Recent developments in Origins of Life research have focused on substantiating the narrative of an abiotic emergence of nucleic acids from organic molecules of low molecular weight, a paradigm that typically sidelines the roles of peptides. Nevertheless, the simple synthesis of amino acids, the facile nature of their activation and condensation, their ability to recognize metals and cofactors and their remarkable capacity to self-assemble make peptides (and their analogues) favourable candidates for one of the earliest functional polymers. In this mini-review, we explore the ramifications of this hypothesis. Diverse lines of research in molecular biology, bioinformatics, geochemistry, biophysics and astrobiology provide clues about the progression and early evolution of proteins, and lend credence to the idea that early peptides served many central prebiotic roles before they were encodable by a polynucleotide template, in a putative 'peptide-polynucleotide stage'. For example, early peptides and mini-proteins could have served as catalysts, compartments and structural hubs. In sum, we shed light on the role of early peptides and small proteins before and during the nucleotide world, in which nascent life fully grasped the potential of primordial proteins, and which has left an imprint on the idiosyncratic properties of extant proteins.

• Klíčová slova
• early peptides, origins of life, prebiotic polymers, protein evolution,
• MeSH
• nukleotidy MeSH
• nukleové kyseliny * MeSH
• peptidy chemie   MeSH
• proteiny MeSH
• původ života * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• nukleotidy MeSH
• nukleové kyseliny * MeSH
• peptidy MeSH
• proteiny MeSH

If we look at the history of our knowledge of nucleic acids, we would see in the distant past of 140 years Friedrich Miescher who had identified the acidic substance within the cell nucleus, which he called nuclein. About 70 years after his initial observation, this substance was connected with genetic information. This very substantial finding happened during the World War II. This was the impulse that research of nucleic acids received to speed up continuously growing mountain of information, which is more and more difficult to understand. Another eruption of new information about our genome was the result of ten years of intensive cooperation of many manufacturers divided into two competitive blocks which offered us knowledge of nucleotide sequence of all 46 DNA molecules. The year 2000 became the landmark marking the start of the postgenomic era. It did not mean that human genome was totally explored, but the cornerstone has been settled. Since then, we could concentrate our efforts on variability; use of the project of 1,000 genomes brought many important findings, eg. copy number variability (CNV) exceeds the single nucleotide polymophisms (SNP). Also intergenomic relationships, studies on function and pathways began to be much more understandable by elucidation of the genome primary structure. NGS as a tool also accelerated the epigenetic research. All this improved molecular diagnostics by discovering many new markers playing their role in disease and treatment and allowed us to enter the field of multifactorial illnesses including cancer. The progress in diagnostic technologies which has happened during the last decade forced our research teams to include other professions - eg. bioinformatics.

• MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• diagnostické techniky molekulární * MeSH
• lékařská genetika MeSH
• lidé MeSH
• nukleové kyseliny * genetika   dějiny   MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• historické články MeSH
• přehledy MeSH
• Názvy látek
• nukleové kyseliny * MeSH

Human papillomaviruses (HPVs) represent a diverse group of double-stranded DNA viruses associated with various types of cancers, notably cervical cancer. High-risk types of HPVs exhibit their oncogenic potential through the integration of their DNA into the host genome. This integration event contributes significantly to genomic instability and the progression of malignancy. However, traditional detection methods, such as immunohistochemistry or PCR-based assays, face inherent challenges, and thus alternative tools are being developed to fasten and simplify the analysis. Our study introduces an innovative biosensing platform that combines loop-mediated amplification with electrochemical (EC) analysis for the specific detection of HPV16 integration. By targeting key elements like the E7 mRNA, a central player in HPV integration, and the E2 viral gene transcript lost upon integration, we show clear distinction between episomal and integrated forms of HPV16. Our EC data confirmed higher E7 expression in HPV16-positive cell lines having integrated forms of viral genome, while E2 expression was diminished in cells with fully integrated genomes. Moreover, we revealed distinct expression patterns in cervical tissue of patients, correlating well with digital droplet PCR, qRT-PCR, or immunohistochemical staining. Our platform thus offers insights into HPV integration in clinical samples and facilitates further advancements in cervical cancer research and diagnostics.

• Klíčová slova
• HPV integration, RT‐LAMP, cervical cancer, electrochemistry, human papillomavirus,
• MeSH
• biosenzitivní techniky metody   MeSH
• DNA vazebné proteiny genetika   MeSH
• DNA virů genetika   MeSH
• elektrochemické techniky * metody   MeSH
• genom virový MeSH
• infekce papilomavirem * virologie   MeSH
• integrace viru * genetika   MeSH
• lidé MeSH
• lidský papilomavirus 16 * genetika   MeSH
• messenger RNA * genetika   MeSH
• nádory děložního čípku * virologie   MeSH
• onkogenní proteiny virové * genetika   MeSH
• Papillomavirus E7 - proteiny * genetika   MeSH
• progrese nemoci MeSH
• RNA virová genetika   MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• DNA virů MeSH
• E2 protein, Human papillomavirus type 16 MeSH Prohlížeč
• messenger RNA * MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové * MeSH
• Papillomavirus E7 - proteiny * MeSH
• RNA virová MeSH

Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. We furthermore developed a new approach to analyze the oscillating patterns of genome-wide DNA accessibility across the cell cycle, which revealed that SWI/SNF-dependent CRC binding sites are enriched at enhancers with peak accessibility during G1 phase, where they activate genes involved in cell-cycle progression. SWI/SNF inhibition strongly impairs G1-S transition and potentiates the ability of retinoids used clinically to induce cell-cycle exit. Similar cell-cycle effects in diverse SWI/SNF-addicted settings highlight G1-S transition as a common cause of SWI/SNF dependency. Our results illustrate that deeper knowledge of the temporal patterns of enhancer-related dependencies may aid the rational targeting of addicted cancers.

Cancer cells driven by runaway transcription factor networks frequently depend on the cellular machinery that promotes DNA accessibility. For this reason, recently developed small molecules that impair SWI/SNF (or BAF) chromatin remodeling activity have been under active evaluation as anti-cancer agents. However, exactly when SWI/SNF activity is essential in dependent cancers has remained unknown. By combining live-cell imaging and genome-wide profiling in neuroblastoma cells, Cermakova et al. discover that SWI/SNF activity is needed for survival only during G1 phase of the cell cycle. The authors reveal that in several cancer settings, dependency on SWI/SNF arises from the need to reactivate factors involved in G1-S transition. Because of this role, authors find that SWI/SNF inhibition potentiates cell-cycle exit by retinoic acid.

• MeSH
• buněčný cyklus MeSH
• chromatin genetika   MeSH
• DNA MeSH
• G1 fáze * MeSH
• lidé MeSH
• nádory * MeSH
• regulační oblasti nukleových kyselin MeSH
• restrukturace chromatinu MeSH
• transkripční faktory * metabolismus   MeSH
• zesilovače transkripce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chromatin MeSH
• DNA MeSH
• SWI-SNF-B chromatin-remodeling complex MeSH Prohlížeč
• transkripční faktory * MeSH

Selective, sensitive and affordable techniques to detect disease and underlying health issues have been developed recently. Biosensors as nanoanalytical tools have taken a front seat in this context. Nanotechnology-enabled progress in the health sector has aided in disease and pandemic management at a very early stage efficiently. This report reflects the state-of-the-art of nanobiosensor-based virus detection technology in terms of their detection methods, targets, limits of detection, range, sensitivity, assay time, etc. The article effectively summarizes the challenges with traditional technologies and newly emerging biosensors, including the nanotechnology-based detection kit for COVID-19; optically enhanced technology; and electrochemical, smart and wearable enabled nanobiosensors. The less explored but crucial piezoelectric nanobiosensor and the reverse transcription-loop mediated isothermal amplification (RT-LAMP)-based biosensor are also discussed here. The article could be of significance to researchers and doctors dedicated to developing potent, versatile biosensors for the rapid identification of COVID-19. This kind of report is needed for selecting suitable treatments and to avert epidemics.

• Klíčová slova
• COVID-19 detection, RT-LAMP, electrochemical, nanobiosensor, optical, piezoelectric, smart and wearable,
• MeSH
• biosenzitivní techniky * MeSH
• COVID-19 * MeSH
• lidé MeSH
• nanotechnologie MeSH
• pandemie MeSH
• SARS-CoV-2 MeSH
• senzitivita a specificita MeSH
• techniky amplifikace nukleových kyselin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6. The range of PASI score in psoriatic patients was 10-34 (median 19). In the patients, we found significantly elevated levels (p < 0.001) of cfDNA, nucleosomes, TNF-α, CRP, and IL-6. We did not find any significant relationship between the analyzed parameters in either group (i.e., experimental or control). Elevated levels of the biomarkers of inflammation (TNF-α, CRP, and IL-6) and the indicators of apoptosis (cfDNA, circulating nucleosomes) proved that exacerbated psoriasis vulgaris is associated with a high degree of systemic inflammatory responses and dysregulated apoptotic pathways.

• Klíčová slova
• Apoptosis, Cell-free DNA, Inflammation, Nucleosomes, Psoriasis,
• MeSH
• apoptóza MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• interleukin-6 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nukleozomy genetika   metabolismus   MeSH
• progrese nemoci MeSH
• psoriáza krev   patologie   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa krev   MeSH
• volné cirkulující nukleové kyseliny krev   MeSH
• zánět MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• C-reaktivní protein MeSH
• IL6 protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• nukleozomy MeSH
• TNF-alfa MeSH
• volné cirkulující nukleové kyseliny MeSH

Transient melting of the duplex-DNA (B-DNA) during DNA transactions allows repeated sequences to fold into non-B-DNA structures, including DNA junctions and G-quadruplexes. These noncanonical structures can act as impediments to DNA polymerase progression along the duplex, thereby triggering DNA damage and ultimately jeopardizing genomic stability. Their stabilization by ad hoc ligands is currently being explored as a putative anticancer strategy since it might represent an efficient way to inflict toxic DNA damage specifically to rapidly dividing cancer cells. The relevance of this strategy is only emerging for three-way DNA junctions (TWJs) and, to date, no molecule has been recognized as a reference TWJ ligand, featuring both high affinity and selectivity. Herein, we characterize such reference ligands through a combination of in vitro techniques comprising affinity and selectivity assays (competitive FRET-melting and TWJ Screen assays), functional tests (qPCR and Taq stop assays) and structural analyses (molecular dynamics and NMR investigations). We identify novel azacryptands TrisNP-amphi and TrisNP-ana as the most promising ligands, interacting with TWJs with high affinity and selectivity. These ligands represent new molecular tools to investigate the cellular roles of TWJs and explore how they can be exploited in innovative anticancer therapies.

• Klíčová slova
• DNA junctions, NMR, in vitro assays, ligands, molecular dynamics,
• MeSH
• DNA * chemie   MeSH
• G-kvadruplexy MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• ligandy MeSH
• molekulární struktura MeSH
• rezonanční přenos fluorescenční energie MeSH
• simulace molekulární dynamiky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA * MeSH
• ligandy MeSH

Telomeres are repeated sequences found at the end of the linear chromosomes of most eukaryotes and are required for chromosome integrity. Expression of the reverse-transcriptase telomerase allows for extension of telomeric repeats to counteract natural telomere shortening. Although Chlamydomonas reinhardtii, a photosynthetic unicellular green alga, is widely used as a model organism in photosynthesis and flagella research, and for biotechnological applications, the biology of its telomeres has not been investigated in depth. Here, we show that the C. reinhardtii (TTTTAGGG)n telomeric repeats are mostly nondegenerate and that the telomeres form a protective structure, with a subset ending with a 3' overhang and another subset presenting a blunt end. Although telomere size and length distributions are stable under various standard growth conditions, they vary substantially between 12 genetically close reference strains. Finally, we identify CrTERT, the gene encoding the catalytic subunit of telomerase and show that telomeres shorten progressively in mutants of this gene. Telomerase mutants eventually enter replicative senescence, demonstrating that telomerase is required for long-term maintenance of telomeres in C. reinhardtii.

• MeSH
• Chlamydomonas reinhardtii genetika   MeSH
• genetická variace MeSH
• homeostáza telomer MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• repetitivní sekvence nukleových kyselin MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• telomerasa chemie   genetika   metabolismus   MeSH
• telomery genetika   MeSH
• zkracování telomer MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• telomerasa MeSH

The development of metal-based antitumor drugs has been stimulated by the clinical success of cis-diamminedichloroplatinum(II) (cisplatin) and its analogs and by the clinical trials of other platinum and ruthenium complexes with activity against resistant tumors and reduced toxicity including orally available platinum drugs. Broadening the spectrum of antitumor drugs depends on understanding existing agents with a view toward developing new modes of attack. It is therefore of great interest to understand the details of molecular and biochemical mechanisms underlying the biological efficacy of platinum and other transition-metal compounds. There is a large body of experimental evidence that the success of platinum complexes in killing tumor cells results from their ability to form various types of covalent adducts on DNA; thus, the research of DNA interactions of metal-based antitumor drugs has predominated. The present review summarizes current knowledge on DNA modifications by platinum and ruthenium complexes, their recognition by specific proteins, and repair. It also provides strong support for the view that either platinum or ruthenium drugs, which bind to DNA in a fundamentally different manner from that of 'classical' cisplatin, have altered pharmacological properties. The present article also demonstrates that this concept has already led to the synthesis of several new unconventional platinum or ruthenium antitumor compounds that violate the original structure-activity relationships.

• MeSH
• adukty DNA účinky léků   metabolismus   MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• cisplatina analogy a deriváty   farmakologie   MeSH
• DNA nádorová účinky léků   metabolismus   MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• oprava DNA MeSH
• organokovové sloučeniny chemie   farmakologie   MeSH
• organoplatinové sloučeniny chemie   farmakologie   MeSH
• protein HMGB1 genetika   metabolismus   MeSH
• ruthenium farmakologie   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• stereoizomerie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adukty DNA MeSH
• antitumorózní látky MeSH
• cisplatina MeSH
• DNA nádorová MeSH
• organokovové sloučeniny MeSH
• organoplatinové sloučeniny MeSH
• protein HMGB1 MeSH
• ruthenium MeSH

Cell-free DNA (cfDNA) has recently been used as a non-invasive diagnostic tool for detecting tumour-specific mutations. cfDNA may also be used for monitoring disease progression and treatment response, but so far researchers focused on one or few genes only. A genomic profile may provide better information on patient prognosis compared to single specific mutations. In this hypothesis-generating study, we profiled by whole exome sequencing serial plasma samples from 10 colon cancer (CC) patients collected before and after 5-fluorouracil-based therapy, and one year after diagnosis to determine alterations associated with treatment response. In parallel, genome profiling was also performed in patients' corresponding tumour tissue to ascertain the molecular landscape of resistant tumours. The mutation concordance between cfDNA and tumour tissue DNA was higher in more advanced tumour stages than in the early stages of the disease. In non-responders, a specific mutation profile was observed in tumour tissues (TPSD1 p.Ala92Thr, CPAMD8 p.Arg341Gln, OBP2A p.ArgTyr123CysHis). A pathogenic APC mutation (p.Ser1315Ter) was detected only in cfDNA of one poor responder one year after the diagnosis and after therapy termination. Another poor responder presented a likely pathogenic TP53 mutation (p.Arg110Pro) in cfDNA of all plasma samplings and in tumour tissue. In conclusion, cfDNA could be used for genetic characterisation of CC patients and might be clinically useful for non-invasive therapy response monitoring.

• MeSH
• DNA nádorová * MeSH
• fluorouracil farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace * MeSH
• nádorové biomarkery * MeSH
• nádory tračníku krev   diagnóza   genetika   terapie   MeSH
• prognóza MeSH
• sekvenční analýza DNA MeSH
• senioři MeSH
• staging nádorů MeSH
• stupeň nádoru MeSH
• volné cirkulující nukleové kyseliny * MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA nádorová * MeSH
• fluorouracil MeSH
• nádorové biomarkery * MeSH
• volné cirkulující nukleové kyseliny * MeSH