Search

This work presents new information on the morphological aspects, reproductive biology and diet of the marbled electric ray Torpedo marmorata Risso 1810, in the Eastern Ionian and the Aegean Seas, from October 2017 to August 2020. The whole dataset consisted of 135 females and 109 males, ranging between 91–464 mm and 99–313 mm in total length (TL), respectively. The weight–length relationship of the species and the length frequency distribution of the sexes were described, corroborating the sexual dimorphism of the species. Thirty-one measurements were recorded to test the allometric growth of several characters for female and male specimens, whereas additional metrics (four) were used to investigate its reproductive cycle, in the north-eastern Mediterranean Sea. Sex ratio analysis was not significantly different from the 1:1 ratio. The size at which 50% of the species attained sexual maturity (L50) was the lowest recorded within the Mediterranean Sea for both sexes (261 mm for females and 241 mm for males). Mature males occurred throughout the year, whilst mature females (capable to reproduce) were present in spring and early autumn. The number of embryos ranged from five to 13 per brood. Stomach content examination revealed a preference of T. marmorata for fishes, with differences in prey item consumption between the Ionian and the Aegean Sea. This is the first attempt to describe the life-history traits of T. marmorata in the Greek Seas that will contribute to the future conservation status of the species.

Seagrass meadows and mussel reefs provide favorable habitats for many fish species, but few studies have compared the associated fish assemblages directly and examined the influence of environmental variables. Knowledge of fish assemblages associated with disparate habitats is needed for the conservation of coastal fisheries and marine spatial planning. Catch per unit effort data derived from fyke nets showed similar species richness and diversity in seagrass meadows and mussel reefs, suggesting that both habitats support elevated marine biodiversity of mobile fauna. However, it was shown that fish assemblage structure differed between those habitats, and also fish abundance in seagrass meadows was significantly higher than in mussel reefs by comparing the data with a multivariate extension of Generalized Linear Models (GLM). Furthermore, employing underwater video recordings to compare fish abundances in high and low water current speed mussel reefs with a Generalized Linear Mixed Model with negative binomial distribution, data revealed similar fish abundances (in terms of the MaxN metric) despite the variation in current speed, probably because the mussel formations provide sufficient shelter, even from high water currents. The commercially important species Atlantic cod (G. morhua), however, was significantly more abundant in the low water current mussel reef. Therefore, restoration efforts targeting G. morhua could benefit from restoring low current mussel reefs. Our study provides input for the conservation of coastal recreational and commercial fisheries, habitat restoration and marine spatial planning where certain habitats may be prioritized.

Stocks with low market value are rarely included in stock assessments because their catch records are generally lacking, thus adding to the already large number of un-assessed fisheries at a global scale. T his deficiency is more evident in the Mediterranean Sea where stock assessments are relatively fewer. A new method (AMSY) has been recently developed to assess stocks for which only abundance trends from scientific surveys are available. The AMSY method was used in the Aegean Sea to assess the status of 74 fish and invertebrate stocks (50 actinopterygians, 4 sharks, 5 rays, 12 cephalopods, and 3 crustaceans) for which catch data are lacking; 20 of them have medium or high market value and are being targeted by fishing fleets, while the remaining 54 are either not targeted, but by-caught and often discarded, or are not exploited at all. Overall, 31 of the 54 non-targeted stocks (57%) were healthy in terms of biomass (B/Bmsy > 1), whereas only 6 of the 20 targeted stocks (30%) were healthy. Of the 23 unhealthy non-targeted stocks, 12 were near healthy (B/Bmsy > 0.75), compared to only 1 of the targeted stocks, whereas 10 non-targeted stocks (19%) and 10 targeted ones (50%) were outside safe biological limits (B < 0.5Bmsy). Cephalopods and crustaceans were generally in a better status compared to fishes. The results confirm that fishing does not only affect commercial stocks, but it may also affect by-catch stocks. In general, stocks that are targeted by fishing fleets are in a worse status in terms of biomass compared to those that are only occasionally collected as by-catch or those that inhabit environments that are not accessible to fishing fleets.

Objective— We investigated the association between the functional, epigenetic, and expressional profile of human adventitial progenitor cells (APCs) and therapeutic activity in a model of limb ischemia. Approach and Results— Antigenic and functional features were analyzed throughout passaging in 15 saphenous vein (SV)–derived APC lines, of which 10 from SV leftovers of coronary artery bypass graft surgery and 5 from varicose SV removal. Moreover, 5 SV-APC lines were transplanted (8×10 5 cells, IM) in mice with limb ischemia. Blood flow and capillary and arteriole density were correlated with functional characteristics and DNA methylation/expressional markers of transplanted cells. We report successful expansion of tested lines, which reached the therapeutic target of 30 to 50 million cells in ≈10 weeks. Typical antigenic profile, viability, and migratory and proangiogenic activities were conserved through passaging, with low levels of replicative senescence. In vivo, SV-APC transplantation improved blood flow recovery and revascularization of ischemic limbs. Whole genome screening showed an association between DNA methylation at the promoter or gene body level and microvascular density and to a lesser extent with blood flow recovery. Expressional studies highlighted the implication of an angiogenic network centered on the vascular endothelial growth factor receptor as a predictor of microvascular outcomes. FLT-1 gene silencing in SV-APCs remarkably reduced their ability to form tubes in vitro and support tube formation by human umbilical vein endothelial cells, thus confirming the importance of this signaling in SV-APC angiogenic function. Conclusions— DNA methylation landscape illustrates different therapeutic activities of human APCs. Epigenetic screening may help identify determinants of therapeutic vasculogenesis in ischemic disease.

Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supramaximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into glioblastoma growth dynamics, with implications for understanding and limiting treatment resistance. Cancer Res; 75(1); 194–202. ©2014 AACR.

In this paper we developed a general stage-structured, Leslie-type model, suitable to simulate dynamics of soil arthropods under typical Mediterranean conditions. In order to explore arthropods’ life-history strategies in relation to enhanced spatial heterogeneity of the Mediterranean ecosystems, metapopulation characteristics were considered and different habitat quality regimes, in terms of dominant microclimatic conditions, were taken into account. Environmental stochasticity in temperature and humidity was incorporated into the model, and an elasticity analysis was conducted to quantify contribution of different life-history traits to metapopulation growth rate. The application of the model revealed well-known life-cycle characteristics of Mediterranean arthropods, such as seasonally fluctuating population sizes and skewing phenologies, a fact that confirms models’ reliability. Furthermore, the model seems able to elucidate controversial points of the animals’ life-cycle development, such as the long-term maintenance of populations in the field and the underlying mechanisms related to the adjustment to the specific features of the Mediterranean ecosystem. Subpopulations inhabiting various microsites display different dynamics and the interaction between these subpopulations, via dispersion, seems to be able to ensure stochastic equilibrium for the system. Dispersal appears to play a decisive role, allowing arthropods to conform to spatial severities and habitats fragmentation, rescuing individuals and recolonizing previously extinct habitats.

The aim of this study was to investigate a possible association between Helicobacter pylori infection and acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Of 17 consecutive patients with Guillain-Barre syndrome (GBS), 13 patients (six females; mean age 50 +/- 24 years) with AIDP were investigated. Clinical status was evaluated according to Hughes' score, and electrophysiological tests were performed within 2 weeks from disease onset. Helicobacter pylori infection was detected histologically and serum H. pylori-specific IgG antibodies were analysed by ELISA. Twenty asymptomatic patients (12 females; mean age 63 +/- 8 years), undergoing upper gastrointestinal endoscopy for investigation of mild iron deficiency anaemia, served as controls. Helicobacter pylori was found in 12 of 13 AIDP patients (92%), and in 10 of 20 controls (50%), (P = 0.02). Electrophysiological studies showed demyelination in all AIDP patients. High levels of anti-H. pylori IgG antibodies correlated with advanced clinical status. Five of seven AIDP patients with high levels of anti-H. pylori IgG antibodies had delayed F-wave latencies, indicating affection of proximal segments of peripheral nerves. Helicobacter pylori infection seems to be more frequent in AIDP patients. Anti-H. pylori titre might reflect advanced clinical status. Anti-H. pylori IgG antibodies are also associated with involvement of the proximal parts of peripheral nerves in AIDP.

INTRODUCTION: Glioblastoma (GB) is the most common and aggressive primary brain malignancy. Combining fluorescence-guided resection and neuroanatomy, we have identified three distinct compartments: the sub-ependymal zone (SEZ), the tumour mass (T) and the tumour margin (M). METHOD: RNA from T, SEZ and M of 15 GB patients was extracted for gene expression analysis using Trizol and cleaned up using Qiagen MiniElute columns prior to hybridization onto Illumina HT12v4 arrays. To assess whether genes in SEZ, T and M were differentially expressed, we performed analysis of variance (ANOVA)-type hypothesis testing. Genecodis was used to perform pathway analysis. RESULTS: We first investigated whether gene expression levels differed across SEZ, T and M where the M data represents tumour/host interface and identified the genes that were differentially expressed between SEZ-M and T-M (1449 and 2620 genes, respectively). Each list was functionally annotated to identify significant dysregulated pathways. SEZ-specific pathways were related to the immune response, while T-specific pathways were enriched in DNA repair and RNA metabolism. We focused our analysis on five key signaling cascades (Neurotrophin, MAPK, ErbB, Wnt, GnRH), which were dysregulated in both SEZ and T. The signaling cascade was more complex in T than in SEZ, although c-Myc was a central node to both networks. CONCLUSION: Transcriptional profiling of human GB compartments has identified groups of genes involved in critical molecular and cellular events that affect proliferation, survival, migration and differentiation. The gene expression study of each compartment may additionally contribute to our understanding of the genetic intra-tumour heterogeneity in GB.

BACKGROUND: Glioblastoma (GB) is the most common and aggressive primary brain malignancy. The disease is advanced at the time of clinical presentation and response to treatment may be confounded by clonal heterogeneity and differential patterns of resistance in spatially distinct parts of the same tumor. However, we do not understand how this complex environment evolves. Accumulating evidence suggests that intra-tumor heterogeneity is likely to be the key to understanding treatment failure, however the dynamics of such heterogeneity are still poorly understood. METHODS: Using a Fluorescence-Guided Multiple Sampling technique we obtained samples from the tumor mass, the sub-ependymal zone and the non-fluorescent tumor margin. We performed an integrated genomic analysis and combined copy number alteration and molecular clock data to develop a phylogenetic and spatial reconstruction of tumor evolution in individual patients. RESULTS: Phylogenetic reconstruction of the fragments from each GB identifies copy number alterations in EGFR and CDKN2A/B/p14ARF as early evolutionary events while aberrations in PDGFRA and PTEN occur later in the disease progression. Transcriptional profiling reveals that many patients display multiple GB subtypes within their tumor while deconstruction of the clonal organization of each tumor fragment at single-molecule level identified multiple coexisting cell lineages. Ancestral tumor precursors that gave rise to the tumor mass were found in the sub-ependymal zone of a subset of GB patients. However, in two patients the disease evolved from ancestors that were spatially remote from the sub-ependymal zone. CONCLUSIONS: Our integrated genomic analysis reports the evolution of GB in individual patients across multiple spatial scales. Our data reveals early clonal diversification generating a genetically complex and highly evolved disease environment at clinical presentation. We propose that these fundamental patient-specific tumor evolutionary dynamics underlie clinical phenotypic heterogeneity and may have implications for the emergence of resistant disease. SECONDARY CATEGORY: Neuropathology & Tumor Biomarkers.

Previous studies have suggested that schizophrenia is associ-ated with a reduced risk of cancer. Genes that are involved in cell cycle regulation seem to have additional functions in post-mitotic neurons involved in neuronal migration and synaptic plasticity. MicroRNAs (miRNAs) play a dominant role in the regulation of gene expression in the central nervous system (CNS). Due to their involvement in a large number of CNS pathways, miRNAs pose as appealing molecules for further investigation, with potential diagnostic, prognostic and therapeutic value. In the present study, we investigated the potential association between cancer and schizophrenia in 2 patient sample groups. We analyzed a large number of miRNAs in a control group of 6 schizophrenic patients and a study group of 8 schizophrenic patients with a solid tumor. A comparison between the control and study groups showed that only miR-183 was differentially expressed. Specifically, a significant downregulation of miR-183 in the samples of the study group was observed. Although a larger sample size is required to validate this result for the general patient population, our findings provide a first indication that miR-183 may play a role in regulating the expression of other genes with onco-suppressor activity. Our results are in agreement with the theory that patients with schizophrenia may have a tumor suppressor gene or enhanced neuronal apoptotic activities. Further studies are required in order to shed light on the role of miRNAs and particularly, on the suppressive role of miR-183 in the neurobiological pathways involved in schizophrenia.

Glioblastoma (GB) is advanced at the time of clinical presentation and response to treatment may be confounded by clonal heterogeneity and differential patterns of resistance in spatially distinct parts of the same tumor. However, we do not understand how this complex environment evolves. Accumulating evidence suggests that intra-tumor heterogeneity is likely to be the key to understanding treatment failure, however the dynamics of such heterogeneity are still poorly understood. Using a Fluorescence-Guided Multiple Sampling technique we obtained samples from the tumor mass, the sub-ependymal zone and the non-fluorescent tumor margin. We performed an integrated genomic analysis to develop a spatial reconstruction of tumor evolution in individual patients. Temporal analysis was performed using patient-derived xenografts obtained by serial transplantation of tumor cells in immuno-suppressed mice. Phylogenetic reconstruction of the fragments from each GB identifies copy number alterations in EGFR and CDKN2A/B/p14ARF as early evolutionary events while aberrations in PDGFRA and PTEN occur later in the disease progression. Transcriptional profiling reveals that many patients display multiple GB subtypes within their tumor while deconstruction of the clonal organization of each tumor fragment at single-molecule level identified multiple coexisting cell lineages. Ancestral tumor precursors that gave rise to the tumor mass were found in the sub-ependymal zone of a subset of GB patients. When used in in vivo experiments, tumor cells show variable competitive capacity for disease propagation and further genetic diversification, suggesting that GB evolves through complex dynamics of sub-clonal fitness advantage and acquisitions of mutations and copy number alterations. Our integrated genomic analysis addresses the evolution of GB in individual patients across multiple spatial scales. Our data reveal early clonal diversification generating a genetically complex and highly evolved disease environment at clinical presentation. We propose that these fundamental patient-specific tumor evolutionary dynamics underlie clinical phenotypic heterogeneity and may have implications for the emergence of resistant disease. Citation Format: Simon Tavaré, Andrea Sottoriva, Sara Piccirillo, Inma Spiteri, Anestis Touloumis, John C. Marioni, Christina N. Curtis, Colin Watts. Understanding tumor heterogeneity in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA04.

BACKGROUND: Glioblastoma (GB) is the most common and aggressive primary brain malignancy. The disease is advanced at the time of clinical presentation and response to treatment may be confounded by clonal heterogeneity and differential patterns of resistance in spatially distinct parts of the same tumor. However, we do not understand how this complex environment evolves. Accumulating evidence suggests that intra-tumor heterogeneity is likely to be the key to understanding treatment failure, however the dynamics of such heterogeneity are still poorly understood. METHODS: Using a Fluorescence-Guided Multiple Sampling technique we obtained samples from the tumor mass, the sub-ependymal zone and the non-fluorescent tumor margin. We performed an integrated genomic analysis based on copy number alteration and molecular clock data to develop a phylogenetic and spatial reconstruction of tumor evolution in individual patients. Temporal analysis was performed using patient-derived xenografts obtained by serial transplantation of tumor cells in immunosuppressed mice. RESULTS: Phylogenetic reconstruction of the fragments from each GB identifies copy number alterations in EGFR and CDKN2A/B/p14ARF as early evolutionary events while aberrations in PDGFRA and PTEN occur later in the disease progression. Transcriptional profiling reveals that many patients display multiple GB subtypes within their tumor while deconstruction of the clonal organization of each tumor fragment at single-molecule level identified multiple coexisting cell lineages. Ancestral tumor precursors that gave rise to the tumor mass were found in the sub-ependymal zone of a subset of GB patients. When used in in vivo experiments, tumor cells show variable competitive capacity for disease propagation and further genetic diversification suggesting that GB evolves through complex dynamics of sub-clonal fitness advantage and acquisitions of mutations and copy number alterations. CONCLUSION: Our integrated genomic analysis reports the evolution of GB in individual patients across multiple spatial scales. Our data reveals early clonal diversification generating a genetically complex and highly evolved disease environment at clinical presentation. In serial transplant experiments, subclonal growth advantage results in genetic diversification that ultimately produces additional heterogeneity. We propose that these fundamental patient-specific tumor evolutionary dynamics underlie clinical phenotypic heterogeneity and may have implications for the emergence of resistant disease.

Glioblastoma (GB), the most common and aggressive adult brain tumor, is characterized by phenotypic diversity and ultimately treatment failure. Using fluorescence-guided sampling we integrated copy number aberration, gene expression and molecular clock data to show that the sub-ependymal zone (SEZ) contains precursor cells of the corresponding mass. The genetically distinct tumor margin contains non self-renewing cells that retain the potential to regenerate the tumor. Functional assays confirmed that SEZ and marginal disease were less clinically aggressive compared to the mass compartment in the same tumor. However, resistance to supra-maximal chemotherapy doses and differential patterns of drug response were observed between compartments. These data provide novel insights into the basis of clinical diversity, poor treatment response and emergence of resistant disease in GB patients. Citation Format: Sara Grazia Maria Piccirillo, Inma Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J. Price, Richard Heywood, Nicola-Jane Francis, Vincent P. Collins, Ashok R. Venkitaraman, Christina Curtis, John C. Marioni, Simon Tavare’, Colin Watts. The human sub-ependymal zone harbors glioblastoma precursors and represents a distinct therapeutic target. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5016. doi:10.1158/1538-7445.AM2013-5016

Golgi tendon organs and muscle spindles were identified in serial sections of the temporalis and masseter muscles of kitten and cats. In the kitten, the position of each receptor was plotted in three-dimensional reconstitutions of the muscles. Seventy-four spindles and twenty tendon organs were identified in the temporalis, all in the region of the insertion into the mandible. Thirty-four spindles and six organs were located at the origin of the masseter muscle. The receptors were in deep portions of both muscles. All tendon organs were found to form complexes with one or more spindles.