Perinatal exposure to methoxychlor enhances adult cognitive responses and hippocampal neurogenesis in mice

International audienceDuring perinatal life, sex steroids, such as estradiol, have marked effects on the development and function of the nervous system. Environmental estrogens or xenoestrogens are man-made chemicals, which animal and human population encounter in the environment and which are able to disrupt the functioning of the endocrine system. Scientific interest in the effects of exposure to xenoestrogens has focused more on fertility and reproductive behaviors, while the effects on cognitive behaviors have received less attention. Therefore, the present study explored whether the organochlorine insecticide Methoxychlor (MXC), with known xenoestrogens properties, administered during the perinatal period (from gestational day 11 to postnatal day 8) to pregnant-lactating females, at an environmentally relevant dose (20 µg/kg (body weight)/day), would also affect learning and memory functions depending on the hippocampus of male and female offspring mice in adulthood. When tested in adulthood, MXC perinatal exposure led to an increase in anxiety-like behavior and in short-term spatial working memory in both sexes. Emotional learning was also assessed using a contextual fear paradigm and MXC treated male and female mice showed an enhanced freezing behavior compared to controls. These results were correlated with an increased survival of adult generated cells in the adult hippocampus. In conclusion, our results show that perinatal exposure to an environmentally relevant dose of MXC has an organizational effect on hippocampus-dependent memory and emotional behaviors

Exposure to Photoperiod-Melatonin-Induced, Sexually-Activated Rams after Weaning Advances the Resumption of Sexual Activity in Post-Partum Mediterranean Ewes Lambing in January

This study was aimed to determine whether the presence of sexually stimulated rams by photoperiodic and melatonin treatments can advance the resumption of post-partum sexual activity in Mediterranean ewes lambing in January and weaned at the end of the breeding season at 41°N, in March. Rams were exposed to two months of long days (16 h light/day) and given three melatonin implants at the end of the long days (sexually-activated rams; SAR). Control rams (CR) were exposed to the natural photoperiod. Thirty-six ewes weaned on 25 February were assigned to one of two groups. From 1 March to 30 June, one group was housed with four SAR males (SAR-treated; n = 18), and the other group (CR-treated; n = 18) was housed with four unstimulated rams. Ovulation was assessed once per week based on plasma progesterone concentrations. Estrus was monitored daily by marks left on ewes by rams’ harnesses. SAR-treated ewes had a shorter (p < 0.01) weaning–first estrus interval than CR-treated ewes (61 ± 17 days vs. 102 ± 47 days; mean date of first estrus after weaning on April 26 and June 6, respectively). The proportion of the ewes ovulating in April or May was higher (p < 0.05) in the SAR-treated group than in the CR-treated group. SAR-treated ewes resumed estrous activity sooner than CR-treated ewes such that, in April, May, and June, the proportion of females that exhibited estrus was higher (p < 0.01) in the SAR-treated group (72%, 89%, and 100%, respectively) than in the CR-treated group (17%, 44%, and 61%, respectively). In conclusion, the introduction at weaning of sexually activated rams advanced the resumption of estrous activity in ewes in spring. The practical implications of this work could be important in ewes adapted for intensive production and accelerated lambing systems

Male-induced early puberty correlates with the maturation of arcuate nucleus kisspeptin neurons in does

In goats, early exposure of spring-born females to sexually active bucks induces an early puberty onset assessed by the first ovulation. This effect is found when females are continuously exposed well before the male breeding season starting in September. The first aim of this study was to evaluate whether a shortened exposure of females to males could also lead to early puberty. We assessed the onset of puberty in Alpine does isolated from bucks (ISOL), exposed to wethers (CAS), exposed to intact bucks from the end of June (INT1), or mid-August (INT2). Intact bucks became sexually active in mid-September. At the beginning of October, 100% of INT1 and 90% of INT2 exposed does ovulated, in contrast to the ISOL (0%) and CAS (20%) groups. This demonstrated that contact with males that become sexually active is the main factor prompting precocious puberty in females. Furthermore, a reduced male exposure during a short window before the breeding season is sufficient to induce this phenomenon. The second aim was to investigate the neuroendocrine changes induced by male exposure. We found a significant increase in kisspeptin immunoreactivity (fiber density and number of cell bodies) in the caudal part of the arcuate nucleus of INT1 and INT2 exposed females. Thus, our results suggest that sensory stimuli from sexually active bucks (e.g., chemosignals) may trigger an early maturation of the ARC kisspeptin neuronal network leading to gonadotropin-releasing hormone secretion and first ovulation

Factually Consistent Summarization via Reinforcement Learning with Textual Entailment Feedback

Despite the seeming success of contemporary grounded text generation systems, they often tend to generate factually inconsistent text with respect to their input. This phenomenon is emphasized in tasks like summarization, in which the generated summaries should be corroborated by their source article. In this work, we leverage recent progress on textual entailment models to directly address this problem for abstractive summarization systems. We use reinforcement learning with reference-free, textual entailment rewards to optimize for factual consistency and explore the ensuing trade-offs, as improved consistency may come at the cost of less informative or more extractive summaries. Our results, according to both automatic metrics and human evaluation, show that our method considerably improves the faithfulness, salience, and conciseness of the generated summaries.Comment: ACL 202

Wer braucht heute noch die kirchliche Presse? Zehn (Chef-)Redakteure von Tageszeitungen zu den Perspektiven der katholischen Publizistik

Die katholische Presse in Deutschland steckt in einer existenziellen Krise. Über die gegenwärtige Situation liegen zahlreiche Analysen vor, aber kaum konkrete Vorstellungen, Pläne und Initiativen zur Um- und Neugestaltung. Darum hat Communicatio Socialis Redakteure in der säkularen Tagespresse um ihre persönliche, aus der Alltagspraxis erwachsene „Meinung von draußen“ gebeten über die Fragen, ob Kirchenpresse noch eine Rolle spielt für innerkirchliche Kommunika- tion, ob sie in der Öffentlichkeit überhaupt noch wahrgenommen wird oder ob ihre Aufgaben andere, nicht-kirchliche Medien erfüllen. Aus den Statements von zehn Journalisten geht hervor, dass sie die gegenwärtige Kirchenpresse trotz zahlreicher verlegerischer und redaktioneller Bemühungen als Auslaufmodell ansehen. Ihr wird jedoch nicht nur innerkirchlich, sondern auch in der Gesellschaft noch eine Aufgabe zugemessen, wenn sie als professionelles Printmedium mit Eigengesetzlichkeit im Herausgeber-, Verleger- und Redaktionsbereich gemacht werden und sie wirtschaftlich geführt werden können. EnglishWho needs still Church press? Ten (chief) editors from daily newspapers about perspectives of the catholic journalism The German Catholic Church press is facing an essential crisis. This is proofed by many analyses but there are no plans or initiatives to change the situation. Therefore, the author asked collegues from secular newspapers whether they think that Church press is still a necessary means for communication within the Church and into society, or whether other Church owned or private new media could take over their mission, or whether secular media and new social media could cover the existing interests in Church matters. In the opinion of ten secular editors the traditional Catholic Church press is even after many publishing and editorial updatings no model for the future. In general, most of the secular journalists see still a mission for Catholic newspapers as a special means of communication within the Church and into society if they were seen and made as professional print media with autonomous laws for publishers and editors. There are doubts, however, whether Church authorities would want them this way and economic existence could be made possible.

The main and accessory olfactory systems interact in the control of mate recognition and sexual behavior

Peer reviewe

Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer

Background: Crosstalk between neoplastic and stromal cells fosters prostate cancer (PCa) progression and dissemination. Insight in cell-to-cell communication networks provides new therapeutic avenues to mold processes that contribute to PCa tumor microenvironment (TME) alterations. Here we performed a detailed characterization of PCa tumor endothelial cells (TEC) to delineate intercellular crosstalk between TEC and the PCa TME. Methods: TEC isolated from 67 fresh radical prostatectomy (RP) specimens underwent multi-omic ex vivo characterization as well as orthogonal validation of both TEC functions and key markers by immunohistochemistry (IHC) and immunofluorescence (IF). To identify cell-cell interaction targets in TEC, we performed single-cell RNA sequencing (scRNA-seq) in four PCa patients who underwent a RP to catalogue cellular TME composition. Targets were cross-validated using IHC, publicly available datasets, cell culture expriments as well as a PCa xenograft mouse model. Results: Compared to adjacent normal endothelial cells (NEC) bulk RNA-seq analysis revealed upregulation of genes associated with tumor vasculature, collagen modification and extracellular matrix remodeling in TEC. PTGIR, PLAC9, CXCL12 and VDR were identified as TEC markers and confirmed by IF and IHC in an independent patient cohort. By scRNA-seq we identified 27 cell (sub)types, including endothelial cells (EC) with arterial, venous and immature signatures, as well as angiogenic tip EC. A focused molecular analysis revealed that arterial TEC displayed highest CXCL12 mRNA expression levels when compared to all other TME cell (sub)populations and showed a negative prognostic role. Receptor-ligand interaction analysis predicted interactions between arterial TEC derived CXCL12 and its cognate receptor CXCR4 on angiogenic tip EC. CXCL12 was in vitro and in vivo validated as actionable TEC target by highlighting the vessel number- and density- reducing activity of the CXCR4-inhibitor AMD3100 in murine PCa as well as by inhibition of TEC proliferation and migration in vitro. Conclusions: Overall, our comprehensive analysis identified novel PCa TEC targets and highlights CXCR4/CXCL12 interaction as a potential novel target to interfere with tumor angiogenesis in PCa