The present and future of serum diagnostic tests for testicular germ cell tumours.

Testicular germ cell tumours (GCTs) are the most common malignancy occurring in young adult men and the incidence of these tumours is increasing. Current research priorities in this field include improving overall survival for patients classified as being 'poor-risk' and reducing late effects of treatment for patients classified as 'good-risk'. Testicular GCTs are broadly classified into seminomas and nonseminomatous GCTs (NSGCTs). The conventional serum protein tumour markers α-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and lactate dehydrogenase (LDH) show some utility in the management of testicular malignant GCT. However, AFP and hCG display limited sensitivity and specificity, being indicative of yolk sac tumour (AFP) and choriocarcinoma or syncytiotrophoblast (hCG) subtypes. Furthermore, LDH is a very nonspecific biomarker. Consequently, seminomas and NSGCTs comprising a pure embryonal carcinoma subtype are generally negative for these conventional markers. As a result, novel universal biomarkers for testicular malignant GCTs are required. MicroRNAs are short, non-protein-coding RNAs that show much general promise as biomarkers. MicroRNAs from two 'clusters', miR-371-373 and miR-302-367, are overexpressed in all malignant GCTs, regardless of age (adult or paediatric), site (gonadal or extragonadal) and subtype (seminomas, yolk sac tumours or embryonal carcinomas). A panel of four circulating microRNAs from these two clusters (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p) is highly sensitive and specific for the diagnosis of malignant GCT, including seminoma and embryonal carcinoma. In the future, circulating microRNAs might be useful in diagnosis, disease monitoring and prognostication of malignant testicular GCTs, which might also reduce reliance on serial CT scanning. For translation into clinical practice, important practical considerations now need addressing.The authors would like to acknowledge grant funding from CwCUK/GOSHCC (M.J.M. N.C. grant W1058), SPARKS (M.J.M. N.C. grant 11CAM01), CRUK (N.C. grant A13080) MRC (M.J.M. grant MC_EX_G0800464) and National Health Service funding to the Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre for Cancer (R.A.H.). The authors also thank the Max Williamson Fund, the Josh Carrick Foundation and The Perse Preparatory School, Cambridge for support.This is the author accepted manuscript. The final version is available fromNature Publishing Group via https://doi.org/10.1038/nrurol.2016.17

A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries

The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo- oxygenase inhibitors). The effects of barium and ouabain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions

Metabolic responses to high pCO2 conditions at a CO2 vent site in juveniles of a marine isopod species assemblage

We are starting to understand the relationship between metabolic rate responses and species' ability to respond to exposure to high pCO2. However, most of our knowledge has come from investigations of single species. The examination of metabolic responses of closely related species with differing distributions around natural elevated CO2 areas may be useful to inform our understanding of their adaptive significance. Furthermore, little is known about the physiological responses of marine invertebrate juveniles to high pCO2, despite the fact they are known to be sensitive to other stressors, often acting as bottlenecks for future species success. We conducted an in situ transplant experiment using juveniles of isopods found living inside and around a high pCO2 vent (Ischia, Italy): the CO2 'tolerant' Dynamene bifida and 'sensitive' Cymodoce truncata and Dynamene torelliae. This allowed us to test for any generality of the hypothesis that pCO2 sensitive marine invertebrates may be those that experience trade-offs between energy metabolism and cellular homoeostasis under high pCO2 conditions. Both sensitive species were able to maintain their energy metabolism under high pCO2 conditions, but in C. truncata this may occur at the expense of [carbonic anhydrase], confirming our hypothesis. By comparison, the tolerant D. bifida appeared metabolically well adapted to high pCO2, being able to upregulate ATP production without recourse to anaerobiosis. These isopods are important keystone species; however, given they differ in their metabolic responses to future pCO2, shifts in the structure of the marine ecosystems they inhabit may be expected under future ocean acidification conditions

How does it feel to act together?

This paper on the phenomenology of joint agency proposes a foray into a little explored territory at the intersection of two very active domains of research: joint action and sense of agency. I explore two ways in which our experience of joint agency may differ from our experience of individual agency. First, the mechanisms of action specification and control involved in joint action are typically more complex than those present in individual actions, since it is crucial for joint action that people coordinate their plans and actions. I discuss the implications that these coordination requirements might have for the strength of the sense of agency an agent may experience for a joint action. Second, engagement in joint action may involve a transformation of agentive identity and a partial or complete shift from a sense of self-agency to a sense of we-agency. I discuss several factors that may contribute to shaping our sense of agentive identity in joint action

Population genomics of marine zooplankton

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Bucklin, Ann et al. "Population Genomics of Marine Zooplankton." Population Genomics: Marine Organisms. Ed. Om P. Rajora and Marjorie Oleksiak. Springer, 2018. doi:10.1007/13836_2017_9.The exceptionally large population size and cosmopolitan biogeographic distribution that distinguish many – but not all – marine zooplankton species generate similarly exceptional patterns of population genetic and genomic diversity and structure. The phylogenetic diversity of zooplankton has slowed the application of population genomic approaches, due to lack of genomic resources for closelyrelated species and diversity of genomic architecture, including highly-replicated genomes of many crustaceans. Use of numerous genomic markers, especially single nucleotide polymorphisms (SNPs), is transforming our ability to analyze population genetics and connectivity of marine zooplankton, and providing new understanding and different answers than earlier analyses, which typically used mitochondrial DNA and microsatellite markers. Population genomic approaches have confirmed that, despite high dispersal potential, many zooplankton species exhibit genetic structuring among geographic populations, especially at large ocean-basin scales, and have revealed patterns and pathways of population connectivity that do not always track ocean circulation. Genomic and transcriptomic resources are critically needed to allow further examination of micro-evolution and local adaptation, including identification of genes that show evidence of selection. These new tools will also enable further examination of the significance of small-scale genetic heterogeneity of marine zooplankton, to discriminate genetic “noise” in large and patchy populations from local adaptation to environmental conditions and change.Support was provided by the US National Science Foundation to AB and RJO (PLR-1044982) and to RJO (MCB-1613856); support to IS and MC was provided by Nord University (Norway)

Investigating the Bidirectional Associations of Adiposity with Sleep Duration in Older Adults: The English Longitudinal Study of Ageing (ELSA)

Cross-sectional analyses of adiposity and sleep duration in younger adults suggest that increased adiposity is associated with shorter sleep. Prospective studies have yielded mixed findings, and the direction of this association in older adults is unclear. We examined the cross-sectional and potential bi-directional, prospective associations between adiposity and sleep duration (covariates included demographics, health behaviours, and health problems) in 5,015 respondents from the English Longitudinal Study of Ageing (ELSA), at baseline and follow-up. Following adjustment for covariates, we observed no significant cross-sectional relationship between body mass index (BMI) and sleep duration [(unstandardized) B?=??0.28?minutes, (95% Confidence Intervals (CI)?=??0.012; 0.002), p?=?0.190], or waist circumference (WC) and sleep duration [(unstandardized) B?=??0.10?minutes, (95% CI?=??0.004; 0.001), p?=?0.270]. Prospectively, both baseline BMI [B?=??0.42?minutes, (95% CI?=??0.013; ?0.002), p?=?0.013] and WC [B?=??0.18?minutes, (95% CI?=??0.005; ?0.000), p?=?0.016] were associated with decreased sleep duration at follow-up, independently of covariates. There was, however, no association between baseline sleep duration and change in BMI or WC (p?>?0.05). In older adults, our findings suggested that greater adiposity is associated with decreases in sleep duration over time; however the effect was very small

Ευρετικές προσεγγίσεις του μοναδιάστατου προβλήματος πακετοποίησης

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and non-pleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data

Mesenchymal stromal cells and vascular morphogenesis: gene expression profiles and promoting pathways

Objective: Hematopoietic cells and mesenchymal stromal cells are closely related to endothelial cells in theembryological cell differentiation lineages. To study the pathobiology of vascular immunology and microenvironmentin vascular morphogenesis, we analyzed the genetic factors known to be involved in vascular anomalies in humansand mice in the expression data from the Immunological Genome Project (ImmGen).Methods: We mined the Pictures of Standard Syndromes of Undiagnosed Malformations and NCBI OnlineMendelian Inheritance in Man databases to construct a gene list related to vasculature. We studied the expressionsignatures of these genes in the ImmGen database. Hierarchical clustering analyses were performed using Partek®Genomics Suite 6.6. Next, the acquired clusters were separately investigated within Ingenuity Pathway Analysis(IPA). Based on these results we performed a Principal Component Analysis (PCA) with pericyte samples from aseparate database to investigate the relation with pericytes.Results: Our database queries resulted in a gene list of 438 genes related to vasculature, of which 384 could bestudied within the ImmGen data set. Through hierarchical clustering we identified five distinct clusters of whichone was specific for expression in mesenchymal cell lines. Next, using IPA we found various pathways related topericyte functions. A subsequent PCA with pericyte samples showed a close resemblance to specific stromal cells ofmesenchymal origin indicating shared expression profiles for vascular genes between pericytes and these cell types.These results indicate that the processes of Epithelial-Mesenchymal-Transition and or Endothelial-MesenchymalTransition underly the interaction between epithelial/endothelial cells and mesenchymal stromal cells in vascularmorphogenesis.Conclusion: In this data analysis study, we performed data fusion from various sources that may aid futuremechanistic and therapeutic studies in study design and cell type selection as well as provide a potential strategyto find therapeutic targets based on the specific pathological molecular mechanisms related to vascular anomalies

Mesenchymal stromal cells and vascular morphogenesis: gene expression profiles and promoting pathways

Objective: Hematopoietic cells and mesenchymal stromal cells are closely related to endothelial cells in theembryological cell differentiation lineages. To study the pathobiology of vascular immunology and microenvironmentin vascular morphogenesis, we analyzed the genetic factors known to be involved in vascular anomalies in humansand mice in the expression data from the Immunological Genome Project (ImmGen).Methods: We mined the Pictures of Standard Syndromes of Undiagnosed Malformations and NCBI OnlineMendelian Inheritance in Man databases to construct a gene list related to vasculature. We studied the expressionsignatures of these genes in the ImmGen database. Hierarchical clustering analyses were performed using Partek®Genomics Suite 6.6. Next, the acquired clusters were separately investigated within Ingenuity Pathway Analysis(IPA). Based on these results we performed a Principal Component Analysis (PCA) with pericyte samples from aseparate database to investigate the relation with pericytes.Results: Our database queries resulted in a gene list of 438 genes related to vasculature, of which 384 could bestudied within the ImmGen data set. Through hierarchical clustering we identified five distinct clusters of whichone was specific for expression in mesenchymal cell lines. Next, using IPA we found various pathways related topericyte functions. A subsequent PCA with pericyte samples showed a close resemblance to specific stromal cells ofmesenchymal origin indicating shared expression profiles for vascular genes between pericytes and these cell types.These results indicate that the processes of Epithelial-Mesenchymal-Transition and or Endothelial-MesenchymalTransition underly the interaction between epithelial/endothelial cells and mesenchymal stromal cells in vascularmorphogenesis.Conclusion: In this data analysis study, we performed data fusion from various sources that may aid futuremechanistic and therapeutic studies in study design and cell type selection as well as provide a potential strategyto find therapeutic targets based on the specific pathological molecular mechanisms related to vascular anomalies