Heavy metal-induced selection and proliferation of antibiotic resistance: A review

Antibiotic resistance is recognized as a global threat to public health. The selection and evolution of antibiotic resistance in clinical pathogens were believed to be majorly driven by the imprudent use of antibiotics. However, concerns regarding the same, through selection pressure by a multitude of other antimicrobial agents, such as heavy metals, are also growing. Heavy metal contamination co-selects antibiotic and metal resistance through numerous mechanisms, such as co-resistance and cross-resistance. Here, we have reviewed the role of heavy metals as antimicrobial resistance driving agents and the underlying concept and mechanisms of co-selection, while also highlighting the scarcity of studies explicitly inspecting the process of co-selection in clinical settings. Prospective strategies to manage heavy metal-induced antibiotic resistance have also been deliberated, underlining the need to find specific inhibitors so that alternate medicinal combinations can be added to the existing therapeutic armamentarium.     

Generation of hemipelvis surface geometry based on statistical shape modelling and contralateral mirroring

Biomechanics and Modeling in Mechanobiology - Personalised fracture plates manufactured using 3D printing offer an improved treatment option for unstable pelvic ring fractures that may not be...     

Global secretome analysis of resident cardiac progenitor cells from wild-type and transgenic heart failure mice: Why ambience matters

Resident cardiac progenitor cells (CPCs) have gained attention in cardiac regenerative medicine primarily due to their paracrine activity. In our current study we determined the role of pathological conditions such as heart failure on the autocrine-paracrine action of stem cell antigen-1 (Sca-1) expressing CPC. This comparative secretome profiling of Sca-1⁺ cells derived from transgenic heart failure (αMHC–cyclin-T1/Gαq overexpression [Cyc] cells) versus healthy (wild-type [Wt] cells) mice, achieved via mass-spectrometric quantification, enabled the identification of over 700 proteins. Our results demonstrate that the heart failure milieu caused a 2-fold enrichment of extracellular matrix proteins (ECM) like biglycan, versican, collagen XII, and angiogenic factors like heparan sulfate proteoglycan 2, plasminogen activator inhibitor 1 in the secretome. We further elucidated the direct influence of the secretome on the functional behavior of Sca-1 ⁺ cells via in vitro tube forming assay. Secreted factors present in the diseased milieu induced tube formation in Cyc cells (1.7-fold; p < 0.01) when compared with Wt cells after 24 hr of exposure. The presence of conditioned media moderately increased the proliferation of Cyc cells but had a more pronounced effect on Wt cells. Overall, these findings revealed global modifications in the secretory activity of adult Sca-1 ⁺ cells in the heart failure milieu. The secretion of ECM proteins and angiogenic factors, which are crucial for cardiac remodeling and recovery, was notably enriched in the supernatant of Cyc cells. Thus, during heart failure the microenvironment of Sca-1 ⁺ cells might favor angiogenesis and proliferation suggesting their potential to recover the damaged heart.     

Exploring membrane permeability of Tomatidine to enhance lipid mediated nucleic acid transfections

Intracellular delivery of nucleic acids is one of the critical steps in the transfections. Prior findings demonstrated various strategies including membrane fusion, endosomal escape for the efficient cytoplasmic delivery. In our continuing efforts to improve the nucleic acids transfections, we harnessed cell permeable properties of Tomatidine (T), a steroidal alkaloid abundantly found in green tomatoes for maximizing intracellular delivery of lipoplexes. We doped Tomatidine into liposomes of cationic lipid with amide linker (A) from our lipid library. Six liposomal formulations (AT) of Lipid A (1?mM) with varying concentrations of Tomatidine (0–1?mM) were prepared and evaluated for their transfection efficacies. Owing to its signature characteristic of cell membrane permeability, Tomatidine modulated endocytosis process, enhanced the intracellular delivery of the lipoplexes, and in turn increased the transfection efficacy of cationic liposomes. Our findings provide ‘proof of concept’ for enhancing transfections in gene delivery applications with Tomatidine in cationic liposomal formulations. These findings can be further applied in lipid mediated gene therapy and drug delivery applications.     

High diversity in Delta variant across countries revealed by genome‐wide analysis of SARS‐CoV‐2 beyond the Spike protein

The highly contagious Delta variant of SARS‐CoV‐2 has become a prevalent strain globally and poses a public health challenge around the world. While there has been extensive focus on understanding the amino acid mutations in the Delta variant’s Spike protein, the mutational landscape of the rest of the SARS‐CoV‐2 proteome (25 proteins) remains poorly understood. To this end, we performed a systematic analysis of mutations in all the SARS‐CoV‐2 proteins from nearly 2 million SARS‐CoV‐2 genomes from 176 countries/territories. Six highly prevalent missense mutations in the viral life cycle‐associated Membrane (I82T), Nucleocapsid (R203M, D377Y), NS3 (S26L), and NS7a (V82A, T120I) proteins are almost exclusive to the Delta variant compared to other variants of concern (mean prevalence across genomes: Delta = 99.74%, Alpha = 0.06%, Beta = 0.09%, and Gamma = 0.22%). Furthermore, we find that the Delta variant harbors a more diverse repertoire of mutations across countries compared to the previously dominant Alpha variant. Overall, our study underscores the high diversity of the Delta variant between countries and identifies a list of amino acid mutations in the Delta variant’s proteome for probing the mechanistic basis of pathogenic features such as high viral loads, high transmissibility, and reduced susceptibility against neutralization by vaccines.     

Adenine auxotrophic mutants of Aspergillus oryzae: development of a novel transformation system with triple auxotrophic hosts

adeA and adeB genes homologous to Saccharomyces cerevisiae ADE1 and ADE2, respectively, were cloned from Aspergillus oryzae. AdeA and AdeB share 62.8% and 52.5% identities with S. cerevisiae Ade1 and Ade2, respectively. In order to obtain triple auxotrophic mutants from A. oryzae, 12 red-colored mutant colonies were isolated by UV mutagenesis of a double auxotrophic host, NS4 (niaD(-), sC(-)), as a parent strain. All the mutants exhibited adenine auxotrophy and showed fluorescence in the vacuoles due to accumulation of a purine biosynthetic pathway precursor. Adenine auxotrophy of all the mutants was restored by introduction of either A. oryzae adeA or adeB genes. Sequence analysis demonstrated that substitutions or deletions of a single base pair occurred, inducing substitutions or frame shifts of amino acid sequences in both ade genes complementing the mutants. This study provides a novel host-vector system with triple auxotrophy in A. oryzae.     

In vitro study of the electromagnetic interaction between wireless phones and an implantable neural stimulator

Several clinical and laboratory studies have demonstrated electromagnetic interaction between implantable medical devices like pacemakers and cell phones being operated in close proximity. Those devices are largely now immune to phone interaction or procedures have been established to limit their interaction. The use of cell phones near people with implanted neural stimulators has not been studied. This research was initiated to investigate electromagnetic interaction between current cell phone technology and specific models of Cyberonics neural stimulators. Out of 1080 test runs conducted for this study, no interactions were observed, and it was concluded that the phone technologies examined in this study did not adversely affect the Cyberonics NeuroStar (Model 102) NeuroCybernetic Prosthesis (NCP) System. This article provides details on the experimental procedure that was used, which can also be used to test other neural stimulators and test technologies, and the results obtained.