phases of population establishment and spread. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104 , 462–470.