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.     

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.     

Theca interna: the other side of bovine follicular atresia

Currently, histological classifications of ovarian follicular atresia are almost exclusively based on the morphology of the membrana granulosa without reference to the theca interna. Atresia in the bovine small antral ovarian follicle has been redefined into antral or basal atresia where cell death commences initially within antral or basal regions of the membrana granulosa, respectively. To examine cell death in the theca interna in the two types of atretic follicles, bovine ovaries were collected and processed for immunohistochemistry and light microscopy. Follicles were classified as healthy, antral atretic, or basal atretic. Follicle diameter was recorded and sections stained with lectin from Bandeiraea simplicifolia to identify endothelial cells or with an antibody to cytochrome P450 cholesterol side-chain cleavage to identify steroidogenic cells and combined with TUNEL labeling to identify dead cells. The numerical density of steroidogenic cells within the theca interna was significantly reduced (P < 0.001) in basal atretic follicles in comparison with other follicles. Cell death was greater in both endothelial cells (P < 0.05) and steroidogenic cells (P < 0.01) of the theca interna of basal atretic follicles compared with healthy and antral atretic follicles. Thus, we conclude that the theca interna is susceptible to cell death early in atresia, particularly in basal atretic follicles.     

FLC or not FLC: the other side of vernalization

Vernalization is the promotion of the competence for floweringby long periods of low temperatures such as those typicallyexperienced during winters. In Arabidopsis, the vernalizationresponse is, to a large extent, mediated by the repression ofthe floral repressor FLC, and the stable epigenetic silencingof FLC after cold treatments is essential for vernalization.In addition to FLC, other vernalization targets exist in Arabidopsis.In grasses, vernalization seems to be entirely independent ofFLC. Here, the current understanding of FLC-independent branchesof the vernalization pathway in Arabidopsis and vernalizationwithout FLC in grasses is discussed. This review focuses onthe role of AGL19, AGL24, and the MAF genes in Arabidopsis.Interestingly, vernalization acts through related molecularmachineries on distinct targets. In particular, protein complexessimilar to Drosophila Polycomb Repressive Complex 2 play a prominentrole in establishing an epigenetic cellular memory for cold-regulatedexpression states of AGL19 and FLC. Finally, the similar networktopology of the apparently independently evolved vernalizationpathways of grasses and Arabidopsis is discussed. Key words: AGL19, Arabidopsis, chromatin, epigenetics, FLC, flowering time, polycomb, PRC2, vernalization Received 19 December 2007; Revised 11 February 2008 Accepted 15 February 2008     

The other side of the orexins: endocrine and metabolic actions

Although it is clear that the orexin/hypocretin peptides have a significant, physiologically relevant role in sleep/wakefulness, a broader picture has emerged indicating metabolic actions that may depend upon both neural and endocrine mechanisms for their manifestation. The ability of exogenous peptide to activate sympathetic tone, increase locomotor activity, and alter feeding behavior, together with the observed alterations in those functions in knockout animals, strongly suggests important neural actions of the endogenous orexins/hypocretins. Likewise, the action of exogenously administered peptides to alter endocrine function, in particular corticotropin release, has now been mirrored by potential endocrinopathies in knockout animals. Thus these pluripotent peptides hold great potential not only for the treatment of human narcolepsy but also to provide insight into the coordinated regulation of multiple physiological systems.     

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.