Restricted Set Of Genes Research Articles

An immune response characterizes early Alzheimer\u2019s disease pathology and subjective cognitive impairment in hydrocephalus biopsies

Early Alzheimer’s disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of biopsy β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Taken together, these findings highlight a restricted set of microglial and non-microglial genes that correlate with early AD pathology in the setting of subjective cognitive decline.

In marine Bacteroidetes the bulk of glycan degradation during algae blooms is mediated by few clades using a restricted set of genes

We investigated Bacteroidetes during spring algae blooms in the southern North Sea in 2010–2012 using a time series of 38 deeply sequenced metagenomes. Initial partitioning yielded 6455 bins, from which we extracted 3101 metagenome-assembled genomes (MAGs) including 1286 Bacteroidetes MAGs covering ~120 mostly uncultivated species. We identified 13 dominant, recurrent Bacteroidetes clades carrying a restricted set of conserved polysaccharide utilization loci (PULs) that likely mediate the bulk of bacteroidetal algal polysaccharide degradation. The majority of PULs were predicted to target the diatom storage polysaccharide laminarin, alpha-glucans, alpha-mannose-rich substrates, and sulfated xylans. Metaproteomics at 14 selected points in time revealed expression of SusC-like proteins from PULs targeting all of these substrates. Analyses of abundant key players and their PUL repertoires over time furthermore suggested that fewer and simpler polysaccharides dominated early bloom stages, and that more complex polysaccharides became available as blooms progressed.

Consistent Positive Co-Variation between Fluctuating Asymmetry and Sexual Trait Size: A Challenge to the Developmental Instability-Sexual Selection Hypothesis

The developmental instability (DI)-sexual selection hypothesis proposes that large size and symmetry in secondary sexual traits are favored by sexual selection because they reveal genetic quality. A critical prediction of this hypothesis is that there should exist negative correlations between trait fluctuating asymmetry (FA) and size of condition dependent sexual traits; condition dependent traits should reveal an organism’s overall health and vigor, and be influenced by a multitude of genetic loci. Here, we tested for the predicted negative FA-size correlations in the male sex comb of Drosophila bipectinata. Among field-caught males from five widely separated geographic localities, FA-size correlations were consistently positive, despite evidence that sex comb size is condition dependent. After controlling for trait size, FA was significantly negatively correlated with body size within several populations, indicating that developmental instability in the comb may reveal individual genetic quality. We suggest the possibility that condition dependent traits in some cases tap into independent units of the genome (a restricted set of genes), rather than signaling overall genetic properties of the organism. There were pronounced among-population differences in both comb FA and size, and these traits were positively correlated across populations, recapitulating the within-population patterns. We conclude that the results are inconsistent with the DI-sexual selection hypothesis, and discuss potential reasons for positive FA-size co-variation in sexual traits.

Thy1.2 driven expression of transgenic His6-SUMO2 in the brain of mice alters a restricted set of genes

Protein SUMOylation is a post-translational protein modification with a key regulatory role in nerve cell development and function, but its function in mammals in vivo has only been studied cursorily. We generated two new transgenic mouse lines that express His6-tagged SUMO1 and SUMO2 driven by the Thy1.2 promoter. The brains of mice of the two lines express transgenic His6-SUMO peptides and conjugate them to substrates in vivo but cytoarchitecture and synaptic organization of adult transgenic mouse brains are indistinguishable from the wild-type situation. We investigated the impact of transgenic SUMO expression on gene transcription in the hippocampus by performing genome wide analyses using microarrays. Surprisingly, no changes were observed in Thy1.2::His6-SUMO1 transgenic mice and only a restricted set of genes were upregulated in Thy1.2::His6-SUMO2 mice. Among these, Penk1 (Preproenkephalin 1), which encodes Met-enkephalin neuropeptides, showed the highest degree of alteration. Accordingly, a significant increase in Met-enkephalin peptide levels in the hippocampus of Thy1.2::His6-SUMO2 was detected, but the expression levels and cellular localization of Met-enkephalin receptors were not changed. Thus, transgenic neuronal expression of His6-SUMO1 or His6-SUMO2 only induces very minor phenotypical changes in mice.

Are rice (Oryza sativa L.) phosphate transporters regulated similarly by phosphate and arsenate? A comprehensive study.

Rice is one of the most important staple foods worldwide, but it often contains inorganic arsenic, which is toxic and gives rise to severe health problems. Rice plants take up arsenate As(V) via the phosphate transport pathways, though it is not known how As(V), as compared to phosphate, modifies the expression of phosphate transporters (PTs). Therefore, the impact of As(V) or phosphate (Pi) on the gene expression of PTs and several Pi signaling regulators was investigated. Rice plants were grown on medium containing different As(V) or Pi concentrations. Growth was evaluated and the expression of tested genes was quantified at different time points, using quantitative RT-PCR (qPCR). The As and P content in plants was determined using inductively coupled plasma mass spectrometry (ICP-MS). As(V) elicited diverse and opposite responses of different PTs in roots and shoots, while Pi triggered a more shallow and uniform transcriptional response in several tested genes. Only a restricted set of genes, including PT2, PT3, PT5 and PT13 and two SPX-MFS family members, was particularly responsive to As(V). Despite some common reactions, the responses of the analyzed genes were predominantly ion-specific. The possible reasons and consequences are discussed.

Identification of Genetic Modifiers of TDP-43 Neurotoxicity in Drosophila

Cytosolic aggregation of the nuclear RNA-binding protein TDP-43 is a histopathologic signature of degenerating neurons in amyotrophic lateral sclerosis (ALS), and mutations in the TARDBP gene encoding TDP-43 cause dominantly inherited forms of this condition. To understand the relationship between TDP-43 misregulation and neurotoxicity, we and others have used Drosophila as a model system, in which overexpression of either wild-type TDP-43 or its ALS-associated mutants in neurons is sufficient to induce neurotoxicity, paralysis, and early death. Using microarrays, we have examined gene expression patterns that accompany TDP-43-induced neurotoxicity in the fly system. Constitutive expression of TDP-43 in the Drosophila compound eye elicited widespread gene expression changes, with strong upregulation of cell cycle regulatory genes and genes functioning in the Notch intercellular communication pathway. Inducible expression of TDP-43 specifically in neurons elicited significant expression differences in a more restricted set of genes. Genes that were upregulated in both paradigms included SpindleB and the Notch target Hey, which appeared to be a direct TDP-43 target. Mutations that diminished activity of Notch or disrupted the function of downstream Notch target genes extended the lifespan of TDP-43 transgenic flies, suggesting that Notch activation was deleterious in this model. Finally, we showed that mutation of the nucleoporin Nup50 increased the lifespan of TDP-43 transgenic flies, suggesting that nuclear events contribute to TDP-43-dependent neurotoxicity. The combined findings identified pathways whose deregulation might contribute to TDP-43-induced neurotoxicity in Drosophila.

Nonsense-mediated mRNA decay of collagen – emerging complexity in RNA surveillance mechanisms

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved mRNA surveillance system that degrades mRNA transcripts that harbour a premature translation-termination codon (PTC), thus reducing the synthesis of truncated proteins that would otherwise have deleterious effects. Although extensive research has identified a conserved repertoire of NMD factors, these studies have been performed with a restricted set of genes and gene constructs with relatively few exons. As a consequence, NMD mechanisms are poorly understood for genes with large 3' terminal exons, and the applicability of the current models to large multi-exon genes is not clear. In this Commentary, we present an overview of the current understanding of NMD and discuss how analysis of nonsense mutations in the collagen gene family has provided new mechanistic insights into this process. Although NMD of the collagen genes with numerous small exons is consistent with the widely accepted exon-junction complex (EJC)-dependent model, the degradation of Col10a1 transcripts with nonsense mutations cannot be explained by any of the current NMD models. Col10a1 NMD might represent a fail-safe mechanism for genes that have large 3' terminal exons. Defining the mechanistic complexity of NMD is important to allow us to understand the pathophysiology of the numerous genetic disorders caused by PTC mutations.

Characterization of a Haloferax volcanii member of the enolase superfamily: deletion mutant construction, expression analysis, and transcriptome comparison

The enolase superfamily (COG4948) contains proteins with very different biological functions including regulators like the Escherichia coli RspA and metabolic enzymes like enolase. To unravel the biological function of an archaeal family member, an in frame deletion mutant of a gene encoding a COG4948 protein of Haloferax volcanii was generated. The mutant had a lag phase of 3 days after transition from a richer to a poorer medium, in contrast to the wild-type, and the gene was therefore named "important for transition" (iftA). After inoculation of fresh casamino acids or complex medium with stationary phase wild-type cells, the transcript level of iftA was transiently induced at the onset of growth. In contrast, in minimal (or "poor") glucose medium, both transcript and protein were present throughout growth, even in late stationary phase. A comparison of the transcriptomes of deletion mutant and wild-type revealed that transcript levels of a very restricted set of genes were differentially regulated, including genes encoding proteins involved in phosphate metabolism, regulators and stress response proteins. Taken together, the results indicate that IftA might have a dual function, i.e., transiently after transition to fresh medium and permanently during growth in glucose medium.

An orchestrated gene expression component of neuronal programmed cell death revealed by cDNA array analysis.

Programmed cell death (PCD) during neuronal development and disease has been shown to require de novo RNA synthesis. However, the time course and regulation of target genes is poorly understood. By using a brain-biased array of over 7,500 cDNAs, we profiled this gene expression component of PCD in cerebellar granule neurons challenged separately by potassium withdrawal, combined potassium and serum withdrawal, and kainic acid administration. We found that hundreds of genes were significantly regulated in discreet waves including known genes whose protein products are involved in PCD. A restricted set of genes was regulated by all models, providing evidence that signals inducing PCD can regulate large assemblages of genes (of which a restricted subset may be shared in multiple pathways).