Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca(2+)) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism.

Iron (Fe) and zinc (Zn) are essential micronutrients required for proper development in both humans and plants. Rice (Oryza sativa L.) grains are the staple food for nearly half of the world’s population, but a poor source of metals such as Fe and Zn. Populations that rely on milled cereals are especially prone to Fe and Zn deficiencies, the most prevalent nutritional deficiencies in humans. Biofortification is a cost-effective solution for improvement of the nutritional quality of crops. However, a better understanding of the mechanisms underlying grain accumulation of mineral nutrients is required before this approach can achieve its full potential. Characterization of gene function is more time-consuming in crops than in model species such as Arabidopsis thaliana. Aiming to more quickly characterize rice genes related to metal homeostasis, we applied the concept of high throughput elemental profiling (ionomics) to Arabidopsis lines heterologously expressing rice cDNAs driven by the 35S promoter, named FOX (Full Length Over-eXpressor) lines. We screened lines expressing candidate genes that could be used in the development of biofortified grain. Among the most promising candidates, we identified two lines ovexpressing the metal cation transporter OsZIP7. OsZIP7 expression in Arabidopsis resulted in a 25% increase in shoot Zn concentrations compared to non-transformed plants. We further characterized OsZIP7 and showed that it is localized to the plasma membrane and is able to complement Zn transport defective (but not Fe defective) yeast mutants. Interestingly, we showed that OsZIP7 does not transport Cd, which is commonly transported by ZIP proteins. Importantly, OsZIP7-expressing lines have increased Zn concentrations in their seeds. Our results indicate that OsZIP7 is a good candidate for developing Zn biofortified rice. Moreover, we showed the use of heterologous expression of genes from crops in A. thaliana as a fast method for characterization of crop genes related to the ionome and potentially useful in biofortification strategies.

Iron (Fe) is an essential micronutrient that is frequently inaccessible to plants. Rice (Oryza sativa L.) plants employ the Combined Strategy for Fe uptake, which is composed by all features of Strategy II, common to all Poaceae species, and some features of Strategy I, common to non-Poaceae species. To understand the evolution of Fe uptake mechanisms, we analyzed the root transcriptomic response to Fe deficiency in O. sativa and its wild progenitor O. rufipogon. We identified 622 and 2,017 differentially expressed genes in O. sativa and O. rufipogon, respectively. Among the genes up-regulated in both species, we found Fe transporters associated with Strategy I, such as IRT1, IRT2 and NRAMP1; and genes associated with Strategy II, such as YSL15 and IRO2. In order to evaluate the conservation of these Strategies among other Poaceae, we identified the orthologs of these genes in nine species from the Oryza genus, maize and sorghum, and evaluated their expression profile in response to low Fe condition. Our results indicate that the Combined Strategy is not specific to O. sativa as previously proposed, but also present in species of the Oryza genus closely related to domesticated rice, and originated around the same time the AA genome lineage within Oryza diversified. Therefore, adaptation to Fe2+ acquisition via IRT1 in flooded soils precedes O. sativa domestication.

Iron (Fe) toxicity is one of the most common mineral disorders affecting rice (Oryza sativa) production in flooded lowland fields. Oryza meridionalis is endemic from Northern Australia and grows in regions with Fe rich soils, making it a candidate for use in adaptive breeding. Aiming to understand tolerance mechanisms in rice, we screened a population of interspecific introgression lines (IL) from a cross between O. sativa and O. meridionalis for the identification of QTLs contributing to Fe toxicity tolerance. Six putative QTLs were identified. A line carrying one introgression from O. meridionalis on chromosome 9 associated with one QTL was highly tolerant despite very high shoot Fe concentrations. Physiological, biochemical, ionomic and transcriptomic analyses showed that the IL tolerance could partly be explained by higher relative Fe retention in the leaf sheath and culm. We constructed the interspecific hybrid genome in silico for transcriptomic analysis, and identified differentially regulated introgressed genes from O. meridionalis that could be involved in shoot-based Fe tolerance, such as metallothioneins, glutathione S-transferases and transporters from ABC and MFS families. This work demonstrates that introgressions of O. meridionalis into the O. sativa genome can confer increased tolerance to excess Fe.

Autism is a neurodevelopmental disorder manifested by impaired social interaction, deficits in communication skills, restricted interests, and repetitive behaviors. In neurodevelopmental, neurodegenerative, and psychiatric disorders, glial cells undergo morphological, biochemical, and functional rearrangements, which are critical for neuronal development, neurotransmission, and synaptic connectivity. Cerebellar function is not limited to motor coordination but also contributes to cognition and may be affected in autism. Oligodendrocytes and specifically oligodendroglial precursors are highly susceptible to oxidative stress and excitotoxic insult. In the present study, we searched for evidence for developmental oligodendropathy in the context of autism by performing a network analysis of gene expression of cerebellar tissue. We created an in silico network model (OLIGO) showing the landscape of interactions between oligodendrocyte markers and demonstrated that more than 50 % (16 out of 30) of the genes within this model displayed significant changes of expression (corrected p value <0.05) in the cerebellum of autistic patients. In particular, we found up-regulation of OLIG2-, MBP-, OLIG1-, and MAG-specific oligodendrocyte markers. We postulate that aberrant expression of oligodendrocyte-specific genes, potentially related to changes in oligodendrogenesis, may contribute to abnormal cerebellar development, impaired myelination, and anomalous synaptic connectivity in autism spectrum disorders (ASD).