New and Exciting in PLoS this week

So, let's see what's new in PLoS Genetics, PLoS Computational Biology and PLoS Pathogens this week. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. Here are my own picks for the week - you go and look for your own favourites:

Abnormal Brain Iron Homeostasis in Human and Animal Prion Disorders:

Prion disorders are neurodegenerative conditions of humans and animals that are invariably fatal. The main agent responsible for neurotoxicity in all prion disorders is PrP-scrapie (PrPSc), a β-sheet rich isoform of a normal cell-surface glycoprotein, the prion protein (PrPC). Deposits of PrPSc in the brain parenchyma are believed to induce neurotoxicity, though the underlying mechanisms are not entirely clear. Emerging evidence from prion-infected cell and mouse models implicates redox-iron in prion disease-associated neurotoxicity. However, a systematic evaluation of iron homeostasis in prion disease-affected brains and the underlying mechanism of iron dyshomeostasis are lacking. In this report, we demonstrate that prion disease-affected human, mouse, and hamster brains exhibit a state of iron deficiency in the presence of excess total brain iron, resulting in a state of iron imbalance. The underlying cause of this phenotype is likely sequestration of iron in cellular ferritin that becomes detergent-insoluble, possibly due to association with PrPSc. This results in a state of iron bio-insufficiency, leading to increased iron uptake by the cells and worsening of the state of iron imbalance. Since iron is highly toxic if mismanaged, these results implicate iron imbalance as a significant contributing factor in prion disease-associated neurotoxicity.

Genome-Wide Association Analyses Identify SPOCK as a Key Novel Gene Underlying Age at Menarche:

Menarche is a physical milestone in a woman's life. Age at menarche (AAM) is related to many common female health problems. AAM is mainly determined by genetic factors. However, the specific genes and the associated mechanisms underlying AAM are largely unknown. Here, taking advantage of the most recent technological advances in the field of human genetics, we identified multiple genetic variants in a gene, SPOCK, which are associated with AAM variation in a group of Caucasian women. This association was subsequently confirmed not only in two independent groups of Caucasian women but also across ethnic boundaries in one group of Chinese women. In addition, SPOCK has a function in regulating a key factor involved in menstrual cycles, MMP-2, which provides further support to our findings. Our study provides a solid basis for further investigation of the gene, which may help to reveal the underlying mechanisms for the timing of menarche and for AAM's relationship with women's health in general.

Life, Death, Differentiation, and the Multicellularity of Bacteria:

In recent years, bacterial geneticists and microbiologists have begun moving away from the view that the clonal cell populations they study in the lab are homogeneous lots of identical, autonomous individuals and toward one that was suggested decades ago [1], in which social and even multicellular attributes of bacteria are recognized. Bacterial clones display differentiation, development, cell-cell communication, aging, and even apparent apoptosis, and not just the species with visually appreciable phase variations of surface proteins, spore formation, or variation between swimming and sessile cell types. These features appear to be ubiquitous, applying even to Escherichia coli, which has been long regarded as a laboratory model for producing homogeneous cell clones.

A Human Protein Interaction Network Shows Conservation of Aging Processes between Human and Invertebrate Species:

Studies of longevity in model organisms such as baker's yeast, roundworm, and fruit fly have clearly demonstrated that a diverse array of genetic mutations can result in increased life span. In fact, large-scale genetic screens have identified hundreds of genes that when mutated, knocked down, or deleted will significantly enhance longevity in these organisms. Despite great progress in understanding genetic and genomic determinants of life span in model organisms, the general relevance of invertebrate longevity genes to human aging and longevity has yet to be fully established. In this study, we show that human homologs of invertebrate longevity genes change in their expression levels during aging in human tissue. We also show that human genes encoding proteins that interact with human longevity homolog proteins are also changed in expression during human aging. These observations taken together indicate that the broad patterns underlying genetic control of life span in invertebrates is highly relevant to human aging and longevity. We also present a collection of novel candidate genes and proteins that may influence human life span.