Adiponectin accounts for gender differences in hepatocellular carcinoma incidence

Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α. This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics.G. Sabio is an investigator on the Ramón y Cajal Program. E. Manieri is a La Caixa Foundation fellow. L. Herrera-Melle is a fellow of the Ministerio de Educación, Cultura y Deporte (FPU15-05802). This study was funded by the following grants: G. Sabio was funded by the European Research Council (ERC 260464), European Foundation for the Study of Diabetes–Lilly, Ministerio de Ciencia, Innovación y Universidades (MICINN/SAF2016-79126-R), Comunidad de Madrid (B2017/BMD-3733), and BBVA Becas Leonardo a Investigadores y Creadores Culturales (Investigadores-BBVA-2017; IN[17]_BBM_BAS_0066); M. Marcos was funded by Instituto de Salud Carlos III and Federación Española de Enfermedades Raras (PI16/01548); and J.L. Torres was funded by Junta de Castilla y León GRS (1587/A/17). F.J. Cubero is a Ramón y Cajal Researcher (RYC-2014-15242) and a Gilead Liver Research Scholar 2018, and his work is supported by the Ministerio de Economia y Competitividad Retos (SAF2016-78711), Comunidad de Madrid (S2017/BMD-3727), The Alan Morement Memorial Fund Cholangiocarcinoma Charity (2018/117), the European Cooperation in Science and Technology Action (CA17112), and the European Foundation for Alcohol Research (EA14/18). L. Moran is a Comunidad de Madrid fellow (S2017/BMD-3727). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Electronic gaming machine characteristics: it's the little things that count

A range of gamblers, from low-frequency social gamblers through to problem gamblers in treatment, participated in focus groups discussing the characteristics of Electronic Gaming Machines (EGMs) that they found attractive. Analyses of the resulting transcripts resulted in two groups of EGM characteristics being identified as important, one group associated with winning and one with betting. Overall, free spin features were identified in all groups as the most attractive characteristic of EGMS. Beyond that it was smaller win-related characteristics, and low-denomination machines with multiple playable lines that were associated with increased duration and intensity of gambling behaviour. The important characteristics were consistent across different levels of gamblers, with the key behavioural difference being a self-reported ‘expertise’, and ‘strategic’ approach to gambling amongst higher-frequency gamblers and problem gamblers in treatment. The key characteristics all occur frequently and result in more wins and extended gambling sessions. The patterns identified resonated with established behavioural principles, and with models describing the development of problem gambling and addictions more generally

p38γ is essential for cell cycle progression and liver tumorigenesis

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)–cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease

Effect of within-session breaks in play on responsible gambling behaviour during sustained monetary losses

Rapid, continuous gambling formats are associated with higher risks for gambling-related harm in terms of excessive monetary and time expenditure. The current study investigated the effect on gambling response latency and persistence, of a new form of within-game intervention that required players to actively engage in response inhibition via monitoring for stop signals. Seventy-four experienced electronic gaming machine gamblers, with a mean age of 35.28 years, were recruited to participate in a rapid, continuous gambling task where real money could be won and lost. Participants were randomly allocated to either the control condition where no intervention was presented, or either a condition with a passive three minute break in play or a condition with a three minute intervention that required participants to engage in response inhibition. Although there was no main effect for experimental condition on gambling persistence, both interventions were effective in elevating response latency during a period of sustained losses. It was concluded that within-game interventions that create an enforced break in play are effective in increasing response latency between bets during periods of sustained losses. Furthermore, within-game interventions that require active involvement appear to be more effective in increasing response latency than standard, passive breaks in play

The relationship between gambling event frequency, motor response inhibition, arousal, and dissociative experience

Speed of play has been identified as a key structural characteristic in gambling behaviour, where games involving higher playing speeds enhance the experience of gambling. Of interest in the present study is the consistent finding that games with higher event frequencies are preferred by problem gamblers and are associated with more negative gambling outcomes, such as difficulty quitting the game and increased monetary loss. The present study investigated the impact of gambling speed of play on executive control functioning, focusing on how increased speeds of play impact motor response inhibition, and the potential mediating role arousal and dissociative experience play in this relationship. Fifty regular non-problem gamblers took part in a repeated-measures experiment where they gambled with real money on a simulated slot machine across five speed of play conditions. Response inhibition was measured using an embedded Go/No-Go task, where participants had to withhold motor responses, rather than operating the spin button on the slot machine when a specific colour cue was present. Results indicated that response inhibition performance was significantly worse during faster speeds of play, and that the role of arousal in this relationship was independent of any motor priming affect. The implications of these findings for gambling legislation and gambling harm-minimisation approaches are discussed

A p53-Dependent Response Limits Epidermal Stem Cell Functionality and Organismal Size in Mice with Short Telomeres

Telomere maintenance is essential to ensure proper size and function of organs with a high turnover. In particular, a dwarf phenotype as well as phenotypes associated to premature loss of tissue regeneration, including the skin (hair loss, hair graying, decreased wound healing), are found in mice deficient for telomerase, the enzyme responsible for maintaining telomere length. Coincidental with the appearance of these phenotypes, p53 is found activated in several tissues from these mice, where is thought to trigger cellular senescence and/or apoptotic responses. Here, we show that p53 abrogation rescues both the small size phenotype and restitutes the functionality of epidermal stem cells (ESC) of telomerase-deficient mice with dysfunctional telomeres. In particular, p53 ablation restores hair growth, skin renewal and wound healing responses upon mitogenic induction, as well as rescues ESCmobilization defects in vivo and defective ESC clonogenic activity in vitro. This recovery of ESC functions is accompanied by a downregulation of senescence markers and an increased proliferation in the skin and kidney of telomerase-deficient mice with critically short telomeres without changes in apoptosis rates. Together, these findings indicate the existence of a p53-dependent senescence response acting on stem/progenitor cells with dysfunctional telomeres that is actively limiting their contribution to tissue regeneration, thereby impinging on tissue fitness

Conséquences de la pollution urbaine sur la distribution d'eau d'alimentation publique à Abidjan

La croissance de la population abidjanaise qui a coïncidé avec le déclin de l'économie n'a pas permis le développement des infrastructures urbaines et des services communaux essentiels. Il s'en suit une insalubrité générale affectant la qualité des réserves en eau disponibles. Cette étude se propose, à partir des données du contrôle de qualité et au moyen d'une inspection sanitaire de déterminer l'origine de la pollution de l'eau souterraine de deux stations de production d'eau potable d'Abidjan. La méthodologie utilisée comprenait à la fois un contrôle sommaire de la qualité de l'eau et une inspection sanitaire effectuée à l'aide de fiches d'enquêtes. Les résultats d'analyses physico-chimiques et bactériologiques ont montré une concentration en nitrates et ammoniums supérieures aux directives OMS et CEE. La présence des indicateurs de pollution fécal notamment Escherichia Coli a été mis en évidence dans 5 forages. Ce qui témoigne d'une contamination des captages par les eaux usées. L'inspection sanitaire n'a pas révélé la présence de zone de culture ou d'élevage actuelle ou ancienne dans les périmètres inspectés. Elle a surtout indiqué l'existence de nombreuses fosses septiques autour des forages appartenant aux habitats situés dans les zones de captage. Les forages les plus contaminés étant les moins profonds et relativement éloignés les uns des autres laissent supposer l'existence de plusieurs sources de pollution. L'absence de périmètre de protection rapprochée autour des captages confirme bien la contamination des forages par les fosses septiques. Des mesures sanitaires urgentes s'imposent pour protéger les autres forages contre la pollution fécale due à une urbanisation accélérée

When transcriptomics and metabolomics work hand in hand A case study characterizing plant CDF transcription factors

Over the last three decades, novel "omics" platform technologies for the sequencing of DNA and complementary DNA (cDNA) (RNA-Seq), as well as for the analysis of proteins and metabolites by mass spectrometry, have become more and more available and increasingly found their way into general laboratory life. With this, the ability to generate highly multivariate datasets on the biological systems of choice has increased tremendously. However, the processing and, perhaps even more importantly, the integration of "omics" datasets still remains a bottleneck, although considerable computational and algorithmic advances have been made in recent years. In this mini-review, we use a number of recent "multi-omics" approaches realized in our laboratories as a common theme to discuss possible pitfalls of applying "omics" approaches and to highlight some useful tools for data integration and visualization in the form of an exemplified case study. In the selected example, we used a combination of transcriptomics and metabolomics alongside phenotypic analyses to functionally characterize a small number of Cycling Dof Transcription Factors (CDFs). It has to be remarked that, even though this approach is broadly used, the given workflow is only one of plenty possible ways to characterize target proteins