Network Theoretical Approach to Explore Factors Affecting Signal Propagation and Stability in Dementia's Protein-Protein Interaction Network.

Dementia-a syndrome affecting human cognition-is a major public health concern given to its rising prevalence worldwide. Though multiple research studies have analyzed disorders such as Alzheimer's disease and Frontotemporal dementia using a systems biology approach, a similar approach to dementia syndrome as a whole is required. In this study, we try to find the high-impact core regulating processes and factors involved in dementia's protein-protein interaction network. We also explore various aspects related to its stability and signal propagation. Using gene interaction databases such as STRING and GeneMANIA, a principal dementia network (PDN) consisting of 881 genes and 59,085 interactions was achieved. It was assortative in nature with hierarchical, scale-free topology enriched in various gene ontology (GO) categories and KEGG pathways, such as negative and positive regulation of apoptotic processes, macroautophagy, aging, response to drug, protein binding, etc. Using a clustering algorithm (Louvain method of modularity maximization) iteratively, we found a number of communities at different levels of hierarchy in PDN consisting of 95 "motif-localized hubs", out of which, 7 were present at deepest level and hence were key regulators (KRs) of PDN (HSP90AA1, HSP90AB1, EGFR, FYN, JUN, CELF2 and CTNNA3). In order to explore aspects of network's resilience, a knockout (of motif-localized hubs) experiment was carried out. It changed the network's topology from a hierarchal scale-free topology to scale-free, where independent clusters exhibited greater control. Additionally, network experiments on interaction of druggable genome and motif-localized hubs were carried out where UBC, EGFR, APP, CTNNB1, NTRK1, FN1, HSP90AA1, MDM2, VCP, CTNNA1 and GRB2 were identified as hubs in the resultant network (RN). We finally concluded that stability and resilience of PDN highly relies on motif-localized hubs (especially those present at deeper levels), making them important therapeutic intervention candidates. HSP90AA1, involved in heat shock response (and its master regulator, i.e., HSF1), and EGFR are most important genes in pathology of dementia apart from KRs, given their presence as KRs as well as hubs in RN.

Insights into the molecular basis of hypergravity-induced root growth phenotype in bread wheat (Triticum aestivum L.).

Hypergravity is a condition where the force of gravity exceeds that on the surface of the Earth and can be simulated by centrifugation. Previously, a significant increase in root growth phenotype was observed when wheat seeds were exposed to hypergravity (10 g for 12 h). In the present study, we investigated the molecular basis of this change through root transcriptome. The data revealed a total of 3765 up-regulated and 2102 down-regulated transcripts in response to hypergravity. GO enrichment analysis revealed hormonal responses, cell division, and cell-wall-related terms were significantly enriched in hypergravity. The increased isoform level expression of transcripts involved in auxin biosynthesis, transport, and signaling was observed. Further, enhanced expression of cell division transcripts and down-regulation of cell number regulator genes suggests rapid cell division. Overexpression of cellulose and hemicellulose biosynthesis transcripts suggests demand for cell-wall constituents. Collectively, this study identified candidate genes associated with hypergravity-induced enhanced root growth.

Gene Expression Dynamics in Rice Peduncles at the Heading Stage.

Improving grain yield in the staple food crop rice has been long sought goal of plant biotechnology. One of the traits with significant impact on rice breeding programs is peduncle elongation at the time of heading failing which leads to significant reduction in grain yield due to incomplete panicle exsertion. To decipher transcriptional dynamics and molecular players underlying peduncle elongation, we performed RNA sequencing analysis of elongating and non-elongating peduncles in two Indian cultivars, Swarna and Pokkali, at the time of heading. Along with genes associated with cell division and cell wall biosynthesis, we observed significant enrichment of genes associated with auxins, gibberellins, and brassinosteroid biosynthesis/signaling in the elongating peduncles before heading in both the genotypes. Similarly, genes associated with carbohydrate metabolism and mobilization, abiotic stress response along with cytokinin, abscisic acid, jasmonic acid, and ethylene biosynthesis/signaling were enriched in non-elongating peduncles post heading. Significant enrichment of genes belonging to key transcription factor families highlights their specialized roles in peduncle elongation and grain filling before and after heading, respectively. A comparison with anther/pollen development-related genes provided 76 candidates with overlapping roles in anther/pollen development and peduncle elongation. Some of these are important for carbohydrate remobilization to the developing grains. These can be engineered to combat with incomplete panicle exsertion in male sterile lines and manipulate carbohydrate dynamics in grasses. Overall, this study provides baseline information about potential target genes for engineering peduncle elongation with implications on plant height, biomass composition and grain yields in rice.

Transcriptional trajectories of anther development provide candidates for engineering male fertility in sorghum.

Sorghum is a self-pollinated crop with multiple economic uses as cereal, forage, and biofuel feedstock. Hybrid breeding is a cornerstone for sorghum improvement strategies that currently relies on cytoplasmic male sterile lines. To engineer genic male sterility, it is imperative to examine the genetic components regulating anther/pollen development in sorghum. To this end, we have performed transcriptomic analysis from three temporal stages of developing anthers that correspond to meiotic, microspore and mature pollen stages. A total of 5286 genes were differentially regulated among the three anther stages with 890 of them exhibiting anther-preferential expression. Differentially expressed genes could be clubbed into seven distinct developmental trajectories using K-means clustering. Pathway mapping revealed that genes involved in cell cycle, DNA repair, regulation of transcription, brassinosteroid and auxin biosynthesis/signalling exhibit peak expression in meiotic anthers, while those regulating abiotic stress, carbohydrate metabolism, and transport were enriched in microspore stage. Conversely, genes associated with protein degradation, post-translational modifications, cell wall biosynthesis/modifications, abscisic acid, ethylene, cytokinin and jasmonic acid biosynthesis/signalling were highly expressed in mature pollen stage. High concurrence in transcriptional dynamics and cis-regulatory elements of differentially expressed genes in rice and sorghum confirmed conserved developmental pathways regulating anther development across species. Comprehensive literature survey in conjunction with orthology analysis and anther-preferential accumulation enabled shortlisting of 21 prospective candidates for in-depth characterization and engineering male fertility in sorghum.