Isothermal amplifications - a comprehensive review on current methods.

The introduction of nucleic acid amplification techniques has revolutionized the field of medical diagnostics in the last decade. The advent of PCR catalyzed the increasing application of DNA, not just for molecular cloning but also for molecular based diagnostics. Since the introduction of PCR, a deeper understanding of molecular mechanisms and enzymes involved in DNA/RNA replication has spurred the development of novel methods devoid of temperature cycling.

Ribosome-associated quality control and CAT tailing.

Translation is the set of mechanisms by which ribosomes decode genetic messages as they synthesize polypeptides of a defined amino acid sequence. While the ribosome has been honed by evolution for high-fidelity translation, errors are inevitable. Aberrant mRNAs, mRNA structure, defective ribosomes, interactions between nascent proteins and the ribosomal exit tunnel, and insufficient cellular resources, including low tRNA levels, can lead to functionally irreversible stalls.

Mechanisms linking endoplasmic reticulum (ER) stress and microRNAs to adipose tissue dysfunction in obesity.

Over accumulation of lipids in adipose tissue disrupts metabolic homeostasis by affecting cellular processes. Endoplasmic reticulum (ER) stress is one such process affected by obesity. Biochemical and physiological alterations in adipose tissue due to obesity interfere with adipose ER functions causing ER stress.

Cholesterol efflux pathways, inflammation, and atherosclerosis.

Plasma levels of high-density lipoprotein (HDL) inversely correlate with the incidence of cardiovascular diseases (CVD). The causal relationship between plasma HDL-cholesterol levels and CVD has been called into question by Mendelian randomization studies and the majority of clinical trials not showing any benefit of plasma HDL-cholesterol raising drugs on CVD. Nonetheless, recent Mendelian randomization studies including an increased number of CVD cases compared to earlier studies have confirmed that HDL-cholesterol levels and CVD are causally linked.

Modular optimization in metabolic engineering.

There is an increasing demand for bioproducts produced by metabolically engineered microbes, such as pharmaceuticals, biofuels, biochemicals and other high value compounds. In order to meet this demand, modular optimization, the optimizing of subsections instead of the whole system, has been adopted to engineer cells to overproduce products. Research into modularity has focused on traditional approaches such as DNA, RNA, and protein-level modularity of intercellular machinery, by optimizing metabolic pathways for enhanced production.

Guanine quadruplexes and their roles in molecular processes.

The role of guanine quadruplexes (G4) in fundamental biological processes like DNA replication, transcription, translation and telomere maintenance is recognized. G4 structure dynamics is regulated by G4 structure binding proteins and is thought to be crucial for the maintenance of genome integrity in both prokaryotic and eukaryotic cells. Growing research over the last decade has expanded the existing knowledge of the functional diversity of G4 (DNA and RNA) structures across the working models.

Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM).

DNA replication is a highly precise process which usually functions in a perfect rhythm with cell cycle progression. However, cells are constantly faced with various kinds of obstacles such as blocks in DNA replication, lack of availability of precursors and improper chromosome alignment. When these problems are not addressed, they may lead to chromosome instability and the accumulation of mutations, and even cell death.

The leucine-responsive regulatory proteins/feast-famine regulatory proteins: an ancient and complex class of transcriptional regulators in bacteria and archaea.

Since the discovery of the leucine-responsive regulatory protein (Lrp) almost 50 years ago, hundreds of Lrp homologs have been discovered, occurring in 45% of sequenced bacteria and almost all sequenced archaea. Lrp-like proteins are often referred to as the feast/famine regulatory proteins (FFRPs), reflecting their common regulatory roles. Acting as either global or local transcriptional regulators, FFRPs detect the environmental nutritional status by sensing small effector molecules (usually amino acids) and regulate the expression of genes involved in metabolism, virulence, motility, nutrient transport, stress tolerance, and antibiotic resistance to implement appropriate behaviors for the specific ecological niche of each organism.

Miro proteins connect mitochondrial function and intercellular transport.

Mitochondria are organelles present in most eukaryotic cells, where they play major and multifaceted roles. The classical notion of the main mitochondrial function as the powerhouse of the cell has been complemented by recent discoveries pointing to mitochondria as organelles affecting a number of other auxiliary processes. They go beyond the classical energy provision via acting as a relay point of many catabolic and anabolic processes, to signaling pathways critically affecting cell growth by their implication in pyrimidine synthesis.

Cancer cells dysregulate PI3K/AKT/mTOR pathway activation to ensure their survival and proliferation: mimicking them is a smart strategy of gammaherpesviruses.

The serine/threonine kinase mammalian target of rapamycin (mTOR) is the catalytic subunit of two complexes, mTORC1 and mTORC2, which have common and distinct subunits that mediate separate and overlapping functions. mTORC1 is activated by plenty of nutrients, and the two complexes can be activated by PI3K signaling. mTORC2 acts as an upstream regulator of AKT, and mTORC1 acts as a downstream effector.

Cellular mechanisms of mtDNA heteroplasmy dynamics.

Heteroplasmy refers to the coexistence of more than one variant of the mitochondrial genome (mtDNA). Mutated or partially deleted mtDNAs can induce chronic metabolic impairment and cause mitochondrial diseases when their heteroplasmy levels exceed a critical threshold. These mutant mtDNAs can be maternally inherited or can arise .

The role of non-genetic information in evolutionary frameworks.

The evolution of organisms has been a subject of paramount debate for hundreds of years and though major advances in the field have been made, the precise mechanisms underlying evolutionary processes remain fragmentary. Strikingly, the majority of the core principles accepted across the many fields of biology only consider genetic information as the major - if not exclusive - biological information carrier and thus consider it as the main evolutionary avatar. However, the real picture appears far more complex than originally anticipated, as compelling data suggest that nongenetic information steps up when highly dynamic evolutionary frameworks are explored.

How can a traffic light properly work if it is always green? The paradox of CK2 signaling.

CK2 is a constitutively active protein kinase that assuring a constant level of phosphorylation to its numerous substrates supports many of the most important biological functions. Nevertheless, its activity has to be controlled and adjusted in order to cope with the varying needs of a cell, and several examples of a fine-tune regulation of its activity have been described. More importantly, aberrant regulation of this enzyme may have pathological consequences, e.

SMART approaches for genome-wide analyses of skeletal muscle stem and niche cells.

Muscle stem cells (MuSCs) also called satellite cells are the building blocks of skeletal muscle, the largest tissue in the human body which is formed primarily of myofibers. While MuSCs are the principal cells that directly contribute to the formation of the muscle fibers, their ability to do so depends on critical interactions with a vast array of nonmyogenic cells within their niche environment. Therefore, understanding the nature of communication between MuSCs and their niche is of key importance to understand how the skeletal muscle is maintained and regenerated after injury.

ETF dehydrogenase advances in molecular genetics and impact on treatment.

Electron transfer flavoprotein dehydrogenase, also called ETF-ubiquinone oxidoreductase (ETF-QO), is a protein localized in the inner membrane of mitochondria, playing a central role in the electron-transfer system. Indeed, ETF-QO mediates electron transport from flavoprotein dehydrogenases to the ubiquinone pool. ETF-QO mutations are often associated with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD, OMIM#231680), a multisystem genetic disease characterized by various clinical manifestations with different degrees of severity.

Sweet systems: technologies for glycomic analysis and their integration into systems biology.

Found in virtually every organism, glycans are essential molecules that play important roles in almost every aspect of biology. The composition of glycome, the repertoire of glycans in an organism or a biological sample, is often found altered in many diseases, including cancer, infectious diseases, metabolic and developmental disorders. Understanding how glycosylation and glycomic changes enriches our knowledge of the mechanisms of disease progression and sheds light on the development of novel therapeutics.

A local regulatory network in the testis mediated by laminin and collagen fragments that supports spermatogenesis.

It is almost five decades since the discovery of the hypothalamic-pituitary-testicular axis. This refers to the hormonal axis that connects the hypothalamus, pituitary gland and testes, which in turn, regulates the production of spermatozoa through spermatogenesis in the seminiferous tubules, and testosterone through steroidogenesis by Leydig cells in the interstitium, of the testes. Emerging evidence has demonstrated the presence of a regulatory network across the seminiferous epithelium utilizing bioactive molecules produced locally at specific domains of the epithelium.

Regulation of the redox metabolome and thiol proteome by hydrogen sulfide.

Overproduction of reactive oxygen species and compromised antioxidant defenses perturb intracellular redox homeostasis and is associated with a myriad of human diseases as well as with the natural process of aging. Hydrogen sulfide (HS), which is biosynthesized by organisms ranging from bacteria to man, influences a broad range of physiological functions. A highly touted molecular mechanism by which HS exerts its cellular effects is via post-translational modification of the thiol redox proteome, converting cysteine thiols to persulfides, in a process referred to as protein persulfidation.

HIV suppressors against LINE-1: one functions as two.

Exogenous retroviruses are RNA viruses that require reverse transcription for their replication. Among these viruses, human immunodeficiency virus (HIV) is infectious to humans and causes the development of acquired immune deficiency syndrome (AIDS). There are also endogenous retroelements that require reverse transcription for their retrotransposition, among which the type 1 long interspersed element (LINE-1) is the only type of retroelement that can replicate autonomously.

Instrumental analysis of RNA modifications.

Organisms from all domains of life invest a substantial amount of energy for the introduction of RNA modifications into nearly all transcripts studied to date. Instrumental analysis of RNA can focus on the modified residues and reveal the function of these epitranscriptomic marks. Here, we will review recent advances and breakthroughs achieved by NMR spectroscopy, sequencing, and mass spectrometry of the epitranscriptome.

Coordinated roles of SLX4 and MutSβ in DNA repair and the maintenance of genome stability.

SLX4 provides a molecular scaffold for the assembly of multiple protein complexes required for the maintenance of genome stability. It is involved in the repair of DNA crosslinks, the resolution of recombination intermediates, the response to replication stress and the maintenance of telomere length. To carry out these diverse functions, SLX4 interacts with three structure-selective endonucleases, MUS81-EME1, SLX1 and XPF-ERCC1, as well as the telomere binding proteins TRF2, RTEL1 and SLX4IP.

Ribonucleotide incorporation into DNA during DNA replication and its consequences.

Ribonucleotides are the most abundant non-canonical nucleotides in the genome. Their vast presence and influence over genome biology is becoming increasingly appreciated. Here we review the recent progress made in understanding their genomic presence, incorporation characteristics and usefulness as biomarkers for polymerase enzymology.

Mobility and disorder in antibody and antigen binding sites do not prevent immunochemical recognition.

The known polyspecificity of antibodies, which is crucial for efficient immune response, is determined by the conformational flexibility and intrinsic disorder encoded in local peculiarities of the amino acid sequence of antibodies within or in the vicinity of their complementarity determining regions. Similarly, epitopes represent fuzzy binding sites, which are also characterized by local structural flexibility. Existing data suggest that the efficient interactions between antigens and antibodies rely on the conformational mobility and some disorder of their binding sites and therefore can be relatively well described by the "flexible lock - adjustable key" model, whereas both, extreme order (rigid lock-and-key) and extreme disorder (viral shape-shifters) are not compatible with the efficient antigen-antibody interactions and are not present in immune interactions.

The complexity and regulation of repair of alkylation damage to nucleic acids.

DNA damaging agents have been a cornerstone of cancer therapy for nearly a century. The discovery of many of these chemicals, particularly the alkylating agents, are deeply entwined with the development of poisonous materials originally intended for use in warfare. Over the last decades, their anti-proliferative effects have focused on the specific mechanisms by which they damage DNA, and the factors involved in the repair of such damage.

Multifaceted regulation of translation by the epitranscriptomic modification N-methyladenosine.

Translation occurring on cytoplasmic mRNA is precisely governed at three consecutive stages, including initiation, elongation and termination. A growing body of evidence has revealed that an emerging epitranscriptomic code N-methyladenosine (mA), asymmetrically present in a large subset of coding and non-coding transcripts, is crucially required for mediating the translatomic stability. Through recruiting translation machinery proteins, serving as a physical barrier, or directing RNA structural rearrangement and mRNA looping formation, mA has been decoded to modulate translational dynamics through potentially influencing the progress of different stages, thereby forming an additional layer of complexity to the regulation of translation.