Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor.

Spermatozoa undergo a poorly understood activation process induced by bicarbonate and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed that bicarbonate mediates its effects through changes in intracellular pH or membrane potential; however, we demonstrate here that bicarbonate directly stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro in a pH-independent manner. sAC is most similar to adenylyl cyclases from cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in these early forms of life. sAC is also expressed in other bicarbonate-responsive tissues, which suggests that bicarbonate regulation of cAMP signaling plays a fundamental role in many biological systems.

Top research priorities in healthcare-associated infection in the UK.

BACKGROUND: There is a mismatch between research questions which are considered to be important by patients, carers and healthcare professionals and the research performed in many fields of medicine. No relevant studies which have assessed research priorities in healthcare-associated infection (HCAI) that have involved patients' and carers' opinions were identified in the literature. AIM: The Healthcare-Associated Infections Priority Setting Partnership was established to identify the top research priorities in the prevention, diagnosis and treatment of HCAI in the UK, considering the opinions of all these groups. METHODS: The methods broadly followed the principles of the James Lind Alliance (JLA) priority setting activity. FINDINGS: In total, 259 unique valid research questions were identified from 221 valid responses to a consultation of patients, carers and healthcare professionals after seeking their opinions for research priorities. The steering committee of the priority setting partnership rationalized these to 50 unique questions. A literature review established that for these questions there were no recent high-quality systematic reviews, high-quality systematic reviews which concluded that further studies were necessary, or the steering committee considered that further research was required despite the conclusions of recent systematic reviews. An interim survey ranked the 50 questions, and the 10 main research priorities were identified from the top 32 questions by consensus at a final priority setting workshop of patients, carers and healthcare professionals using group discussions. CONCLUSIONS: A priority setting process using JLA methods and principles involving patients, carers and healthcare professionals was used to identify the top 10 priority areas for research related to HCAI. Basic, translational, clinical and public health research would be required to address these uncertainties.

Cloning and characterization of a Drosophila adenylyl cyclase homologous to mammalian type IX.

A novel Drosophila adenylyl cyclase (AC) was identified by PCR using degenerate primers specific for the known metazoan ACs. The full-length cDNA predicts a protein displaying significant sequence homology with mammalian Type IX AC (AC9). The abundance and size of the message for the Drosophila AC9 homolog (DAC9) changes through development. Biochemical analysis of DAC9 confirms it encodes a functional enzyme which can be activated by forskolin or G protein. Together with the Drosophila Type I AC homolog encoded by the learning and memory gene, rutabaga, the molecular identification of DAC9 demonstrates there is a family of Drosophila AC isoforms reflecting at least part of the diversity of mammalian AC isoforms.

Multichannel, direct-reading spectrograph attachment.

An instrument is described which provides a multichannel direct-reading capability for photoelectric spectrographic detection. The important feature of the instrument is the ability of the user to select at will any combination of channels for position adjustment and to move these while preserving the optical integrity of the enclosure. Photomultipliers are used and the results of performance tests are described.

[The management of post donation information: a fundamental element of blood safety]. / La gestion des informations post-don: un élément fondamental de la sécurité transfusionnelle.

Post donation information management is a fundamental axis of haemovigilance in terms of blood safety. It requires an organization ensuring a permanent reactivity, a good sensitization of French National Blood Service professionals and needs also a strong awareness of blood donors. Previous identification of stakeholders to warn during these kinds of alerts is essential to avoid the use of any blood product presenting a potential risk. The recent implementation of a consensual internal document aims to target the reinforcement of a homogeneous decision-making process, combining blood product self-sufficiency and above all recipient safety.

Sodium regulation of GAF domain function.

Cyclic nucleotide PDEs (phosphodiesterases) regulate cellular levels of cAMP and cGMP by controlling the rate of degradation. Several mammalian PDE isoforms possess N-terminal GAF (found in cGMP PDEs, Anabaena adenylate cyclases and Escherichia coli FhlA; where FhlA is formate hydrogen lyase transcriptional activator) domains that bind cyclic nucleotides. Similarly, the CyaB1 and CyaB2 ACs (adenylate cyclases) of the cyanobacterium Anabaena PCC 7120 bind cAMP through one (CyaB1) or two (CyaB2) N-terminal GAF domains and mediate autoregulation of the AC domain. Sodium inhibits the activity of CyaB1, CyaB2 and mammalian PDE2A in vitro through modulation of GAF domain function. Furthermore, genetic ablation of cyaB1 and cyaB2 gives rise to Anabaena strains defective in homoeostasis at limiting sodium. Sodium regulation of GAF domain function has therefore been conserved since the eukaryotic/prokaryotic divergence. The GAF domain is the first identified protein domain to directly sense and signal changes in environmental sodium.

Light Sources in the 0.15-20-micro Spectral Range.

The different kinds of light sources available for the 0.15-20-micro spectral range are surveyed. Information was obtained from the published literature, unpublished reports, light source manufacturers, and also from individual persons. The aim has been to present sufficient information, where available, to show the relative advantages of different sources-intensity, stability, and output uniformity were of prime interest. Continuum and line sources are included but lasers and pulsed sources are omitted. The sources are described under the main headings: Arc Discharge Sources, Glow Discharge Sources, and Incandescent Sources, with another section, Miscellaneous Sources, to cover some which could not be included under the first three headings.

Restricted expression of a truncated adenylyl cyclase in the cephalic furrow of Drosophila melanogaster.

We have identified a novel isoform of adenylyl cyclase, DAC78C, in Drosophila melanogaster that encodes two structurally distinct proteins in a developmentally restricted manner. The protein corresponding to one transcript is potently activated by G protein and protein kinase C and is expressed ubiquitously. The protein corresponding to the second transcript is expressed in a dynamic pattern in gastrulation stage embryos; it is restricted to the cephalic furrow and dorsal transverse folds, active regions of cell movement of unknown function in the Drosophila embryo. We propose that DAC78C and the cAMP pathway play an important role in directing these morphogenetic movements, and that this gene may provide clues to the functional significance of these structures in gastrulation.

A new family of adenylyl cyclase genes in the male germline of Drosophila melanogaster.

We describe the cloning and characterization of a new gene family of adenylyl cyclase related genes in Drosophila. The five adenylyl cyclase-like genes that define this family are clearly distinct from previously known adenylyl cyclases. One member forms a unique locus on chromosome 3 whereas the other four members form a tightly clustered, tandemly repeated array on chromosome 2. The genes on chromosome 2 are transcribed in the male germline in a doublesex dependent manner and are expressed in postmitotic, meiotic, and early differentiating sperm. These genes therefore provide the first evidence for a role for the cAMP signaling pathway in Drosophila spermatogenesis. Expression from this locus is under the control of the always early, cannonball, meiosis arrest, and spermatocyte arrest genes that are required for the G2/M transition of meiosis I during spermatogenesis, implying a mechanism for the coordination of differentiation and proliferation. Evidence is also provided for positive selection at the locus on chromosome 2 which suggests this gene family is actively evolving and may play a novel role in spermatogenesis.

Atmospheric transmittance in the region near the 4.3-microm band head of CO(2).

Simulations have been made of atmospheric-transmittance spectra over a 5.1-km sea-level path measured by the Naval Research Laboratory, Washington, D.C. New CO(2) line-profile form factors were used that had been obtained previously from experiment. The simulations were found to agree well with the field spectra, supporting the validity of the CO(2) line profiles used.

Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals.

Mammals have nine differentially regulated isoforms of G protein-responsive transmembrane-spanning adenylyl cyclases. We now describe the existence of a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or Forskolin regulation. Northern analysis indicates the gene encoding soluble adenylyl cyclase (sAC) is preferentially expressed in testis. As purified from rat testis cytosol, the active form of sAC appears to be a fragment derived from the full-length protein, suggesting a proteolytic mechanism for sAC activation. The two presumptive catalytic domains of sAC are closely related to cyanobacterial adenylyl cyclases, providing an evolutionary link between bacterial and mammalian signaling molecules.

Carbon dioxide spectral line frequencies for the 4.3-microm region.

The frequencies of CO(2) lines in the 3.77-4.26-microm region, which were obtained experimentally, have been compared with those listed on two tapes of the AFCRL Atmospheric Absorption Line Parameters Compilation. The experimental line frequencies were obtained in absorption using a high-resolution Michelson interferometer. Discrepancies between the present experimental values and the frequencies listed on the AFCRL tapes are tabulated. Consistency checks were also made by comparing calculated line frequencies with those on the tapes, and these findings are also reported.

High resolution atmospheric transmission calculations down to 28.7 km in the 200-243-nm spectral range.

Decrease in stratospheric ozone absorption and increase in oxygen absorption with decreasing wavelength combine to produce a window of maximum atmospheric transmission near 210 nm. Since solar radiation in this spectral region dissociates molecular oxygen, the deep atmospheric penetration at this wavelength is of particular aeronomical interest. High resolution calculations of the transmittance down to 28.65 km were made for the 200-243-nm spectral range in this window region, in support of a stratospheric balloon flight from Fort Churchill in July 1974. The calculations were made by dividing the atmosphere into layers which were chosen so that each could be assumed homogeneous; optical depths were calculated separatelyfor each of these layers and then summed to obtain the over-all transmittance of the atmosphere. Absorptionby molecular oxygen (line and continuum) and by ozone was included, as well as extinction through Rayleigh scattering by air molecules. The calculated transmittances were combined with hig h altitude(above 100-km) rocket measurements of the sun-center spectrum and center-to-limb variations to give residual high resolution solar spectral flux for several altitudes and solar zenith angles.