A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

Advances in anti-viral immune defence: revealing the importance of the IFN JAK/STAT pathway

Interferon-alpha (IFN-α) is a potent anti-viral cytokine, critical to the host immune response against viruses. IFN-α is first produced upon viral detection by pathogen recognition receptors. Following its expression, IFN-α embarks upon a complex downstream signalling cascade called the JAK/STAT pathway. This signalling pathway results in the expression of hundreds of effector genes known as interferon stimulated genes (ISGs). These genes are the basis for an elaborate effector mechanism and ultimately, the clearance of viral infection. ISGs mark an elegant mechanism of anti-viral host defence that warrants renewed research focus in our global efforts to treat existing and emerging viruses. By understanding the mechanistic role of individual ISGs we anticipate the discovery of a new “treasure trove” of anti-viral mediators that may pave the way for more effective, targeted and less toxic anti-viral therapies. Therefore, with the aim of highlighting the value of the innate type 1 IFN response in our battle against viral infection, this review outlines both historic and recent advances in understanding the IFN-α JAK/STAT pathway, with a focus on new research discoveries relating to specific ISGs and their potential role in curing existing and future emergent viral infections.     

Numerous potentially functional but non-genic conserved sequences on human chromosome 21

The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.     

Synthesis of a structure proposed for scotophobin

Zusammenfassung Es wurde ein biologisch interessantes Polypeptid mit der für Scotophobin vorgeschlagenen Sequenz synthetisiert. Da dieses nur eine geringe biologische Aktivität besass, wird angenommen, dass die für das natürliche Produkt vorgeschlagene Strukturformel nicht korrekt ist.

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We thank the National Institutes of Health (MH 19320) for the support of this work.     

Impact frustration of the origin of life

One possible definition for the origin of life on Earth is the time at which the interval between devastating environmental insults by impact exceeded the timescale for establishing self-replicating proto-organisms. A quantitative relationship for the Hadean (pre-3,800 Myr ago) and Early Archean (3,800 to 3,400 Myr) impact flux can be derived from the lunar and terrestrial impact records. Also, the effects of impact-related processes on the various environments proposed for abiogenesis (the development of life through chemical evolution from inorganic materials) can be estimated. Using a range of plausible values for the timescale for abiogenesis, the interval in time when life might first have bootstrapped itself into existence can be found for each environment. We find that if the deep marine hydrothermal setting provided a suitable site, abiogenesis could have happened as early as 4,000 to 4,200 Myr ago, whereas at the surface of the Earth abiogenesis could have occurred between 3,700 and 4,000 Myr.