Forced Overexpression and Knockout Analysis of SLC30A and SLC39A Family Genes Suggests Their Involvement in Establishing Resistance to Cisplatin in Human Cancer Cells.

The metabolism of zinc and manganese plays a pivotal role in cancer progression by mediating cancer cell growth and metastasis. The SLC30A family proteins and mediate the efflux of zinc, manganese, and probably other transition element ions outside the cytoplasm to the extracellular space or into intracellular membrane compartments. The SLC39A family members and are their functional antagonists that transfer these ions into the cytoplasm.

Study of activation cross sections of double neutron capture reaction on Ir for the reactor production route of radiotherapeutic Pt.

The radiotherapeutic Pt is among the most effective Auger electron emitters of the currently studied radionuclides that have a potential theranostic application in nuclear medicine. Production of Pt through double neuron capture of enriched Ir followed by β-decay to the radioisotope of interest carried out at the research reactor IBR-2 is described. Because of the high radiation background, radiochemical purification procedure of Pt from bulk of iridium was needed to be developed and is detailed here as well.

Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response.

Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains.

Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteins.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed.

AgeMeta: Quantitative Gene Expression Database of Mammalian Aging.

AgeMeta is a database that provides systemic and quantitative description of mammalian aging at the level of gene expression. It encompasses transcriptomic changes with age across various tissues of humans, mice, and rats, based on a comprehensive meta-analysis of 122 publicly available gene expression datasets from 26 studies. AgeMeta provides an intuitive visual interface for quantification of aging-associated transcriptomics at the level of individual genes and functional groups of genes, allowing easy comparison among various species and tissues.

Delocalized nonlinear vibrational modes and discrete breathers in β-FPUT simple cubic lattice.

The problem of finding various discrete breathers (DBs) in the β-Fermi-Pasta-Ulam-Tsingou simple cubic lattice is addressed. DBs are obtained by imposing localizing functions on delocalized nonlinear vibrational modes (DNVMs) having frequencies above the phonon spectrum of the lattice. Among 27 DNVMs with the wave vector at the boundary of the first Brillouin zone there are three satisfying this condition.

Nonequilibrium thermal rectification at the junction of harmonic chains.

A thermal diode or rectifier is a system that transmits heat or energy in one direction better than in the opposite direction. We investigate the influence of the distribution of energy among wave numbers on the diode effect for the junction of two dissimilar harmonic chains. An analytical expression for the diode coefficient, characterizing the difference between heat fluxes through the junction in two directions, is derived.

A Solitary Stalled 80S Ribosome Prevents mRNA Recruitment to Stress Granules.

In response to stress stimuli, eukaryotic cells typically suppress protein synthesis. This leads to the release of mRNAs from polysomes, their condensation with RNA-binding proteins, and the formation of non-membrane-bound cytoplasmic compartments called stress granules (SGs). SGs contain 40S but generally lack 60S ribosomal subunits.

Introduction of Dicistrovirus IRESs into UAS/SV40-polyA constructs results in premature polyadenylation and strong overexpression of the upstream ORF in animals.

To evaluate the properties of insect virus internal ribosomal entry sites (IRESs) for protein expression in , we have introduced Cricket Paralysis virus (CrPV) and Drosophila C virus (DCV) IRESs into UAS/SV40-polyA vector. We found that introduction of IRESs induce premature polyadenylation, resulting in both truncation of the mRNA, and an increase in mRNA levels of approximately 40-fold. The increase in mRNA levels was accompanied by increased resistance to nonsense-mediated mRNA decay (NMD)-mediated degradation.

Monitoring integrated stress response in live .

Cells exhibit stress responses to various environmental changes. Among these responses, the integrated stress response (ISR) plays a pivotal role as a crucial stress signaling pathway. While extensive ISR research has been conducted on cultured cells, our understanding of its implications in multicellular organisms remains limited, largely due to the constraints of current techniques that hinder our ability to track and manipulate the ISR in vivo.

Multi-omic rejuvenation and life span extension on exposure to youthful circulation.

Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is unknown. Here we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs.

Cell death or survival: Insights into the role of mRNA translational control.

Cellular stress is an intrinsic part of cell physiology that underlines cell survival or death. The ability of mammalian cells to regulate global protein synthesis (aka translational control) represents a critical, yet underappreciated, layer of regulation during the stress response. Various cellular stress response pathways monitor conditions of cell growth and subsequently reshape the cellular translatome to optimize translational outputs.

Influence of the internal degrees of freedom of coronene molecules on the nonlinear dynamics of a columnar chain.

The nonlinear dynamics of a one-dimensional molecular crystal in the form of a chain of planar coronene molecules is analyzed. Using molecular dynamics, it is shown that a chain of coronene molecules supports acoustic solitons, rotobreathers, and discrete breathers. An increase in the size of planar molecules in a chain leads to an increase in the number of internal degrees of freedom.

Distinct longevity mechanisms across and within species and their association with aging.

Lifespan varies within and across species, but the general principles of its control remain unclear. Here, we conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions. An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration.

Human Tissues Exhibit Diverse Composition of Translation Machinery.

While protein synthesis is vital for the majority of cell types of the human body, diversely differentiated cells require specific translation regulation. This suggests the specialization of translation machinery across tissues and organs. Using transcriptomic data from GTEx, FANTOM, and Gene Atlas, we systematically explored the abundance of transcripts encoding translation factors and aminoacyl-tRNA synthetases (ARSases) in human tissues.

In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan.

The FOXM1 transcription factor exhibits pleiotropic C-terminal transcriptional and N-terminal non-transcriptional functions in various biological processes critical for cellular homeostasis. We previously found that FOXM1 repression during cellular aging underlies the senescence phenotypes, which were vastly restored by overexpressing transcriptionally active FOXM1. Yet, it remains unknown whether increased expression of FOXM1 can delay organismal aging.

Discrete breathers in square lattices from delocalized nonlinear vibrational modes.

Standing and moving discrete breathers (or equally, intrinsic localized modes) in a square β-Fermi-Pasta-Ulam-Tsingou lattice are obtained by applying localizing functions to the delocalized nonlinear vibrational modes (DNVMs) found earlier by Ryabov and Chechin. The initial conditions used in our study do not correspond to exact spatially localized solutions, but make it possible to obtain long-lived quasibreathers. The approach employed in this work can easily be used to search for quasibreathers in three-dimensional crystal lattices, for which DNVMs with frequencies outside the phonon spectrum are known.

Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A.

Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s).

Relocalization of Translation Termination and Ribosome Recycling Factors to Stress Granules Coincides with Elevated Stop-Codon Readthrough and Reinitiation Rates upon Oxidative Stress.

Upon oxidative stress, mammalian cells rapidly reprogram their translation. This is accompanied by the formation of stress granules (SGs), cytoplasmic ribonucleoprotein condensates containing untranslated mRNA molecules, RNA-binding proteins, 40S ribosomal subunits, and a set of translation initiation factors. Here we show that arsenite-induced stress causes a dramatic increase in the stop-codon readthrough rate and significantly elevates translation reinitiation levels on uORF-containing and bicistronic mRNAs.

Enteroviruses Manipulate the Unfolded Protein Response through Multifaceted Deregulation of the Ire1-Xbp1 Pathway.

Many viruses are known to trigger endoplasmic reticulum (ER) stress in host cells, which in turn can develop a protective unfolded protein response (UPR). Depending on the conditions, the UPR may lead to either cell survival or programmed cell death. One of three UPR branches involves the upregulation of Xbp1 transcription factor caused by the unconventional cytoplasmic splicing of its mRNA.

Supersonic Motion of Atoms in an Octahedral Channel of fcc Copper.

In this work, the mass transfer along an octahedral channel in an fcc copper single crystal is studied for the first time using the method of molecular dynamics. It is found that the initial position of the bombarding atom, outside or inside the crystal, does not noticeably affect the dynamics of its motion. The higher the initial velocity of the bombarding atom, the deeper its penetration into the material.

Atom deposition and sputtering at normal incidence simulated by the Frenkel-Kontorova chain.

The impact of a molecule of N atoms with a speed of v_{0} on the free end of the Frenkel-Kontorova chain is numerically simulated. Depending on the values of N and v_{0}, different scenarios of the molecule-chain interaction are observed. Molecules with low speed stick to the chain.

Stability of Strained Stanene Compared to That of Graphene.

Stanene, composed of tin atoms, is a member of 2D-Xenes, two-dimensional single element materials. The properties of the stanene can be changed and improved by applying deformation, and it is important to know the range of in-plane deformation that the stanene can withstand. Using the Tersoff interatomic potential for calculation of phonon frequencies, the range of stability of planar stanene under uniform in-plane deformation is analyzed and compared with the known data for graphene.