Spawning Induction in the Carp: Past Experience and Future Prospects - A Review

Most fish in aquaculture either fail to breed in captivity or their spawning occurs sporadically and late in the season. This is mainly due to the lack of natural cues in captivity, which leads to dysfunction of the endocrine axis regulating oocyte maturation and ovulation. Hypophysation as a remedy for this situation in fish has been employed in aquaculture since the 1930s and is still widely practiced. However, using crude pituitary homogenates in local hatcheries has frequently ended in failures that were attributed to the incon- sistent potency of the injected material and the unknown ovarian stage of the recipient fish. Since the mid 1980s, hypophysation has improved through the introduction of a standardized dry carp pituitary extract in which the luteinizing hormone (LH) content and activity have been calibrated (cal- ibrated carp pituitary extract = CCPE). Induction of spawning, however, is successful mainly in female cohorts in which 65% or more of the oocytes in an ovarian biopsy have migrating germinal vesicles. Further, due to decreasing quantities of industry-processed common carp and the expan- sion of ornamental carp production (koi and goldfish), the growing demand for CCPE could not be met, and an alternative had to be found. A hypo- thalamic approach, introduced into Israeli aquaculture in 1993 (called Dagin), combines a superactive analog of sGnRH (10 μg/kg), with the water-soluble dopamine (D2) receptor antagonist, metoclopramide (20 mg/kg). The progress of oocyte maturation in ovarian biopsies has been studied in parallel with changes in levels of LH, estradiol, and the matura- tion-inducing steroid (MIS; 17α, 20β, dihydroxy-4-pregnene-3-one). The hormone profile indicated that the gradual increases in LH and MIS follow- ing a single administration of Dagin were similar to those in fish treated with priming and resolving doses of CCPE. This would explain why Dagin is effective even when only a single injection is given, saving labor and reduc- ing handling stress. CCPE and Dagin were tested in parallel on common carp in a commercial hatchery. The spawning ratio and embryo viability were similar, although the latency between injection and ovulation was con- siderably longer and more variable in Dagin-treated than in CCPE-treated carp. It is recommended to use CCPE at the beginning and end of the spawning season when the LH content in the pituitary is low, and Dagin in mid-season and in field spawning. Future prospects raise the possibility that by employing molecular tools, a recombinant carp LH will be produced that will have the regular and expected potency of the hypophyseal approach without the risk of spreading pathogens from donor fish to broodstock. Work along this line is currently in progress

The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host's immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections

The Escherichia coli transcriptome mostly consists of independently regulated modules

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

EMA - A R package for Easy Microarray data analysis

<p>Abstract</p> <p>Background</p> <p>The increasing number of methodologies and tools currently available to analyse gene expression microarray data can be confusing for non specialist users.</p> <p>Findings</p> <p>Based on the experience of biostatisticians of Institut Curie, we propose both a clear analysis strategy and a selection of tools to investigate microarray gene expression data. The most usual and relevant existing R functions were discussed, validated and gathered in an easy-to-use R package (EMA) devoted to gene expression microarray analysis. These functions were improved for ease of use, enhanced visualisation and better interpretation of results.</p> <p>Conclusions</p> <p>Strategy and tools proposed in the EMA R package could provide a useful starting point for many microarrays users. EMA is part of Comprehensive R Archive Network and is freely available at <url>http://bioinfo.curie.fr/projects/ema/</url>.</p

Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review.

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4(+) enterocytes, microfold-like cells, and IL13RA2(+)IL11(+) inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and coregulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.Peer reviewe