Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression.

INTRODUCTION: In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution. METHOD: Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages). Six animals were used for each time point. Common patterns of gene expression across all time points were identified and related to biological function. RESULTS: The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle. This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor-Stat3 (signal transducer and activator of signalling-3) signalling. Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed. During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes. After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity. CONCLUSION: We provide a resource of mouse mammary gene expression data for download or online analysis. Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment

Suivi du Gecko Phelsuma serraticauda (Squamata : Gekkonidae) dans la région Atsinanana, dans l’est de Madagascar

Cette étude a été effectuée sur le Gecko Phelsuma serraticaudadurant les mois d’octobre et décembre 2008 dans 57 sites dans l’est et nord - est de Madagascar. Elle a pour objectifs de déterminer l’aire de distribution dans l’est de Madagascar et l’utilisation d’habitat de cette espèce pour sa conservation et son utilisation durable. La plupart des observations des individus sur les plantes sont sur le cocotier Cocos nucifera (84,3 % ) et le fruit de pain Artocarpus altilis (4,9 % ), avec 8,3 % sur le mur d’une maison en bois. Le nombre de P. serraticauda varie entre un et cinq par biotope avec une moyenne de 2,6 ± 0,2 pour l’ensemble des plantes et de 1,7 ± 0,4 pour les maisons. Parmi les 29 pieds de cocotier, 34 % sont occupés chacun par un seul individu mâle ou femelle, 14 % par deux femelles, 10 % par deux mâles, 10 % par un mâle et une femelle, et 10 % par deux mâles et une femelle. Le nombre moyen de mâle a été 1,06 ± 0,20 et 1,00 ± 0,15 pour la femelle. Sur les quatre maisons visitées, trois sont occupées chacune par une femelle et la dernière par trois mâles et deux femelles. Le nombre moyen de mâles a été 0,75 ± 0,75 et de 1,25 ± 0,25 pour les femelles. Phelsuma serraticauda est rarement trouvé sur des eucalyptus, Artocarpus heterophylllus et autres palmiers. Cette espèce n’est pas recensée dans la forêt humide de basse altitude d’Analalava, à la périphérie de la forêt littorale d’Antetezana et dans la plantation de Ravenala madagascariensis. L’analyse des matières fécales a montré que l’espèce se nourrit principalement d’araignées, coléoptères, hyménoptères, hémiptères et de leurs larves. Elle est sympatrique avec P. lineata et P. quadriocellata. La collecte de P. serraticauda dans la nature est allouée avec une autorisation légale et suivant le quota fixé par la CITES. Des cas de collecte illicite qui constitue une menace pour l’espèce de P. serraticauda, sont notés pendant cette étude. Compte tenu de l’état actuel des populations de P. serraticauda et de l’absence de mesures de conservation, un système de monitoring et un site de conservation pour cette espèce devraient être mis en place de toute urgence. Cette étude est la première réalisée sur cette espèce dans son état sauvage pour mieux comprendre ses besoins en termes d’habitat et les mesures de conservation à long terme de l’espèce.ABSTRACTThe diurnal gecko Phelsuma serraticauda has a restricted range in eastern and northeastern Madagascar. A study was undertaken in 57 sites mostly in Ivoloina and its surroundings areas in October (phase 1) and December (phase 2) 2008. The main objectives were to elucidate the distribution area in the east of Madagascar and to determine the habitat use of P. serraticauda to help ensure its conservation and sustainable use. Most of the observations on plants were from coconut tree Cocos nucifera (84.3 % ) and breadfruit Artocarpus altilis (Moraceae, 4.9 % ), with 8.3 % from houses. The number of P. serraticauda per biotope varied between one and five with means of 2.6 ± 0.2 for all plants and 1.7 ± 0.4 for the houses. Among the 29 coconut trees, 34 % were each occupied by one male or female, 14 % by two females, 10 % by two males, 10 % by one male and one female, 10 % by two males and one female. The mean number of male of P. serraticauda on the coconut trees was 1.06 ± 0.20 and 1.00 ± 0.15 for female. Among the four analysed houses, three were occupied by one female and one by three males and two females. The mean number of male P. serraticauda on the houses was 0.75 ± 0.75 and 1.25 ± 0.25 for female. Phelsuma serraticauda was also found infrequently on Eucalyptus sp., Artocarpus heterophyllus, and other palm trees such as Dypsis sp. This species of gecko was not recorded in the humid forest of Analalava, in the edge of the Antetezana littoral forest, and in the vast plantation of Ravenala madagascariensis situated in the surrounding-areas of Ivoloina. Results from faecal analysis showed that P. serraticauda prey mostly on spiders, coleopterans and hymenopterans, hemipterans and their larvae. Phelsuma serraticauda was found sympatrically with P. lineata and P. quadriocellata. The collection of this species in the wild is allowed with legal authorization and with respect to the quotas fixed by CITES. We have noted cases of illegal collection of P. serraticauda during this study. The trade constitutes a threat for this gecko. Its populations are fragmented and are also threatened by habitat loss. Bearing in mind the lack of current conservation measures and the present state of the populations of P. serraticauda, a monitoring system and a conservation site for this species should be urgently established. This study is the first on this species in the wild and constitutes the beginning of many studies needed to better understand its habitat requirements and to ensure the long term survival of the species

Salience Attribution and its Relationship to Cannabis-Induced Psychotic Symptoms

BACKGROUND: Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity. METHODS: We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test (SAT), a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory (PSI). Dopamine synthesis capacity, indexed as the influx rate constant Kicer, was measured in 10 users and 6 controls with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine positron emission tomography. RESULTS: There was no significant difference in aberrant salience between the groups (F1,32 = 1.12, p=.30 [implicit]; F1,32=1.09, p=.30 [explicit]). Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r=.61, p=.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F1,15= 5.8, p=.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r=-.91, p=.01), whereas this relationship was non-significant within users (difference between correlations: Z=-2.05, p=.04). CONCLUSIONS: Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use

Additive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Compassionate Imagery on Self-Compassion in Recreational Users of Ecstasy

3,4-Methylenedioxymethylamphetamine (MDMA;‘ecstasy’) produces prosocial subjective effects that may extend to affiliative feelings towards the self. Behavioural techniques can produce similar self-directed affiliation. For example, compassionate imagery (CI) and ecstasy reduce self-criticism and increase self-compassion to a similar extent, with the effects of CI enhanced in the presence of ecstasy. Here, we examine self-compassion and self-criticism in recreational users who consumed chemically verified MDMA in a within-subjects crossover study. In a naturalistic setting, polydrug-using participants performed a self-focused CI exercise on two occasions separated by ≥6 days: once having consumed self-sourced MDMA and once not. Effects on state self-criticism, self-compassion and emotional empathy were assessed before and after MDMA use (or over an extended baseline period on the occasion that MDMA was not consumed) and reassessed after CI. In participants (n = 20; 8 women) whose ecstasy contained MDMA and no other drug, CI and MDMA appeared to separately increase emotional empathy (to critical facial expressions) and self-compassion. The effects of CI and MDMA on self-compassion also appeared to be additive. Establishing the observed effects in controlled studies will be critical for determining the combined utility of these approaches in fostering adaptive self-attitudes in a therapeutic context

Behavioral states may be associated with distinct spatial patterns in electrocorticogram

To determine if behavioral states are associated with unique spatial electrocorticographic (ECoG) patterns, we obtained recordings with a microgrid electrode array applied to the cortical surface of a human subject. The array was constructed with the intent of extracting maximal spatial information by optimizing interelectrode distances. A 34-year-old patient with intractable epilepsy underwent intracranial ECoG monitoring after standard methods failed to reveal localization of seizures. During the 8-day period of invasive recording, in addition to standard clinical electrodes a square 1 × 1 cm microgrid array with 64 electrodes (1.25 mm separation) was placed on the right inferior temporal gyrus. Careful review of video recordings identified four extended naturalistic behaviors: reading, conversing on the telephone, looking at photographs, and face-to-face interactions. ECoG activity recorded with the microgrid that corresponded to these behaviors was collected and ECoG spatial patterns were analyzed. During periods of ECoG selected for analysis, no electrographic seizures or epileptiform patterns were present. Moments of maximal spatial variance are shown to cluster by behavior. Comparisons between conditions using a permutation test reveal significantly different spatial patterns for each behavior. We conclude that ECoG recordings obtained on the cortical surface with optimal high spatial frequency resolution reveal distinct local spatial patterns that reflect different behavioral states, and we predict that similar patterns will be found in many if not most cortical areas on which a microgrid is placed

Antimicrobial metal-based thiophene derived compounds

A novel series of thiophene derived Schiff bases and their transition metal- [Co(II), Cu(II), Zn(II), Ni(II)] based compounds are reported. The Schiff bases act as tridentate ligands toward metal ions via azomethine-N, deprotonated-N of ammine substituents and S-atom of thienyl moiety. The synthesized ligands along with their metal complexes were screened for their in vitro antibacterial activity against six bacterial pathogens (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and for antifungal activity against six fungal pathogens (Trichophytonlongifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata). The results of antimicrobial studies revealed the free ligands to possess potential activity which significantly increased upon chelation

A measure of individual role in collective dynamics

Identifying key players in collective dynamics remains a challenge in several research fields, from the efficient dissemination of ideas to drug target discovery in biomedical problems. The difficulty lies at several levels: how to single out the role of individual elements in such intermingled systems, or which is the best way to quantify their importance. Centrality measures describe a node's importance by its position in a network. The key issue obviated is that the contribution of a node to the collective behavior is not uniquely determined by the structure of the system but it is a result of the interplay between dynamics and network structure. We show that dynamical influence measures explicitly how strongly a node's dynamical state affects collective behavior. For critical spreading, dynamical influence targets nodes according to their spreading capabilities. For diffusive processes it quantifies how efficiently real systems may be controlled by manipulating a single node.Comment: accepted for publication in Scientific Report

A meta-analysis of controlled trials of recombinant human activated protein C therapy in patients with sepsis

BACKGROUND: Meta-analysis of two randomised controlled trials in severe sepsis performed with recombinant human activated protein C may provide further insight as to the therapeutic utility of targeting the clotting cascade in this syndrome. METHODS: In search for relevant studies published, two randomized clinical trials were found eligible. RESULTS: The studies, PROWESS and ADDRESS, enrolled a total of 4329 patients with risk ratio (RR) and 95% confidence interval (CI) data for effect on 28-day mortality relative to control treatment of 0.92 (0.83–1.02) suggesting that recombinant human activated protein C is not beneficial in severe sepsis. In PROWESS, 873 of 1690 patients presented with low risk, and 2315 of 2639 patients in ADDRESS as defined by APACHE II score < 25. In this low-risk stratum, no effect of recombinant human activated protein C administration on 28-day mortality was observed. This observation appears to be consistent and homogenous. Heterogeneity between the two studies, however, was seen in patients with APACHE II score ≥ 25 in whom recombinant activated protein C was effective in PROWESS (n = 817; RR 0.71, CI 0.59–0.85) whereas a tendency toward harm was present in ADDRESS (n = 324; RR 1.21, CI 0.85–1.74). Even though the overall treatment effect in this high-risk population was still in favour of treatment with recombinant activated protein C (n = 1141; RR 0.80, CI 0.68–0.94), the observed heterogeneity suggests that the efficacy of recombinant human activated protein C is not robust. Not unlikely, the adverse tendency observed could have become significant with higher statistical power would ADDRESS not have been terminated prematurely. CONCLUSION: This meta-analysis, therefore, raises doubts about the clinical usefulness of recombinant activated protein C in patients with severe sepsis and an APACHE II score ≥ 25 which can only be resolved by another properly designed clinical trial