Collaborative signaling by mixed chemoreceptor teams in Escherichia coli

Chemoreceptors of the methyl-accepting chemotaxis protein family form clusters, typically at the cell pole(s), in both Bacteria and Archaea. To elucidate the architecture and signaling role of receptor clusters, we investigated interactions between the serine (Tsr) and aspartate (Tar) chemoreceptors in Escherichia coli by constructing Tsr mutations at the six hydrophobic and five polar residues implicated in "trimer of dimers" formation. Tsr mutants with proline replacements could not mediate serine chemotaxis, receptor clustering, or clockwise flagellar rotation. Alanine and tryptophan mutants, although also nonchemotactic, formed receptor clusters, and some produced clockwise flagellar rotation, indicating receptor-coupled activation of the signaling CheA kinase. The alanine and tryptophan mutants evidently assemble defective receptor complexes that cannot modulate CheA activity in response to serine stimuli. In cells containing wild-type Tar receptors, tryptophan replacements in Tsr interfered with Tar function, whereas four Tsr mutants with alanine replacements regained Tsr function. These epistatic and rescuable phenotypes imply interactions between Tsr and Tar dimers in higher-order signaling teams. The bulky side chain in tryptophan mutants may prevent stimulus-induced conformational changes in the team, whereas the small side chain in alanine mutants may permit signaling control when teamed with functional receptor molecules. Direct physical interactions between Tsr and Tar molecules were observed by in vivo chemical crosslinking. Wild-type Tsr crosslinked to Tar, whereas a clustering-defective proline replacement mutant did not. These findings indicate that bacterial chemoreceptor clusters are comprised of signaling teams, seemingly based on trimers of dimers, that can contain different receptor types acting collaboratively.     

Posttranslational processing of methyl-accepting chemotaxis proteins in Escherichia coli

Methyl-accepting chemotaxis proteins (MCPs) of Escherichia coli undergo changes in methylation state in response to chemical stimuli. The addition of methyl groups to MCP is dependent on cheR function; their removal is dependent on cheB function. This MCP methylation system is instrumental in establishing the unstimulated swimming pattern of E. coli and in enabling the cell to carry out sensory adaptation after a chemotactic response. We employed electrophoresis in sodium dodecyl sulfate-containing polyacrylamide gels to analyze MCP molecules synthesized in cheR deletion mutants lacking MCP-specific methyltransferase activity. MCP made under these conditions proved to be completely devoid of methyl groups. In the absence of cheB function as well, this unmethylated MCP is made in a form, designated 2^*, that exhibits several properties characteristic of methylated MCP. In the presence of cheB function, MCP 2^* is processed to a form, designated 1^*, that no longer resembles methylated MCP. The rate of this conversion process is modulated by chemotactic stimuli. Both MCP 1^* and MCP 2^* are capable of initiating changes in flagellar rotation in response to stimuli, and, in the presence of cheR function, both forms can accept methyl groups. We suggest that MCP 2^* is a normal intermediate in MCP synthesis in which one or more of the methyl-accepting glutamic acid residues carry a methyl-ester-like modification, which, like glutamic acid methyl esters, can be removed by cheB function. This cheB-dependent processing event does not appear to be reversible, but nevertheless it may play an important role in modulating the signaling behavior of newly synthesized MCP molecules.     

Perspectives on hand function in girls and women with Rett syndrome

Objective: Rett syndrome is a rare neurodevelopmental disorder that is usually associated with a mutation on the X-linked MECP2 gene. Hand function is particularly affected and we discuss theoretical and practical perspectives for optimising hand function in Rett syndrome.

Methods: We reviewed the literature pertaining to hand function and stereotypies in Rett syndrome and developed a toolkit for their assessment and treatment.

Results: There is little published information on management of hand function in Rett syndrome. We suggest assessment and treatment strategies based on available literature, clinical experience and grounded in theories of motor control and motor learning.

Conclusion: Additional studies are needed to determine the best treatments for hand function in Rett syndrome. Meanwhile, clinical needs can be addressed by supplementing the evidence base with an understanding of the complexities of Rett syndrome, clinical experience, environmental enrichment animal studies and theories of motor control and motor learning.     

Intervertebral disc disorganization is related to trabecular bone architecture in the lumbar spine.

Cancellous bone morphometry was investigated in the sagittal plane of lumbar vertebrae using histoquantitation. The aim of this study was to identify variations in cancellous bone architecture at increasing states of intervertebral disc (IVD) disorganization after age adjustment and to investigate regional variations within the whole vertebral body. Measurements were taken of the ratio of bone volume (BV) to total volume (TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and trabecular number (Tb.N). Lumbar spines (T12-L5) of 19 men and 8 women were removed at autopsy from an adult sample with no clinical history of bone-related disease or histologically identifiable bone disease. It was found that degeneration of the IVD becomes more common with increasing age. After age-adjustment, significant increases in the proportion of BV/TV were observed in the presence of advancing IVD disorganization. Significant architectural changes were observed in the anterior regions of the vertebral body with increases in Tb.Th and Tb.N and decreases in Tb.Sp. Minimal alterations were found at posterior regions. Bone loss was observed in central regions (most distant from the cortex) as IVD disorganization increased through reduction in both Tb.N and Tb.Th. The BV/TV increase in anterior areas of the centrum may be a response to a redistribution of load to the vertebral body periphery as a result of IVD disorganization. It appears that trabecular morphology is related to the condition of the associated IVD, rather than being the sole consequence of a loss of BV/TV with age. This relationship could influence the occurrence of vertebral body crush fracture.     

Preamble to the proposal for a United Nations second assembly

Maralinga, South Australia was an important site in the United Kingdom nuclear weapons test programme. Seven bombs were exploded and a series of ‘safety’ tests carried out; the latter in particular disseminated appreciable amounts of uranium and plutonium over a wide area. A programme to clean up the test site over several years was instituted, with in-situ vitrification as a principal measure. The final report on the programme has now been published. However, both the programme and the Report are seriously flawed; this article provides criticisms of both.     

Biological and genetic characterization of a low-pathogenicity avian influenza H6N2 virus originating from a healthy Eurasian coot

Influenza A virus, A/Eurasian coot/Western Australia/2727/79 (H6N2), from an apparently healthy coot was characterized. This virus was able to grow on MDCK cells and produce a cytopathic effect in the absence of exogenous trypsin and was further characterized as a low-pathogenicity avian influenza virus, with an intravenous pathogenicity index of 0.15 and a ³²¹PQAETRG³²⁸ motif at the cleavage site of the haemagglutinin gene. It infected domestic chickens, resulting in seroconversion and intermittent virus excretion via cloaca and oropharynx under experimental conditions. Phylogenetic analysis showed that the viral genes were closely related to other waterfowl isolates from the same geographic area and time period.