Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a mouse model of TLE using 100 epileptic and 100 control hippocampi shows the proconvulsive module is preserved across-species, specific to the epileptic hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3), and demonstrate that SESN3 positively regulates the module in macrophages, microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms the regulation of the transcriptional module, and attenuates chemically induced behavioural seizures in vivo

The presence of a systemic inflammatory response predicts poorer survival in patients receiving adjuvant 5-FU chemotherapy following potentially curative resection for colorectal cancer

There is increasing evidence that the presence of a systemic inflammatory response plays an important role in survival following curative resection for colorectal cancer. The present study evaluated the relationship between C-reactive protein concentrations and survival in a cohort of patients receiving adjuvant 5-fluorouracil (5-FU) chemotherapy following potentially curative resection for colorectal cancer. In all, 222 patients undergoing potentially curative resection for colorectal cancer were studied. Of these, 50 patients received adjuvant 5-FU-based chemotherapy. Circulating concentrations of C-reactive protein were measured prior to surgery. The minimum follow-up was 15 months; the median follow-up of the survivors was 38 months. During this period 61 patients died, 32 patients of their cancer and 29 of intercurrent disease. In those patients who did not receive adjuvant chemotherapy, age (P<0.001), Dukes stage (P<0.05) and an elevated C-reactive protein (P<0.01) were significantly associated with survival. In those patients who did receive adjuvant chemotherapy, an elevated C-reactive protein concentration (P<0.01) was significantly associated with survival. The presence of a systemic inflammatory response is an independent predictor of poor outcome in patients receiving adjuvant 5-FU-based chemotherapy following potentially curative resection for colorectal cancer

Pollination and dispersal trait spectra recover faster than the growth form spectrum during spontaneous succession in sandy old‐fields

Question: Spontaneous succession is the most natural and cost‐effective solution for grassland restoration. However, little is known about the time required for the recovery of grassland functionality, i.e., for the recovery of reproductive and vegetative processes typical of pristine grasslands. Since these processes operate at different scales, we addressed the question: do reproductive and vegetative processes require different recovery times during spontaneous succession? Location: Kiskunság sand region (Central Hungary). Methods: As combinations of plant traits can be used to highlight general patterns in ecological processes, we compared reproductive (pollination‐ and dispersal‐related) and vegetative (growth form) traits between recovered grasslands of different age (&lt;10 years old; 10–20 years old; 20–40 years old) and pristine grasslands. Results: During spontaneous succession, the reproductive trait spectra became similar to those of pristine grasslands earlier than the vegetative ones. In arable land abandoned for 10 years, pollination‐ and dispersal‐related trait spectra did not show significant difference to those of pristine grasslands; anemophily and anemochory were the prevailing strategies. Contrarily, significant differences in the growth form spectrum could be observed even after 40 years of abandonment; in recovered grasslands erect leafy species prevailed, while the fraction of dwarf shrubs and tussock‐forming species was significantly lower than in pristine grasslands. Conclusions: The recovery of the ecological processes of pristine grasslands might require different amounts of time, depending on the spatial scale at which they operate. The reproductive trait spectra recovered earlier than the vegetative one, since reproductive attributes first determine plant species sorting at the regional level towards their respective habitats. The recovery of the vegetative trait spectrum needs more time as vegetative‐based interactions operate on a smaller spatial scale. Thus, vegetative traits might be more effective in the long‐term assessment of restoration success than the reproductive ones

Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

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Plant community attributes affect dry grassland orchid establishment

Several factors have been taken into account to explain the distribution of orchid species. We explored the extent to which plant community attributes affect the abundance and reproductive fitness of three orchid species (Anacamptis morio, Himantoglossum adriaticum and Ophrys sphegodes), native to dry grasslands. Structural attributes of plant community (e.g. cover and height) were assessed in ninety 4 m(2) plots scattered on three hill massifs of the Veneto Region (NE Italy). For the three target orchid species, the height of the flowering stalk, the relative ramet height and the number of flowers and fruits were recorded in 203 tagged ramets. Generalized Linear Model revealed that plant community attributes such as cover and height of the herb layer exert a negative effect on the abundance of orchid populations. Furthermore, regression models indicated that O. sphegodes and H. adriaticum reproductive fitness, determined as fruit/flower ratio, was positively affected by relative ramet height. Our results revealed that local herbaceous vegetation structure influences the cover and fruit set of target orchid species. However, there can be substantial variation in the response of different species and variation in the structural attributes of surrounding vegetation may be associated with differences in the strength of selection. In order to achieve effective results in orchid species conservation, protocols for the in situ conservation must detail the range of vegetation covers and heights at which orchid species are favoured and can produce the most effective inflorescences

Are food-deceptive orchid species really functionally specialized for pollinators?

Food-deceptive orchid species have traditionally been considered pollination specialized to bees or butterflies. However, it is unclear to which concept of specialization this assumption is related; if to that of phenotypic specialization or of functional specialization. The main aim of this work was to verify if pollinators of five widespread food-deceptive orchid species (Anacamptis morio (L.) R.M. Bateman, Pridgeon & M.W. Chase, Anacamptis pyramidalis (L.) Rich., Himantoglossum adriaticum H. Baumann, Orchis purpurea Huds. and Orchis simia Lam.) predicted from the phenotypic point of view matched with the observed ones. We addressed the question by defining target orchids phenotypic specialization on the basis of their floral traits, and we compared the expected guilds of pollinators with the observed ones. Target orchid pollinators were collected by conducting a meta-analysis of the available literature and adding unpublished field observations, carried out in temperate dry grasslands in NE Italy. Pollinator species were subsequently grouped into guilds and differences in the guild spectra among orchid species grouped according to their phenotype were tested. In contradiction to expectations derived from the phenotypic point of view, food-deceptive orchid species were found to be highly functionally generalized for pollinators, and no differences in the pollinator guild spectra could be revealed among orchid groups. Our results may lead to reconsider food-deceptive orchid pollination ecology by revaluating the traditional equation orchid-pollination specialization