Aquaporins: Another piece in the osmotic puzzle

Osmolarity not only plays a key role in cellular homeostasis but also challenges cell survival. The molecular understanding of osmosis has not yet been completely achieved, and the discovery of aquaporins as molecular entities involved in water transport has caused osmosis to again become a focus of research. The main questions that need to be answered are the mechanism underlying the osmotic permeability coefficients and the extent to which aquaporins change our understanding of osmosis. Here, attempts to answer these questions are discussed. Critical aspects of the state of the state of knowledge on osmosis, a topic that has been studied since 19th century, are reviewed and integrated with the available information provided by in vivo, in vitro and in silico approaches.     

Apolipoprotein E: a major piece in the Alzheimer's disease puzzle

Alzheimer's disease (AD) is a complex neurodegenerative disorder with multiple etiologies. The presence of the E4 isoform of apolipoprotein E (apoE) has been shown to increase the risk and to decrease the age of onset for AD and is the major susceptibility factor known for the disease. ApoE4 has been shown to intensify all the biochemical distrubances characteristic of AD, including beta amyloid (Aβ) deposition, tangle formation, neuronal cell death, oxidative stress, synaptic plasticity and dysfunctions of lipid homeostasis and cholinergic signalling. In contrast, other apoE isoforms are protective. Here we review and discuss these major hypotheses of the apoE4-AD association.     

Somatic Hypermutation: Another piece in the hypermutation puzzle

Studies with transgenic mice are beginning to define the minimal requirements for the somatic hypermutation of immunoglobulin genes that is critical in the production of high-affinity antibodies.     

Motor learning: the FoxP2 puzzle piece

Mutation of the DNA-binding region of the FOXP2 protein causes an inherited language disorder. A recent study provides the first data on mice with this mutation, which exhibit deficits in motor-skill learning and abnormal properties of neural circuits that contribute to these skills.     

The 19S cap puzzle: a new jigsaw piece

After elucidation of the atomic details of 20S proteasomes, current research focuses on the regulatory 19S particle. In this issue of Structure, He et?al. present the crystal structure of Rpn2 and use electron microscopy to examine differences between Rpn2 and Rpn1.     

Hominization in the rainforest: The chimpanzee's piece of the puzzle

Many models of human evolution propose that key behavioral innovations were involved in the divergence of the human line from the ape line. An ecological reason, the shift from dense forests to a more open habitat, is suggested as the basis for these innovations. Primate models can be useful to our understanding of how environmental factors can affect such key behaviors. New results on forest chimpanzees demonstrate that for most patterns of behavior considered to favor a savanna model, the environmental influences are in opposition to the expectations. A new evaluation of the environmental influences on human evolution is required. We propose that either patterns of key human behaviors were inaccurately distinguished or that the hominization process started while the common ancestor of the chimpanzee and man was alive.     

Capturing VCP: another molecular piece in the ALS jigsaw puzzle

TDP-43 mislocalization and aggregation are implicated in the pathogenesis of ALS and FTLD-U. Valosin containing protein (VCP) mutations also lead to TDP-43 deposition, resulting in Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). In this issue of Neuron, Johnson et?al. used whole-exome capture to identify VCP mutations in familial ALS. This extends the VCP phenotype to include motor neuron degeneration and provides another molecular tool to explore neurodegeneration disease mechanisms underlying the TDP-43 proteinopathies.