The stringent response and physiological roles of (pp)pGpp in bacteria

The stringent response is a stress signalling system mediated by the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) in response to nutrient deprivation. Recent research highlights the complexity and broad range of functions that these alarmones control. This Review provides an update on our current understanding of the enzymes involved in ppGpp, pppGpp and guanosine 5′-monophosphate 3′-diphosphate (pGpp) (collectively (pp)pGpp) turnover, including those shown to produce pGpp and its analogue (pp)pApp. We describe the well-known interactions with RNA polymerase as well as a broader range of cellular target pathways controlled by (pp)pGpp, including DNA replication, transcription, nucleotide synthesis, ribosome biogenesis and function, as well as lipid metabolism. Finally, we review the role of ppGpp and pppGpp in bacterial pathogenesis, providing examples of how these nucleotides are involved in regulating many aspects of virulence and chronic infection

3D bioprinted nanocellulose-based hydrogels for tissue engineering applications: a brief review

Nanocellulosic materials, such as cellulose nanocrystals, cellulose nanofibers, and bacterial nanocellulose, that display high surface area, mechanical strength, biodegradability, and tunable surface chemistry have attracted great attention over the last decade for biomedical applications. Simultaneously, 3D printing is revolutionizing the field of biomedical engineering, which enables the fast and on-demand printing of customizable scaffolds, tissues, and organs. Nanocellulosic materials hold tremendous potential for 3D bioprinting due to their printability, their shear thinning behavior, their ability to live cell support and owing to their excellent biocompatibility. The amalgamation of nanocellulose-based feedstocks and 3D bioprinting is therefore of critical interest for the development of advanced functional 3D hydrogels. In this context, this review briefly discusses the most recent key developments and challenges in 3D bioprinting nanocellulose-based hydrogel constructs that have been successfully tested for mammalian cell viability and used in tissue engineering applications.Sandya S. Athukoralalage, Rajkamal Balu, Naba K. Dutta * and Namita Roy Choudhur

Polyelectrolyte gels: fundamentals, fabrication and applications

Polyelectrolyte gels are an important class of polymer gels and a versatile platform with charged polymer networks with ionisable groups. They have drawn significant recent attention as a class of smart material and have demonstrated potential for a variety of applications. This review begins with the fundamentals of polyelectrolyte gels, which encompass various classifications (i.e., origin, charge, shape) and crucial aspects (ionic conductivity and stimuli responsiveness). It further centralises recent developments of polyelectrolyte gels, emphasising their synthesis, structure–property relationships and responsive properties. Sequentially, this review demonstrates how polyelectrolyte gels’ flourishing properties create attractiveness to a range of applications including tissue engineering, drug delivery, actuators and bioelectronics. Finally, the review outlines the indisputable appeal, further improvements and emerging trends in polyelectrolyte gelsNisal Wanasingha, Pramod Dorishetty, Naba K. Dutta and Namita Roy Choudhur

Determining the importance of the stringent response for methicillin-resistant staphylococcus aureus virulence in vivo

The stringent response is a stress signaling pathway with links to bacterial virulence. This pathway is controlled by the nucleotide alarmone (p)ppGpp, produced in Staphylococcus aureus by 3 synthetase enzymes. Here, we used a panel of synthetase mutants to examine the importance of this signaling network for S. aureus survival and virulence in vivo. Using a zebrafish larval infection model, we observed that infection with a (p)ppGpp null strain attenuated virulence. Zebrafish myeloid cell depletion restored the virulence during systemic infection, indicating that (p)ppGpp is important for phagocyte-mediated immune evasion. Primary macrophages infection studies, followed by in vitro tolerance assays and RNA sequencing, revealed that (p)ppGpp is required to survive stressors found within the intracellular macrophage environment, with roles for each class of synthetase, and the linked transcription factor CodY, implicated. Taken together, these results define the importance of the stringent response and each class of synthetase for S. aureus infection

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Search for the Chiral Magnetic Effect in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV with the STAR forward Event Plane Detectors

A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at $\sqrt{s_{_{\rm{NN}}}}=27$ GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity $|\eta|<1.0$ and at forward rapidity $2.1 < |\eta|<5.1$. We compare the results based on the directed flow plane ($\Psi_1$) at forward rapidity and the elliptic flow plane ($\Psi_2$) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to $\Psi_1$ than to $\Psi_2$, while a flow driven background scenario would lead to a consistent result for both event planes[1,2]. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.Comment: main: 8 pages, 5 figures; supplementary material: 2 pages, 1 figur

Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Poly(ionic liquid)-stabilized graphene nanoinks for scalable 3D printing of graphene aerogels

Stable dispersions of pristine graphene in innocuous mediums are highly desired for the use of this 2D material into a variety of practical applications. Here, we report the direct layer-by-layer fabrication of high-quality graphene nanosheets in aqueous dispersions into three-dimensional graphene aerogels with hierarchical structure by freeze 3D printing. Water-soluble imidazolium-based poly(ionic liquid)s, which offer the synergy of high conductivity and π-stacking interactions with graphitic carbon, were prepared and utilized as stabilizers for graphite exfoliation in an aqueous medium. Stable and highly concentrated graphene dispersions in water with concentrations as high as 5 mg mL⁻¹ were obtained, which showed excellent ejectability through a wide range of nozzles. A freeze 3D printing technique was developed by integrating a precision dispensing system with a rapid cryogenization process using a Peltier module, advancing the capability to print the formulated graphene nanoinks into three-dimensional macroscopic structures. This technique provides a scalable and versatile process for layer-by-layer fabrication of 3D graphene aerogels, which may find importance in a myriad of applications, especially for batteries and supercapacitors.Tuan Sang Tran, Naba Kumar Dutta, and Namita Roy Choudhur