Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by increasing mitochondrial membrane potential and cellular oxidative stress

'Tissue' transglutaminase (tTG) selectively accumulates in cells undergoing apoptosis both in vivo and in vitro. Considering the central role played by mitochondria in apoptosis, we investigated the relationships existing amongst tTG expression, apoptosis and mitochondrial function. To this aim we studied the mechanisms of apoptosis in a neuronal cell line (SK-N-BE (2)) in which the tTG-expression was driven by a constitutive promoter. Furthermore, a tet-off inducible promoter was also used in 3T3 fibroblastic cells used as control. Both cell lines, when expressing tTG, appeared 'sensitized' to apoptosis. Strikingly, we found major differences in the morphological features of mitochondria among cell lines in the absence of apoptotic stimuli. In addition, these ultrastructural characteristics were associated with specific functional features: (i) constitutively hyperpolarized mitochondria and (ii) increased reactive oxygen intermediates production. Importantly, after mitochondrial-mediated apoptosis by staurosporine, a rapid loss of mitochondrial membrane potential was found in tTG cells only. Taken together, these results seem to suggest that, via hyperpolarization, tTG might act as a 'sensitizer' towards apoptotic stimuli specifically targeted to mitochondria. These results could also be of pathogenetic relevance for those diseases that are characterized by increased tTG and apoptotic rate together with impaired mitochondrial function, e.g. in some neurodegenerative disease.

The toxicity of hexanedione isomers in neural and astrocytic cell lines

The metabolite 2,5-hexanedione (HD) is the cause of neurotoxicity linked with chronic n-hexane exposure. Acute exposure to high levels of 2,5-HD, have also shown toxic effects in neuronal cells and non-neuronal cells. Isomers of 2,5-HD, 2,3- and 3,4-HD, added to foodstuffs, are reported to be non-toxic. The acute cytotoxic effects of 2,5-, 2,3- and 3,4-HD were evaluated in neural (NT2.N, SK-N-SH), astrocytic (CCF-STTG1) and non-neural (NT2.D1) cell lines. All the cell lines were highly resistant to 2,5-HD (34-426 mM) at 4-h exposure, although sensitivity was greatest with NT2.D1, then SK-N-SH, NT2.N and finally the CCF-STTG1 line. At 24-h exposure, cell vulnerability increased 5-10-fold. The NT2.D1 cells were again the most sensitive, followed by NT2.N, SK-N-SH and then the CCF-STTG1 cells. 2,3- and 3,4-HD (8-84 mM), were significantly more toxic towards all four cell lines compared with 2,5-HD, after 4-h exposure. After 24-h exposure there was a 12-fold increase in inhibition of MTT turnover in the SK-N-SH cells and a 4-fold increase in the CCF-STTG1 cells, compared with 2,5-HD exposure. 2,3- and 3,4-HD, were significantly less toxic to the NT2.N cells than the SK-N-SH cells after 24-h exposure to the compounds, demonstrating a differing toxin vulnerability between these neural and neuroblastoma cell lines. This study indicates that these non-neuronal and neuronal cells are acutely resistant to 2,5-HD cytotoxicity, whilst the previously unreported sensitivity of all four cell lines to the 2,3- and 3,4- isomers of HD to has been shown to be significantly greater than that of 2,5-HD. © 2006 Elsevier B.V. All rights reserved.

On strongly regular graphs with m2 = qm3 and m3 = qm2

2010 Mathematics Subject Classification: 05C50.

Human Synaptic Plasticity Gene Expression Profile and Dendritic Spine Density Changes in HIV-Infected Human CNS Cells: Role in HIV-Associated Neurocognitive Disorders (HAND)

HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT2 Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (≥3 fold) down-regulated and 5 genes were significantly (≥3 fold) up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1) was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of apoptosis in astrocytes may contribute to the severe neuropathogenesis in clade B infection.

Global compilation of benthic data sets I

Approaches to quantify the organic carbon accumulation on a global scale generally do not consider the small-scale variability of sedimentary and oceanographic boundary conditions along continental margins. In this study, we present a new approach to regionalize the total organic carbon (TOC) content in surface sediments (<5 cm sediment depth). It is based on a compilation of more than 5500 single measurements from various sources. Global TOC distribution was determined by the application of a combined qualitative and quantitative-geostatistical method. Overall, 33 benthic TOC-based provinces were defined and used to process the global distribution pattern of the TOC content in surface sediments in a 1°x1° grid resolution. Regional dependencies of data points within each single province are expressed by modeled semi-variograms. Measured and estimated TOC values show good correlation, emphasizing the reasonable applicability of the method. The accumulation of organic carbon in marine surface sediments is a key parameter in the control of mineralization processes and the material exchange between the sediment and the ocean water. Our approach will help to improve global budgets of nutrient and carbon cycles.

Stable isotopes and Mg/Ca ratios on foraminifera and Ba/Ca ratios of sediment core SK168/GC-1

The past variability of the South Asian Monsoon is mostly known from records of wind strength over the Arabian Sea while high-resolution paleorecords from regions of strong monsoon precipitation are still lacking. Here, we present records of past monsoon variability obtained from sediment core SK 168/GC-1, which was collected at the Alcock Seamount complex in the Andaman Sea. We utilize the ecological habitats of different planktic foraminiferal species to reconstruct freshwater-induced stratification based on paired Mg/Ca and d18O analyses and to estimate seawater d18O (d18Osw). The difference between surface and thermocline temperatures (delta T) and d18Osw (delta d18Osw) is used to investigate changes in upper ocean stratification. Additionally, Ba/Ca in G. sacculifer tests is used as a direct proxy for riverine runoff and sea surface salinity (SSS) changes related to monsoon precipitation on land. Our delta d18Osw time series reveals that upper ocean salinity stratification did not change significantly throughout the last glacial suggesting little influence of NH insolation changes. The strongest increase in temperature gradients between the mixed layer and the thermocline is recorded for the mid-Holocene and indicate the presence of a significantly shallower thermocline. In line with previous work, the d18Osw and Ba/Ca records demonstrate that monsoon climate during the LGM was characterized by a significantly weaker southwest monsoon circulation and strongly reduced runoff. Based on our data the South Asian Summer Monsoon (SAM) over the Irrawaddyy strengthened gradually after the LGM beginning at ~18 ka. This is some 3 kyrs before an increase of the Ba/Ca record from the Arabian Sea and indicates that South Asian Monsoon climate dynamics are more complex than the simple N-S displacement of the ITCZ as generally described for other regions. Minimum d18Osw values recorded during the mid-Holocene are in phase with Ba/Ca marking a stronger monsoon precipitation, which is consistent with model simulations.

Comparison of radiobiological effects induced by ultra-high and standard dose rate of x-rays on a radio-resistant cell line

Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a ultra-high dose rate comparing them with standard dose rate. In this regard, a radioresistant SK-MEL-28 cell line were irradiated with x-ray in order to have a total dose of 2 and 4 Gy, at two different dose rate. The ultra-high dose rate is a specific property of the dense plasma focus (DPF) device, which has pulsed operation and thus gives short and highly energetic pulses of multiple types of rays and particles, in this case, we focused our study on the influence of X-rays. While a low dose rate is obtained with conventional X-ray tube. In this study it results that a ultra-high dose rate enhances radiosensitivity of melanoma cells while reducing the adhesion, proliferation and migration ability of cells.

Tracer-based assessment of flow paths, storage and runoff generation in northern catchments : a review

Peer reviewed

Low frequency of cigarette smoking and the risk of head and neck cancer in the INHANCE consortium pooled analysis

Funding • The pooled data coordination team (PBoffetta, MH, YCAL) were supported by National Cancer Institute grant R03CA113157 and by National Institute of Dental and Craniofacial Research grant R03DE016611 • The Milan study (CLV) was supported by the Italian Association for Research on Cancer (Grant no. 10068). • The Aviano study (LDM) was supported by a grant from the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research • The Italy Multicenter study (DS) was supported by the Italian Association for Research on Cancer (AIRC), Italian League Against Cancer and Italian Ministry of Research. • The Study from Switzerland (FL) was supported by the Swiss League against Cancer and the Swiss Research against Cancer/Oncosuisse [KFS-700, OCS-1633]. • The central Europe study (PBoffetta, PBrenan, EF, JL, DM, PR, OS, NS-D) was supported by the World Cancer Research Fund and the European Commission INCOCOPERNICUS Program [Contract No. IC15- CT98-0332] • The New York multicentre study (JM) was supported by a grant from National Institute of Health [P01CA068384 K07CA104231]. • The study from the Fred Hutchison Cancer Research Center from Seattle (CC, SMS) was supported by a National Institute of Health grant [R01CA048996, R01DE012609]. • The Iowa study (ES) was supported by National Instituteof Health [NIDCR R01DE011979, NIDCR R01DE013110, FIRCA TW001500] and Veterans Affairs Merit Review Funds. • The North Carolina studies (AFO) were supported by National Institute of Health [R01CA061188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]. • The Tampa study (PLazarus, JM) was supported by National Institute of Health grants [P01CA068384, K07CA104231, R01DE013158] • The Los Angeles study (Z-F Z, HM) was supported by grants from National Institute of Health [P50CA090388, R01DA011386, R03CA077954, T32CA009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center. • The Houston study (EMS, GL) was supported by a grant from National Institute of Health [R01ES011740, R01CA100264]. • The Puerto Rico study (RBH, MPP) was supported by a grant from National Institutes of Health (NCI) US and NIDCR intramural programs. • The Latin America study (PBoffetta, PBrenan, MV, LF, MPC, AM, AWD, SK, VW-F) was supported by Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a‘ Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222] • The IARC multicentre study (SF, RH, XC) was supported by Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/ 0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant. • The Boston study (KKelsey, MMcC) was supported by a grant from National Institute of Health [R01CA078609, R01CA100679]. • The Rome study (SB, GC) was supported by AIRC (Italian Agency for Research on Cancer). • The US multicentre study (BW) was supported by The Intramural Program of the National Cancer Institute, National Institute of Health, United States. • The Sao Paolo study (V W-F) was supported by Fundacao de Ampara a Pesquisa no Estado de Sao Paulo (FAPESP No 10/51168-0) • The MSKCC study (SS, G-P Y) was supported by a grant from National Institute of Health [R01CA051845]. • The Seattle-Leo stud (FV) was supported by a grant from National Institute of Health [R01CA030022] • The western Europe Study (PBoffetta, IH, WA, PLagiou, DS, LS, FM, CH, KKjaerheim, DC, TMc, PT, AA, AZ) was supported by European Community (5th Frame work Programme) grant no QLK1-CT-2001- 00182. • The Germany Heidelberg study (HR) was supported by the grant No. 01GB9702/3 from the German Ministry of Education and Research.

Targeting androgen receptor activation function-1 with EPI to overcome resistance mechanisms in castration-resistant prostate cancer

Financial support: This research was supported by grants to MDS from the NCI (2R01CA105304), the Canadian Institutes of Health Research (MOP79308) and the US Army Medical Research and Materiel Command Prostate Cancer Research Program (E81XWH-11-1-0551). Research by IJM’s group was supported by the Chief Scientist’s Office of the Scottish Government (ETM-258 and -382). We are grateful to Country Meadows Senior Men’s Golf Charity Classic for financial support of this research.

See-saw relationship of the Holocene East Asian-Australian summer monsoon

D.E. and N.M. acknowledge support by the Leibniz Association (WGL) under Grant No. SAW-2013-IZW-2. F.H.M.’s research is funded through an Australian Postgraduate Award. I.O. is financially supported from TUBITAK under 2214/A program and by Ege University under the Research Project number 2015FEN028. This study received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie grant agreement No 691037. The publication of this article was funded by the Open Access Fund of the Leibniz Association. K.H.W. thank Rhawn F. Denniston for his wider involvement in the northwest Australian monsoon project and the Kimberley Foundation Australia for financial support for this project and Paul Wyrwoll for helpful comments. We are also grateful to Yanjun Cai for providing the Lake Qinghai record.

Projected responses of North American grassland songbirds to climate change and habitat availability at their northern range limits in Alberta, Canada

Across North America, grassland songbirds have undergone steep population declines over recent decades, commonly attributed to agricultural intensification. Understanding the potential interactions between the impacts of climate change on the future distributions of these species and the availability of suitable vegetation for nesting can support improved risk assessments and conservation planning for this group of species. We used North American bioclimatic niche models to examine future changes in suitable breeding climate for 15 grassland songbird species at their current northern range limits along the boreal forest–prairie ecotone in Alberta, Canada. Our climate suitability projections, combined with the current distribution of native and tame pasture and cropland in Alberta, suggest that some climate-mediated range expansion of grassland songbirds in Alberta is possible. For six of the eight species projected to experience expansions of suitable climate area in Alberta, this suitable climate partly overlaps the current distribution of suitable land cover. Additionally, for more than half of the species examined, most of the area of currently suitable climate was projected to remain suitable to the end of the century, highlighting the importance of Alberta for the long-term persistence of these species. Some northern prairie-endemic species exhibited substantial projected northward shifts of both the northern and southern edges of the area of suitable climate. Baird’s Sparrow (Ammodramus bairdii) and Sprague’s Pipit (Anthus spragueii), both at-risk grassland specialists, are predicted to have limited climate stability within their current ranges, and their expansion into new areas of suitable climate may be limited by the availability of suitable land cover. Our results highlight the importance of the preservation and restoration of remaining suitable grassland habitat within areas of projected climate stability and beyond current northern range limits for the long-term persistence of many grassland songbird species in the face of climate change.

Refractometer probe based on a reflective carbon nanotube-modified microfiber Bragg grating

A carbon nanotube (CNT)-modified microfiber Bragg grating (MFBG) is proposed to measure the refractive index with a strong enhancement of the sensitivity in the low refractive index region. The introduction of the CNT layer influences the evanescent field of the MFBG and causes modification of the reflection spectrum. With the increase of the surrounding refractive index (SRI), we observe significant attenuation to the peak of the Bragg resonance, while its wavelength remains almost unchanged. Our detailed experimental results disclose that the CNT-MFBG demonstrates strong sensitivity in the low refractive index range of 1.333-1.435, with peak intensity up to -53.4 dBm/refractive index unit, which is 15-folds higher than that of the uncoated MFBG. Therefore, taking advantage of the CNT-induced evanescent field enhancement, the reflective MFBG probe presents strong sensing capability in biochemical fields.