Less than 5 Netrin-1 molecules initiate attraction but 200 Sema3A molecules are necessary for repulsion

Guidance molecules, such as Sema3A or Netrin-1, induce growth cone (GC) repulsion or attraction. In order to determine the speed of action and efficiency of these guidance cues we developed an experimental procedure to deliver controlled amounts of these molecules. Lipid vesicles encapsulating 10-10 4 molecules of Sema3A or Netrin-1 were manipulated with high spatial and temporal resolution by optical tweezers and their photolysis triggered by laser pulses. Guidance molecules released from the vesicles diffused and reached the GC membrane in a few seconds. Following their arrival, GCs retracted or grew in 20-120 s. By determining the number of guidance molecules trapped inside vesicles and estimating the fraction of guidance molecules reaching the GC, we show that the arrival of less than 5 Netrin-1 molecules on the GC membrane is sufficient to induce growth. In contrast, the arrival of about 200 Sema3A molecules is necessary to induce filopodia repulsion

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

Competition between meiotic and apomictic pathways during ovule and seed development results in clonality

Meiotic and apomictic reproductive pathways develop simultaneously in facultative aposporous apomictic species, and compete to form a seed as final goal. This developmental competition was evaluated in tetraploid genotypes of Paspalum malacophyllum in order to understand the scanty rate of sexuality in facultative apomictic populations. Cyto-embryology on ovules, flow cytometry on seeds and progeny tests by DNA fingerprinting were used to measure the relative incidence of each meiotic or apomictic pathway along four different stages of the plant's life cycle, namely the beginning and end of gametogenesis, seed formation, and adult offspring. A high variation in the frequencies of sexual and apomictic pathways occurred at the first two stages. A trend of radical decline in realised sexuality was then observed. Sexual and apomictic seeds were produced, but the efficiency of the sexual pathway drastically dropped, and exclusively clonal offspring remained. Both reproductive pathways are unstable at the beginning of development, and only the apomictic one remains functional. Key factors reducing sexuality are the faster growth and parthenogenetic development of the aposporous pathway, and an (epi)genetically negative background related to the extensive gene de-regulation pattern responsible for apomixis. The effects of inbreeding depression during post-fertilisation development may further decrease frequencies of effective sexuality.Fil: Hojsgaard, Diego Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste. Instituto de Botánica del Nordeste (i); Argentina; University of Goettingen. Department of Systematic Botany. Albrecht-von-Haller Institute of Plant Sciences; Alemania;Fil: Martínez, Eric Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste. Instituto de Botánica del Nordeste (i); Argentina; Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias; Argentina;Fil: Quarin, Camilo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Nordeste. Instituto de Botánica del Nordeste (i); Argentina; Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias; Argentina