Chemopreventive compounds—View from the other side

Increasing attention is being paid to the possibility of applying chemopreventive agents for the protection of individuals from cancer risk. The beneficial potential of chemoprotective compounds is usually well documented by extensive experimental data. To assure the desired effect, these compounds are frequently concentrated to produce dietary supplements for human use. The additive and synergistic effects of other food constituents are, however, frequently ignored. Even natural chemopreventive compounds have to be considered as xenobiotics. Thus, as much attention has to be paid to their testing prior to their wide application as is usual in drug development for human treatment. Unfortunately, much of the research in this area is solely based on simplified in vitro systems that cannot take into account the complexity of biotransformation processes, e.g. chemopreventive compound-drug interaction, effect on metabolism of endogenic compounds. Hence, the predicted chemopreventive potential is not attained in respect of cancer prevention; moreover, the administration of high doses of chemopreventive compounds might be even detrimental for the human health.     

The other side of the coin: Hypersociability

Affiliative social motivation and behavior, that is, sociability that includes attachment, prosocial behavior (sharing, caring and helping) and empathy (the ability to understand and share the feelings of others), has high variability in the human population, with a portion of people outside of the normal range. While psychiatric disorders and autism spectrum disorders are typically associated with a deficit in social behavior, the opposite trait of hypersociability and indiscriminate friendliness are exhibited by individual with specific neurodevelopmental disorders and following early adverse care. Here we discuss both genetic and environmental factors that cause or increase the risk for developing pathological hypersociability from human to rodent models.     

The other side of molecular biology

The question is raised whether in addition to the well-known causal processes of molecular mechanics there are other effects of atomic physics which might appear significantly in biology. We find one, namely the process of molecular synthesis that involves ambiguities due to the competition of isomers. The ambiguities, mathematically called bifurcations, represent binary decisions buried in noise. The assumption is made that collectively there are enough causally undefined decisions to speak of the creativity of the organism as a basic phenomenon in its own right. Creativity, in the past a purely literary term, becomes then a scientific one for which exact definitions are required. We point out that in such a case theory can only specify necessary conditions of phenomena not sufficient ones, as distinct from physics. A very brief survey is made of the major features of a biological theory based on such assumptions.     

Tissue-based class control: the other side of tolerance

In this Essay, we offer a new perspective on how immune responses are regulated. We do not cover how they are turned on and off, but focus instead on the second major aspect of an immune response: the control of effector class. Although it is generally thought that the class of an immune response is tailored to fit the invading pathogen, we suggest here that it is primarily tailored to fit the tissue in which the response occurs. To this end, we cover such topics as the nature of T helper (T(H)) cell subsets (current and yet to be discovered), the nature of privileged sites, the difference between oral tolerance and oral vaccination, why the route of immunization matters, whether the T(H)1-type response is really the immune system's primary defense, and whether there might be a different role for some regulatory T cells.     

Cell-penetrating peptides: breaking through to the other side

Cell-penetrating peptides (CPPs) have been previously shown to be powerful transport vector tools for the intracellular delivery of a large variety of cargoes through the cell membrane. Intracellular delivery of plasmid DNA (pDNA), oligonucleotides, small interfering RNAs (siRNAs), proteins and peptides, contrast agents, drugs, as well as various nanoparticulate pharmaceutical carriers (e.g., liposomes, micelles) has been demonstrated both in vitro and in vivo. This review focuses on the peptide-based strategy for intracellular delivery of CPP-modified nanocarriers to deliver small molecule drugs or DNA. In addition, we discuss the rationales for the design of 'smart' pharmaceutical nanocarriers in which the cell-penetrating properties are hidden until triggered by exposure to appropriate environmental conditions (e.g., a particular pH, temperature, or enzyme level), applied local microwave, ultrasound, or radiofrequency radiation.     

Making a membrane on the other side of the wall

The outer membrane (OM) of Gram-negative bacteria is positioned at the frontline of the cell's interaction with its environment and provides a barrier against influx of external toxins while still allowing import of nutrients and excretion of wastes. It is a remarkable asymmetric bilayer with a glycolipid surface-exposed leaflet and a glycerophospholipid inner leaflet. Lipid asymmetry is key to OM barrier function and several different systems actively maintain this lipid asymmetry. All OM components are synthesized in the cytosol before being secreted and assembled into a contiguous membrane on the other side of the cell wall. Work in recent years has uncovered the pathways that transport and assemble most of the OM components. However, our understanding of how phospholipids are delivered to the OM remains notably limited. Here we will review seminal works in phospholipid transfer performed some 40 years ago and place more recent insights in their context. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.