Epigenetics and transgenerational inheritance.

Epigenetic modifications can alter the function of genes. The epigenetics changes are caused by environmental effects, which lead to chemical modifications of the DNA or the chromatin. The mechanisms involve the influence of small interfering siRNAs on gene silencing.

Phage Therapy in Germany-Update 2023.

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany.

The Roles of the Virome in Cancer.

Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces-which contain mainly bacteria and their viruses (phages)-from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders.

Within-Host and Between-Host Evolution in SARS-CoV-2-New Variant's Source.

Some of the newly emerging corona viral variants show high numbers of mutations. This is unexpected for a virus with a low mutation rate due to an inherent proof-reading system. Could such a variant arise under very special conditions occurring in a host where the virus replicates and mutates in a rather unlimited fashion, such as in immune compromised patients? The virus was shown to replicate in an immunosuppressed cancer patient for more than 105 days and might be a source of new variants.

Viroids and the Origin of Life.

Viroids are non-coding circular RNA molecules with rod-like or branched structures. They are often ribozymes, characterized by catalytic RNA. They can perform many basic functions of life and may have played a role in evolution since the beginning of life on Earth.

Phages Needed against Resistant Bacteria.

Phages have been known for more than 100 years. They have been applied to numerous infectious diseases and have proved to be effective in many cases. However, they have been neglected due to the era of antibiotics.

Air Microbiome and Pollution: Composition and Potential Effects on Human Health, Including SARS Coronavirus Infection.

Polluted air poses a significant threat to human health. Exposure to particulate matter (PM) and harmful gases contributes to cardiovascular and respiratory diseases, including allergies and obstructive lung disease. Air pollution may also be linked to cancer and reduced life expectancy.

What viruses tell us about evolution and immunity: beyond Darwin?

We describe mechanisms of genetic innovation mediated by viruses and related elements that, during evolution, caused major genetic changes beyond what was anticipated by Charles Darwin. Viruses and related elements introduced genetic information and have shaped the genomes and immune systems of all cellular life forms. None of these mechanisms contradict Darwin's theory of evolution but extend it by means of sequence information that has recently become available.

Viruses and Evolution - Viruses First? A Personal Perspective.

The discovery of exoplanets within putative habitable zones revolutionized astrobiology in recent years. It stimulated interest in the question about the origin of life and its evolution. Here, we discuss what the roles of viruses might have been at the beginning of life and during evolution.

Evolution of Immune Systems From Viruses and Transposable Elements.

Virus-derived sequences and transposable elements constitute a substantial portion of many cellular genomes. Recent insights reveal the intimate evolutionary relationship between these sequences and various cellular immune pathways. At the most basic level, superinfection exclusion may be considered a prototypical virus-mediated immune system that has been described in both prokaryotes and eukaryotes.

A Wake-Up Call: We Need Phage Therapy Now.

The rise of multidrug-resistant bacteria has resulted in an increased interest in phage therapy, which historically preceded antibiotic treatment against bacterial infections. To date, there have been no reports of serious adverse events caused by phages. They have been successfully used to cure human diseases in Eastern Europe for many decades.

RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense.

Retroviral infections are 'mini-symbiotic' events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT) and ribonuclease H (RNase H). These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation.

Fecal microbiota transplantation to fight infections and other intestinal diseases.

We have analyzed fecal bacterial and viral communities of a patient with recurrent infection (rCDI) who was cured by fecal microbiota transplantation (FMT). The "Zürich Patient" experienced immediate cure and has remained free of symptoms for now over 5 y. Donor-similar bacterial compositions after 4.

The intron-enriched HERV-K(HML-10) family suppresses apoptosis, an indicator of malignant transformation.

Background: Human endogenous retroviruses (HERVs) constitute 8% of the human genome and contribute substantially to the transcriptome. HERVs have been shown to generate RNAs that modulate host gene expression. However, experimental evidence for an impact of these regulatory transcripts on the cellular phenotype has been lacking.

Stable core virome despite variable microbiome after fecal transfer.

We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months).

Abolishing HIV-1 infectivity using a polypurine tract-specific G-quadruplex-forming oligonucleotide.

Background: HIV is primarily transmitted by sexual intercourse and predominantly infects people in Third World countries. Here an important medical need is self-protection for women, particularly in societies where condoms are not widely accepted. Therefore, availability of antiviral microbicides may significantly reduce sexual HIV transmission in such environments.

Long-term microbiota and virome in a Zürich patient after fecal transplantation against Clostridium difficile infection.

Fecal microbiota transplantation (FMT) is an emerging therapeutic option for Clostridium difficile infections that are refractory to conventional treatment. FMT introduces fecal microbes into the patient's intestine that prevent the recurrence of C. difficile, leading to rapid expansion of bacteria characteristic of healthy microbiota.

Long-term changes of bacterial and viral compositions in the intestine of a recovered Clostridium difficile patient after fecal microbiota transplantation.

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infections (RCDIs). However, long-term effects on the patients' gut microbiota and the role of viruses remain to be elucidated. Here, we characterized bacterial and viral microbiota in the feces of a cured RCDI patient at various time points until 4.

Transcriptional signature induced by a metastasis-promoting c-Src mutant in a human breast cell line.

Unlabelled: Deletions at the C-terminus of the proto-oncogene protein c-Src kinase are found in the viral oncogene protein v-Src as well as in some advanced human colon cancers. They are associated with increased kinase activity and cellular invasiveness. Here, we analyzed the mRNA expression signature of a constitutively active C-terminal mutant of c-Src, c-Src(mt), in comparison with its wild-type protein, c-Src(wt), in the human non-transformed breast epithelial cell line MCF-10A.

The reverse transcriptase-RNase H: from viruses to antiviral defense.

Ubiquitous, reverse transcriptase may have contributed to the transition from the RNA to the DNA world, a transition that also involved RNase H-like activities. Both enzymes shaped various genomes and antiviral defense systems as endogenous retroviruses (ERVs) and transposable elements (TEs). A close relationship between a dozen components of retroviruses and the small interfering RNA (siRNA) antiviral-defense machinery has been characterized.

Small-molecule inhibitors of AF6 PDZ-mediated protein-protein interactions.

PDZ (PSD-95, Dlg, ZO-1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ-mediated protein-protein interactions has important implications in disease-related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development.