Comparison of the time courses of luteinizing hormone (LH) secretion rates during continuous stimulation by LH-releasing hormone (LH-RH) in vivo and in vitro

Summary The patterns of LH secretion during constant stimulation of the pituitary glands of estradiol-treated ovariectomized rats with a maximally stimulating amount of LH-RH in vivo and in vitro correspond with each other qualitatively and quantitatively. In vitro the changes with time of the LH secretion rate are somewhat retarded, especially the occurrence of desensitization.     

Comparison of the time courses of luteinizing hormone (LH) secretion rates during continuous stimulation by LH-releasing hormone (LH-RH) in vivo and in vitro

The patterns of LH secretion during constant stimulation of the pituitary glands of estradiol-treated ovariectomized rats with a maximally stimulating amount of LH-RH in vivo and in vitro correspond with each other qualitatively and quantitatively. In vitro the changes with time of the LH secretion rate are somewhat retarded, especially the occurrence of desensitization.     

Single-substrate liquid-crystal displays by photo-enforced stratification

Data visualization plays a crucial role in our society, as illustrated by the many displays that surround us. In the future, displays may become even more pervasive, ranging from individually addressable image-rendering wall hangings to data displays integrated in clothes. Liquid-crystal displays (LCDs) provide most of the flat-panel displays currently used. To keep pace with the ever-increasing possibilities afforded by developments in information technology, we need to develop manufacturing processes that will make LCDs cheaper and larger, with more freedom in design. Existing batch processes for making and filling LCD cells are relatively expensive, with size and shape limitations. Here we report a cost-effective, single-substrate technique in which a coated film is transformed into a polymer-covered liquid-crystal layer. This approach is based on photo-enforced stratification: a two-step photopolymerization-induced phase separation of a liquid-crystal blend and a polymer precursor. The process leads to the formation of micrometre-sized containers filled with a switchable liquid-crystal phase. In this way, displays can be produced on a variety of substrates using current coating technology. The developed process may be an important step towards new technologies such as 'display-on-anything' and 'paintable displays'.     

Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human

Linkage analysis and haplotype mapping in interspecific mouse crosses (Mus musculus x Mus spretus) identified the gene encoding Aurora2 (Stk6 in mouse and STK15 in human) as a candidate skin tumor susceptibility gene. The Stk6 allele inherited from the susceptible M. musculus parent was overexpressed in normal cells and preferentially amplified in tumor cells from F(1) hybrid mice. We identified a common genetic variant in STK15 (resulting in the amino acid substitution F31I) that is preferentially amplified and associated with the degree of aneuploidy in human colon tumors. The Ile31 variant transforms rat1 cells more potently than the more common Phe31 variant. The E2 ubiquitin-conjugating enzyme UBE2N was a preferential binding partner of the 'weak' STK15 Phe31 variant form in yeast two-hybrid screens and in human cells. This interaction results in colocalization of UBE2N with STK15 at the centrosomes during mitosis. These results are consistent with an important role for the Ile31 variant of STK15 in human cancer susceptibility.     

Social parasitism by male-producing reproductive workers in a eusocial insect

The evolution of extreme cooperation, as found in eusocial insects (those with a worker caste), is potentially undermined by selfish reproduction among group members. In some eusocial Hymenoptera (ants, bees and wasps), workers can produce male offspring from unfertilized eggs. Kin selection theory predicts levels of worker reproduction as a function of the relatedness structure of the workers' natal colony and the colony-level costs of worker reproduction. However, the theory has been only partially successful in explaining levels of worker reproduction. Here we show that workers of a eusocial bumble bee (Bombus terrestris) enter unrelated, conspecific colonies in which they then produce adult male offspring, and that such socially parasitic workers reproduce earlier and are significantly more reproductive and aggressive than resident workers that reproduce within their own colonies. Explaining levels of worker reproduction, and hence the potential of worker selfishness to undermine the evolution of cooperation, will therefore require more than simply a consideration of the kin-selected interests of resident workers. It will also require knowledge of the full set of reproductive options available to workers, including intraspecific social parasitism.     

Structure of the E. coli signal recognition particle bound to a translating ribosome

The prokaryotic signal recognition particle (SRP) targets membrane proteins into the inner membrane. It binds translating ribosomes and screens the emerging nascent chain for a hydrophobic signal sequence, such as the transmembrane helix of inner membrane proteins. If such a sequence emerges, the SRP binds tightly, allowing the SRP receptor to lock on. This assembly delivers the ribosome-nascent chain complex to the protein translocation machinery in the membrane. Using cryo-electron microscopy and single-particle reconstruction, we obtained a 16 A structure of the Escherichia coli SRP in complex with a translating E. coli ribosome containing a nascent chain with a transmembrane helix anchor. We also obtained structural information on the SRP bound to an empty E. coli ribosome. The latter might share characteristics with a scanning SRP complex, whereas the former represents the next step: the targeting complex ready for receptor binding. High-resolution structures of the bacterial ribosome and of the bacterial SRP components are available, and their fitting explains our electron microscopic density. The structures reveal the regions that are involved in complex formation, provide insight into the conformation of the SRP on the ribosome and indicate the conformational changes that accompany high-affinity SRP binding to ribosome nascent chain complexes upon recognition of the signal sequence.     

Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome.

Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS; MIM 260920) is an autosomal recessive disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash. Diagnostic hallmark of HIDS is a constitutively elevated level of serum immunoglobulin D (IgD), although patients have been reported with normal IgD levels. To determine the underlying defect in HIDS, we analysed urine of several patients and discovered increased concentrations of mevalonic acid during severe episodes of fever, but not between crises. Subsequent analysis of cells from four unrelated HIDS patients revealed reduced activities of mevalonate kinase (MK; encoded by the gene MVK), a key enzyme of isoprenoid biosynthesis. Sequence analysis of MVK cDNA from the patients identified three different mutations, one of which was common to all patients. Expression of the mutant cDNAs in Escherichia coli showed that all three mutations affect the activity of the encoded proteins. Moreover, immunoblot analysis demonstrated a deficiency of MK protein in patient fibroblasts, indicating a protein-destabilizing effect of the mutations.     

Specific recognition of staphylococcal enterotoxin A by human T cells bearing receptors with the V gamma 9 region

T cells bearing the alpha beta receptor can specifically react with target cells coated with staphylococcal enterotoxin and expressing major histocompatibility complex class II molecules; these responses depend on which variable region (V) of the receptor's beta-subunit is used. We have now examined whether a similar situation exists for human T cells bearing the gamma delta receptor. We found that reactivity to staphylococcal enterotoxin A is strictly dependent on the presence of the V gamma 9 variable region in the gamma delta T-cell receptor (TCR). These cytotoxic responses required the expression of HLA class II molecules by the target cell and could be inhibited by anti-gamma delta TCR and by anti-HLA-class-II monoclonal antibodies. In contrast to alpha beta TCR+ cell clones, no proliferative response of V gamma 9+ T-cell clones towards stimulator cells coated with enterotoxin A was observed in vitro. These results indicate that the gamma delta TCR repertoire might be influenced by enterotoxin A produced during staphylococcal infections in vivo. This could provide a molecular basis for the observation that V gamma 9+ T cells form the large majority of peripheral gamma delta TCR+ cells but only a small proportion of thymic gamma delta TCR+ cells.