Levels ofα 1 in the spring and autumn seasons

Summary In a group of 84 pairs of 11-year-old children of both sexes, the level of the ₁-antitrypsin ( ₁-AT) were ascertained in the autumn and spring. Although the mean levels of ₁-AT in the two seasons hardly differed, the highly significant seasonal changes in the distribution curves of ₁-AT values were noted in boys, whereas the levels showed higher stability in girls.     

Studies on the thyroid in transgenic mice expressing the genes for human and bovine growth hormone

The thyroid glands of transgenic mice (TM) expressing the genes for human (h) and bovine (b) growth hormone (GH) were studied. The percentages of larger follicles in hGH TM of either sex were significantly greater than in the corresponding normal littermates, and follicles ranging up to 350 microns in diameter were present in male hGH TM. In contrast, thyroid follicles were only slightly enlarged in male bGH TM, and were unchanged in female bGH TM. The serum concentrations of T4 were significantly decreased in male bGH TM and not altered in the other groups. Serum concentrations of T3 were slightly, but significantly increased in female hGH TM and female bGH TM, but were unaffected in male TM of either type. Since the principal difference between these foreign GHs in rodents is the additional lactogenic activity of human GH, these results may indicate that the effects of prolactin can influence the development of the thyroid.     

Sleep inspires insight

Insight denotes a mental restructuring that leads to a sudden gain of explicit knowledge allowing qualitatively changed behaviour. Anecdotal reports on scientific discovery suggest that pivotal insights can be gained through sleep. Sleep consolidates recent memories and, concomitantly, could allow insight by changing their representational structure. Here we show a facilitating role of sleep in a process of insight. Subjects performed a cognitive task requiring the learning of stimulus-response sequences, in which they improved gradually by increasing response speed across task blocks. However, they could also improve abruptly after gaining insight into a hidden abstract rule underlying all sequences. Initial training establishing a task representation was followed by 8 h of nocturnal sleep, nocturnal wakefulness, or daytime wakefulness. At subsequent retesting, more than twice as many subjects gained insight into the hidden rule after sleep as after wakefulness, regardless of time of day. Sleep did not enhance insight in the absence of initial training. A characteristic antecedent of sleep-related insight was revealed in a slowing of reaction times across sleep. We conclude that sleep, by restructuring new memory representations, facilitates extraction of explicit knowledge and insightful behaviour.     

Conserved function for embryonic nodal cilia

How left right handedness originates in the body plan of the developing vertebrate embryo is a subject of considerable debate. In mice, a left right bias is thought to arise from a directional extracellular flow (nodal flow) that is generated by dynein-dependent rotation of monocilia on the ventral surface of the embryonic node. Here we show that the existence of node monocilia and the expression of a dynein gene that is implicated in ciliary function are conserved across a wide range of vertebrate classes, indicating that a similar ciliary mechanism may underlie the establishment of handedness in all vertebrates.     

Dynamic thiolation-thioesterase structure of a non-ribosomal peptide synthetase

Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) produce numerous secondary metabolites with various therapeutic/antibiotic properties. Like fatty acid synthases (FAS), these enzymes are organized in modular assembly lines in which each module, made of conserved domains, incorporates a given monomer unit into the growing chain. Knowledge about domain or module interactions may enable reengineering of this assembly line enzymatic organization and open avenues for the design of new bioactive compounds with improved therapeutic properties. So far, little structural information has been available on how the domains interact and communicate. This may be because of inherent interdomain mobility hindering crystallization, or because crystallized molecules may not represent the active domain orientations. In solution, the large size and internal dynamics of multidomain fragments (>35 kilodaltons) make structure determination by nuclear magnetic resonance a challenge and require advanced technologies. Here we present the solution structure of the apo-thiolation-thioesterase (T-TE) di-domain fragment of the Escherichia coli enterobactin synthetase EntF NRPS subunit. In the holoenzyme, the T domain carries the growing chain tethered to a 4'-phosphopantetheine whereas the TE domain catalyses hydrolysis and cyclization of the iron chelator enterobactin. The T-TE di-domain forms a compact but dynamic structure with a well-defined domain interface; the two active sites are at a suitable distance for substrate transfer from T to TE. We observe extensive interdomain and intradomain motions for well-defined regions and show that these are modulated by interactions with proteins that participate in the biosynthesis. The T-TE interaction described here provides a model for NRPS, PKS and FAS function in general as T-TE-like di-domains typically catalyse the last step in numerous assembly-line chain-termination machineries.