Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus

Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women

Study of Low Phytic Acid1-7 (lpa1-7), a New ZmMRP4 Mutation in Maize

Phytic acid (PA), myo-inositol 1,2,3,4,5,6-hexakisphosphate, is the main storage form of phosphorus in plants. It is localized in seeds, deposited as mixed salts of mineral cations in protein storage vacuoles; during germination, it is hydrolyzed by phytases. When seeds are used as food/feed, PA and the bound cations are poorly bioavailable for human and monogastric livestock due to their lack of phytase activity. Reducing the amount of PA is one strategy to solve these problems and is an objective of genetic improvement for improving the nutritional properties of major crops. In this work, we present data on the isolation of a new maize (Zea mays L.) low phytic acid 1 (lpa1) mutant allele obtained by chemical mutagenesis. This mutant, named lpa1-7, is able to accumulate less phytic phosphorus and a higher level of free inorganic phosphate in the seeds compared with wild type. It exhibits a monogenic recessive inheritance and lethality as homozygous. We demonstrate that in vitro cultivation can overcome lethality allowing the growth of adult plants, and we report data regarding embryo and leaf abnormalities and other defects caused by negative pleiotropic effects of this mutation

A paramutation phenomenon is involved in the genetics of maize low phytic acid1-241 (lpa1-241) trait

So far, in maize, three classes of mutants involved in phytic acid biosynthesis have been isolated: lpa1, lpa2 and lpa3. In 2007, a gene tagging experiment performed by Shi et al. found that mutations in ZmMRP4 ( multidrug resistance-associated proteins 4) gene cause lpa1 phenotype. In previous studies, we isolated and described a single recessive lpa mutation ( originally named lpa241), which was allelic to the lpa1-1 mutant, and was consequently renamed lpa1-241. It showed a decrease in the expression of the myo-inositol (Ins)-3-phosphate synthase gene (mips1S). In this study, we present genetic and molecular analyses of the lpa1-241 mutation that indicate an epigenetic origin of this trait, that is, a paramutagenic interaction that results in meiotically heritable changes in ZmMRP4 gene expression, causing a strong pleiotropic effect on the whole plant. The use of a 5-Azacytidine treatment provided data suggesting an association between gene methylation and the lpa1-241 phenotype. To our knowledge, this is the first report of a paramutagenic activity not involving flavonoid biosynthesis in maize, but regarding a key enzyme of an important metabolic pathway in plants

Evaluation of a possible use of brachytic 2 mutation in corn breeding

Aim. In maize Brachytic 2 (Br2) gene encodes for an auxin polar transporter similar to adenosine triphosphate (ATP)-binding cassette transporter of the multidrug resistant (MDR) class of P-glycopoteins (PGPs) protein family. Mutations in Br2 gene cause a reduction in plant stature (about 50%) due to shortening of the internodes length without a corresponding reduction in the number of internodes or in the size of other organs. Furthermore br2 mutation confers several positive agronomic traits such as stay green, resistance to lodging and in general a modified plant architecture mimicking modern hybrids. The aim of this work is to evaluate a possible application of br2 mutation as heterozygous (Br2/br2) in maize genetic improvement (in fact br2 mutation exhibits a phenomenon of incomplete dominance). Methods. With this purpose we constituted several hybrids differing only for br2 constitution (Br2/Br2 vs Br2/br2) and we compared some agronomic traits, such as plant height and ear height. We supported the breeding activity using a Sequence-Specific Amplification Polymorphism (S-SAP) molecular marker to confirm the presence of br2-23 mutation in the genetic material constituted. Results. The results obtained showed an useful effect of this mutation in some of the genetic backgrounds studied. Conclusion. Further breeding programs are necessary to explore the full potential of this new finding