Lifeboat Foundation

Background: Breast cancer is the most common form of cancer in women worldwide. Advances in the early diagnosis and treatment of cancer in the last decade have progressively decreased the cancer mortality rate, and in recent years, immunotherapy has emerged as a relevant tool against cancer. HER2+ and triple-negative breast cancers (TNBCs) are considered more immunogenic and suitable for this kind of treatment due to the higher rate of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression. In TNBC, genetic aberrations further favor immunogenicity due to more neo-antigens in cancer cells. Methods: This review summarizes the principal ongoing conventional and investigational immunotherapies in breast cancer. Particularly, immune checkpoint inhibitors (ICIs) and their use alone or combined with DNA damage repair inhibitors (DDRis) are described.

In a recent study published in the journal Eurosurveillance, researchers examine antibiotic resistance genes (ARGs) and their mobility in Bifidobacteriales and Lactobacillales species through the use of a unified bioinformatic pipeline to isolate these bacteria from food and probiotic sources.

Study: A survey on antimicrobial resistance genes of frequently used probiotic bacteria, 1901 to 2022. Image Credit: MilletStudio / Shutterstock.com.

Identifying potential sources of AMR is important, as it is one of the key threats to the treatment of multiple communicable diseases worldwide in both humans and animals. Excessive antimicrobial use (AMU) has contributed to a surge in AMR rates worldwide; however, despite mitigation measures to decrease AMU, excessive antibiotic use by animals and humans remains a common practice in many nations.

More than 37 million American adults are living with kidney disease and most don’t know it. “There are a number of physical signs of kidney disease, but sometimes people attribute them to other conditions. Also, those with kidney disease tend not to experience symptoms until the very late stages, when the kidneys are failing or when there are large amounts of protein in the urine. This is one of the reasons why only 10% of people with chronic kidney disease know that they have it,” says Dr. Joseph Vassalotti, Chief Medical Officer at the National Kidney Foundation.

While the only way to know for sure if you have kidney disease is to get tested, Dr. Vassalotti shares 10 possible signs you may have kidney disease. If you’re at risk for kidney disease due to high blood pressure, diabetes, a family history of kidney failure or if you’re older than age 60, it’s important to get tested annually for kidney disease. Be sure to mention any symptoms you’re experiencing to your healthcare practitioner.

What is antibiotic resistance? What is the global clinical antibacterial pipeline? What is the global preclinical antibacterial pipeline? Institutions associated with preclinical drug development Preclinical projects Trends in the preclinical antibacterial pipeline References Further reading.

The global preclinical antibacterial pipeline refers to innovative antibacterial candidate drugs that are under development with the aim of effectively eliminating newly emerged and pre-existing priority pathogens.

Antibacterial medicines or antibiotics treat bacterial infections in humans, animals, and plants. However, bacteria may eventually develop resistance against antibiotics-mediated killing by acquiring genetic mutations. Although antibiotic resistance occurs naturally, misuse or overuse of antibiotics can significantly escalate the process.

Many cancer therapies do not produce the hoped-for results. A common reason for this is that the tumors develop resistance to the medications. This is the case, for example, with alpelisib, a drug that has been approved for use in Switzerland for the past few years as a treatment for advanced breast cancer.

A research group at the Department of Biomedicine of the University of Basel has now discovered that the loss of the neurofibromin 1 (NF1) gene leads to a reduced response to alpelisib. The researchers also found that the dietary supplement N-acetylcysteine restores the sensitivity of cancer cells to this treatment. The findings have been published in the journal Cell Reports Medicine on April 11.

At the moment, patients with advanced and metastatic breast cancer lack effective treatment options. The PI3K signaling pathway is often overactive in breast cancer due to mutations promoting tumor development. The approval of the PI3K inhibitor Alpelisib was therefore keenly anticipated.

The remarkable physicochemical properties of the natural nucleic acids, DNA and RNA, define modern biology at the molecular level and are widely believed to have been central to life’s origins. However, their ability to form repositories of information as well as functional structures such as ligands (aptamers) and catalysts (ribozymes/DNAzymes) is not unique. A range of nonnatural alternatives, collectively termed xeno nucleic acids (XNAs), are also capable of supporting genetic information storage and propagation as well as evolution. This gives rise to a new field of “synthetic genetics,” which seeks to expand the nucleic acid chemical toolbox for applications in both biotechnology and molecular medicine. In this review, we outline XNA polymerase and reverse transcriptase engineering as a key enabling technology and summarize the application of “synthetic genetics” to the development of aptamers, enzymes, and nanostructures.

Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.

Macromolecular information transfer can be defined as the process by which a coded monomer sequence is communicated from one macromolecule to another. In such a transfer process, the information sequence can be kept identical, transformed into a complementary sequence or even translated into a different molecular language. Such mechanisms are crucial in biology and take place in DNA→DNA replication, DNA→RNA transcription and RNA→protein translation. In fact, there would be no life on Earth without macromolecular information transfer. Mimicking such processes with synthetic macromolecules would also be of major scientific relevance because it would open up new avenues for technological applications (e.g. data storage and processing) but also for the creation of artificial life. In this important context, this minireview summarizes recent research about information transfer in synthetic oligomers and polymers. Medium-and long-term perspectives are also discussed.

Keywords: Artificial Translation; Molecular Replication; Precision Polymers; Sequence-Controlled Polymers; Template-Directed Synthesis.

© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

How life emerged from simple non-life chemicals on the ancient Earth is one of the greatest mysteries in biology. The gene expression system of extant life is based on the interdependence between multiple molecular species (DNA, RNA, and proteins). While DNA is mainly used as genetic material and proteins as functional molecules in modern biology, RNA serves as both genetic material and enzymes (ribozymes). Thus, the evolution of life may have begun with the birth of a ribozyme that replicated itself (the RNA world hypothesis), and proteins and DNA joined later. However, the complete self-replication of ribozymes from monomeric substrates has not yet been demonstrated experimentally, due to their limited activity and stability. In contrast, peptides are more chemically stable and are considered to have existed on the ancient Earth, leading to the hypothesis of RNA-peptide co-evolution from the very beginning. Our group and collaborators recently demonstrated that peptides with both hydrophobic and cationic moieties (e.g., KKVVVVVV) form β-amyloid aggregates that adsorb RNA and enhance RNA synthesis by an artificial RNA polymerase ribozyme and a simple peptide with only seven amino acid types (especially rich in valine and lysine) can fold into the ancient β-barrel conserved in various enzymes, including the core of cellular RNA polymerases. These findings, together with recent reports from other groups, suggest that simple prebiotic peptides could have supported the ancient RNA-based replication system, gradually folded into RNA-binding proteins, and eventually evolved into complex proteins like RNA polymerase.

Keywords: RNA world; ancient proteins; central dogma; origin of life; peptide.

© 2023 Japanese Society of Developmental Biologists.

Individual RNA remains a challenging signal to synthetically transduce into different types of cellular information. Here, we describe Ribozyme-ENabled Detection of RNA (RENDR), a plug-and-play strategy that uses cellular transcripts to template the assembly of split ribozymes, triggering splicing reactions that generate orthogonal protein outputs. To identify split ribozymes that require templating for splicing, we use laboratory evolution to evaluate the activities of different split variants of the Tetrahymena thermophila ribozyme. The best design delivers a 93-fold dynamic range of splicing with RENDR controlling fluorescent protein production in response to an RNA input. We further resolve a thermodynamic model to guide RENDR design, show how input signals can be transduced into diverse outputs, demonstrate portability across different bacteria, and use RENDR to detect antibiotic-resistant bacteria. This work shows how transcriptional signals can be monitored in situ and converted into different types of biochemical information using RNA synthetic biology.

© 2023. The Author(s).

Conflict of interest statement.