Catálogo de publicaciones - revistas

<jats:title>Generating homozygous mutations</jats:title> <jats:p>Loss-of-function mutations may only produce a mutant phenotype when both copies of the gene are mutated. Gantz and Bier developed a method they call mutagenic chain reaction (MCR) that autocatalytically produces homozygous mutations. MCR uses the initial mutated allele to cause a mutation in the allele on the opposing chromosome and thus the homozygosity of the trait. MCR technology could have broad applications in diverse organisms.</jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. 442 </jats:p>

<jats:title>Ribosomes help careful protein folding</jats:title> <jats:p> Protein assembly in vitro is useful for studying small molecules but is problematic for studying the assembly of larger, more complex proteins. Kim <jats:italic>et al.</jats:italic> analyzed the biogenesis of the mutation-prone nucleotide-binding domain of the cystic fibrosis conductance regulator (CFTR) (see the Perspective by Puglisi). Newly synthesized polypeptides emerged relatively slowly from the ribosome and folded through a modulated pathway that ensured correct protein folding. Some parts of the protein chain folded immediately upon synthesis, whereas other segments did so more slowly. It appears that acquiring the correct conformation for this complex protein is partly guided by the ribosome itself. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. 444; see also p. 399 </jats:p>

<jats:title>A genetic cause for severe influenza</jats:title> <jats:p> Although chicken soup and plenty of rest get most kids through an influenza virus infection, some require hospitalization. Ciancanelli <jats:italic>et al.</jats:italic> report on one child who suffered severely from influenza because of null mutations in the gene for transcription factor IRF7. Cells isolated from this patient could not make enough secreted antiviral proteins, called interferons, to halt viral replication. The requirement for IRF7 seems quite specific, because this patient recovers normally from other common childhood viral infections. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. 448 </jats:p>

<jats:title>SARM1-driven axon degeneration</jats:title> <jats:p> Axons, the long protrusions of nerve cells, are programmed to self-destruct under certain conditions that occur during development, stress, or disease states. Gerdts <jats:italic>et al.</jats:italic> outline a biochemical mechanism that controls such axon degeneration. The authors designed versions of SARM1 (sterile alpha and TIR motif—constraining 1) that could be activated or inhibited in cells. Their experiments showed that the activation of SARM1 was necessary and sufficient to cause axon destruction in cultured mouse neurons. SARM1-mediated destruction was associated with depletion of the metabolic cofactor NAD <jats:sup>+</jats:sup> from cells. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. 453 </jats:p>

<jats:title>Force to unblock a clogged ribosome</jats:title> <jats:p> The synthesis of proteins from mRNA by the ribosome is highly regulated. But newly synthesized protein chains can still block the ribosome exit tunnel and slow protein synthesis. Goldman <jats:italic>et al.</jats:italic> use optical tweezers to show that by pulling on the stuck protein chain, they can unblock a clogged exit tunnel (see the Perspective by Puglisi). In vivo, the folding of a nascent protein chain just outside the tunnel also generates enough force to unclog a block, indicating that ribosome-peptide interactions fine-tune protein synthesis. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. 457; see also p. 399 </jats:p>

<jats:p>Protein-based assays are essential tools for many laboratories in both industrial and academic settings. Protein targets of interest are often found at low abundance and can be complex in nature, making their analysis intractable. One of the considerable challenges when developing assays is that small sample sizes can limit the amount of relevant information that can be extracted. The ability to miniaturize an assay allows sufficient data to be collected from scarce samples, while being able to interrogate multiple proteins simultaneously through multiplexing enables researchers to extract more data from each experiment and improve the biological relevance of the results significantly. This multiplexing ability provides the opportunity to quantitatively profile multiple signaling pathways from minute samples derived from very small cell populations. Furthermore, having the tools to directly study protein target binding in cells allows biologically relevant information to be preserved, including subcellular localization, posttranslational modifications, and the occurrence of multiple interactions with different accessory proteins and other scaffolding molecules. In this webinar, two examples of such approaches will be discussed. The first is the use of a method to amplify the signal in a target engagement assay using small samples, utilized to interrogate modulators of cytokine secretion. The second involves a so-called cellular thermal shift assay (CETSA) to detect protein-ligand interactions without the need to modify either the ligand or receptor, or the necessity for recombinant cell lines.</jats:p>

<jats:p>On this week's show: The 25th Anniversary of the Hubble Space Telecope, and a roundup of daily news stories.</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>