Computational approach for decoding malaria drug targets from single-cell transcriptomics and finding potential drug molecule.

Malaria is a deadly disease caused by Plasmodium parasites. While potent drugs are available in the market for malaria treatment, over the years, Plasmodium parasites have successfully developed resistance against many, if not all, front-line drugs. This poses a serious threat to global malaria eradication efforts, and the continued discovery of new drugs is necessary to tackle this debilitating disease.

Hybrid Diffusion Model for Stable, Affinity-Driven, Receptor-Aware Peptide Generation.

The convergence of biotechnology and artificial intelligence has the potential to transform drug development, especially in the field of therapeutic peptide design. Peptides are short chains of amino acids with diverse therapeutic applications that offer several advantages over small molecular drugs, such as targeted therapy and minimal side effects. However, limited oral bioavailability and enzymatic degradation have limited their effectiveness.

Country-specific optimization strategy for testing through contact tracing can help maintain a low reproduction number ([Formula: see text]) during unlock.

In response to the COVID19 pandemic, many countries have implemented lockdowns in multiple phases to ensure social distancing and quarantining of the infected subjects. Subsequent unlocks to reopen the economies started next waves of infection and imposed an extra burden on quarantine to keep the reproduction number ([Formula: see text]) < 1. However, most countries could not effectively contain the infection spread, suggesting identification of the potential sources weakening the effect of lockdowns could help design better informed lockdown-unlock cycles in the future.

Design of a MAPK signalling cascade balances energetic cost versus accuracy of information transmission.

Cellular processes are inherently noisy, and the selection for accurate responses in presence of noise has likely shaped signalling networks. Here, we investigate the trade-off between accuracy of information transmission and its energetic cost for a mitogen-activated protein kinase (MAPK) signalling cascade. Our analysis of the pheromone response pathway of budding yeast suggests that dose-dependent induction of the negative transcriptional feedbacks in this network maximizes the information per unit energetic cost, rather than the information transmission capacity itself.

Sharing of Phosphatases Promotes Response Plasticity in Phosphorylation Cascades.

Sharing of positive or negative regulators between multiple targets is frequently observed in cellular signaling cascades. For instance, phosphatase sharing between multiple kinases is ubiquitous within the MAPK pathway. Here we investigate how such phosphatase sharing could shape robustness and evolvability of the phosphorylation cascade.

Evolutionary Remodeling of Bacterial Motility Checkpoint Control.

Regulatory networks play a central role in the relationship between genotype and phenotype in all organisms. However, the mechanisms that underpin the evolutionary plasticity of these networks remain poorly understood. Here, we used experimental selection for enhanced bacterial motility in a porous environment to explore the adaptability of one of the most complex networks known in bacteria.

Sugar Influx Sensing by the Phosphotransferase System of Escherichia coli.

The phosphotransferase system (PTS) plays a pivotal role in the uptake of multiple sugars in Escherichia coli and many other bacteria. In the cell, individual sugar-specific PTS branches are interconnected through a series of phosphotransfer reactions, thus creating a global network that not only phosphorylates incoming sugars but also regulates a number of cellular processes. Despite the apparent importance of the PTS network in bacterial physiology, the holistic function of the network in the cell remains unclear.

Two distinct promoter architectures centered on dynamic nucleosomes control ribosomal protein gene transcription.

In yeast, ribosome production is controlled transcriptionally by tight coregulation of the 138 ribosomal protein genes (RPGs). RPG promoters display limited sequence homology, and the molecular basis for their coregulation remains largely unknown. Here we identify two prevalent RPG promoter types, both characterized by upstream binding of the general transcription factor (TF) Rap1 followed by the RPG-specific Fhl1/Ifh1 pair, with one type also binding the HMG-B protein Hmo1.

Phenotypic heterogeneity in mycobacterial stringent response.

Background: A common survival strategy of microorganisms subjected to stress involves the generation of phenotypic heterogeneity in the isogenic microbial population enabling a subset of the population to survive under stress. In a recent study, a mycobacterial population of M. smegmatis was shown to develop phenotypic heterogeneity under nutrient depletion.

Optimized point dose measurement for monitor unit verification in intensity modulated radiation therapy using 6 MV photons by three different methodologies with different detector-phantom combinations: A comparative study.

The study was aimed to compare accuracy of monitor unit verification in intensity modulated radiation therapy (IMRT) using 6 MV photons by three different methodologies with different detector phantom combinations. Sixty patients were randomly chosen. Zero degree couch and gantry angle plans were generated in a plastic universal IMRT verification phantom and 30×30×30 cc water phantom and measured using 0.

Positive feedback and noise activate the stringent response regulator rel in mycobacteria.

Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the two-component system MprAB and the sigma factor, SigE. SigE in turn activates the expression of the stringent response regulator, rel.

The p53-MDM2 network: from oscillations to apoptosis.

The p53 protein is well-known for its tumour suppressor function. The p53-MDM2 negative feedback loop constitutes the core module of a network of regulatory interactions activated under cellular stress. In normal cells, the level of p53 proteins is kept low by MDM2, i.

Gene copy number and cell cycle arrest.

The cell cycle is an orderly sequence of events which ultimately lead to the division of a single cell into two daughter cells. In the case of DNA damage by radiation or chemicals, the damage checkpoints in the G1 and G2 phases of the cell cycle are activated. This results in an arrest of the cell cycle so that the DNA damage can be repaired.

Noise characteristics of feed forward loops.

A prominent feature of gene transcription regulatory networks is the presence in large numbers of motifs, i.e., patterns of interconnection, in the networks.