Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care.

BACKGROUND: Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. METHODS: Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) assays were used to detect Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, influenza viruses (AH1, AH3 and B), parainfluenza viruses 1-3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. RESULTS: Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p<0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p<0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and Streptococcus pneumoniae (19%) compared with 2% (p<0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. CONCLUSION: Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses

Greasing the protein biosynthesis machinery of photoreceptor neurons: Role for postprenylation processing of proteins

Daily phagocytosis of outer segments (OS) places extraordinary demands on protein biosynthesis and trafficking in photoreceptor neurons. While the members and roles of the phototransduction pathway in the OS are well characterized, details about protein trafficking are just beginning to emerge. Phosphodiesterase6 (PDE6), the effector enzyme in phototransduction cascade, serves as an example of the steps multimeric proteins must pass through to achieve their functional state in the OS. Genetic model systems have recently provided snapshots of various steps in the pathway, as experimental difficulties such as an inability to maintain ciliated photoreceptor outer segments or express functional PDE6 holoenzyme in vitro necessitate in vivo studies. We will highlight the significant findings, their implications to blinding diseases, as well as discuss the gaps requiring further investigation

Myosin-I nomenclature.

We suggest that the vertebrate myosin-I field adopt a common nomenclature system based on the names adopted by the Human Genome Organization (HUGO). At present, the myosin-I nomenclature is very confusing; not only are several systems in use, but several different genes have been given the same name. Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Species Differentiation on a Dynamic Landscape: Shifts in Metapopulation Genetic Structure Using the Chronology of the Hawaiian Archipelago

Species formation during adaptive radiation often occurs in the context of a changing environment. The establishment and arrangement of populations, in space and time, sets up ecological and genetic processes that dictate the rate and pattern of differentiation. Here, we focus on how a dynamic habitat can affect genetic structure, and ultimately, differentiation among populations. We make use of the chronology and geographical history provided by the Hawaiian archipelago to examine the initial stages of population establishment and genetic divergence. We use data from a set of 6 spider lineages that differ in habitat affinities, some preferring low elevation habitats with a longer history of connection, others being more specialized for high elevation and/or wet forest, some with more general habitat affinities. We show that habitat preferences associated with lineages are important in ecological and genetic structuring. Lineages that have more restricted habitat preferences are subject to repeated episodes of isolation and fragmentation as a result of lava flows and vegetation succession. The initial dynamic set up by the landscape translates over time into discrete lineages. Further work is needed to understand how genetic changes interact with a changing set of ecological interactions amongst a shifting mosaic of landscapes to achieve species formation

The SAR11 Group of Alpha-Proteobacteria Is Not Related to the Origin of Mitochondria

Although free living, members of the successful SAR11 group of marine alpha-proteobacteria contain a very small and A+T rich genome, two features that are typical of mitochondria and related obligate intracellular parasites such as the Rickettsiales. Previous phylogenetic analyses have suggested that Candidatus Pelagibacter ubique, the first cultured member of this group, is related to the Rickettsiales+mitochondria clade whereas others disagree with this conclusion. In order to determine the evolutionary position of the SAR11 group and its relationship to the origin of mitochondria, we have performed phylogenetic analyses on the concatenation of 24 proteins from 5 mitochondria and 71 proteobacteria. Our results support that SAR11 group is not the sistergroup of the Rickettsiales+mitochondria clade and confirm that the position of this group in the alpha-proteobacterial tree is strongly affected by tree reconstruction artefacts due to compositional bias. As a consequence, genome reduction and bias toward a high A+T content may have evolved independently in the SAR11 species, which points to a different direction in the quest for the closest relatives to mitochondria and Rickettsiales. In addition, our analyses raise doubts about the monophyly of the newly proposed Pelagibacteraceae family

Mutations in protocadherin 15 and cadherin 23 affect tip links and mechanotransduction in mammalian sensory hair cells

Immunocytochemical studies have shown that protocadherin-15 (PCDH15) and cadherin-23 (CDH23) are associated with tip links, structures thought to gate the mechanotransducer channels of hair cells in the sensory epithelia of the inner ear. The present report describes functional and structural analyses of hair cells from Pcdh15av3J (av3J), Pcdh15av6J (av6J) and Cdh23v2J (v2J) mice. The av3J and v2J mice carry point mutations that are predicted to introduce premature stop codons in the transcripts for Pcdh15 and Cdh23, respectively, and av6J mice have an in-frame deletion predicted to remove most of the 9th cadherin ectodomain from PCDH15. Severe disruption of hair-bundle morphology is observed throughout the early-postnatal cochlea in av3J/av3J and v2J/v2J mice. In contrast, only mild-to-moderate bundle disruption is evident in the av6J/av6J mice. Hair cells from av3J/av3J mice are unaffected by aminoglycosides and fail to load with [3H]-gentamicin or FM1-43, compounds that permeate the hair cell's mechanotransducer channels. In contrast, hair cells from av6J/av6J mice load with both FM1-43 and [3H]-gentamicin, and are aminoglycoside sensitive. Transducer currents can be recorded from hair cells of all three mutants but are reduced in amplitude in all mutants and have abnormal directional sensitivity in the av3J/av3J and v2J/v2J mutants. Scanning electron microscopy of early postnatal cochlear hair cells reveals tip-link like links in av6J/av6J mice, substantially reduced numbers of links in the av3J/av3J mice and virtually none in the v2J/v2J mice. Analysis of mature vestibular hair bundles reveals an absence of tip links in the av3J/av3J and v2J/v2J mice and a reduction in av6J/av6J mice. These results therefore provide genetic evidence consistent with PCDH15 and CDH23 being part of the tip-link complex and necessary for normal mechanotransduction

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Suppression of proline-directed protein kinase FAexpression inhibits the growth of human chronic myeloid leukaemia cells

Initial studies revealed that proline-directed protein kinase FA(PDPK FA) was overexpressed in various cancerous tissues relative to normal controls. However, the functional role of overexpressed PDPK FAin cancer remains to be established. In this report, we explore the potential role of PDPK FAin leukaemia cell growth by investigating the effects of partial inhibition of this kinase on the malignant phenotype of human chronic myeloid leukaemia cells (K562). Cloning of PDPK FAcDNA and its recombinant antisense expression vector and PDPK FA-specific antibody were successfully developed. Two stable antisense clones of K562 cells were subcloned which expressed 70% and 45% of PDPK FArespectively, compared with control-transfected clone in both immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, these two antisense clones expressed no significant suppression of any other related PDPK family members, indicating the specificity of these two antisense clones. Moreover, these antisense clones proportionally and potentially exhibited cell growth retardation, poor clonogenic growth in soft agar and loss of serum independence. The results demonstrate that specific antisense suppression of PDPK FAis sufficient to interfere with the growth of K562 cells, indicating that PDPK FAis essential for human chronic myeloid leukaemia cell growth. © 2000 Cancer Research Campaig

A 6 year Geohelminth infection profile of children at high altitude in Western Nepal

<p>Abstract</p> <p>Background</p> <p>Geohelminth infections are a major problem of children from the developing countries. Children with these infections suffer from developmental impairments and other serious illnesses. This study aimed to measure the prevalence of geohelminth infection, infection intensity as well as the change in the intensity in children from Western Nepal over years.</p> <p>Methods</p> <p>This 6-year hospital based prospective study at the Manipal Teaching Hospital, Pokhara included children (< 15 years) visiting the hospital from Kaski and 7 surrounding districts. Samples were also collected from children in the community from different medical camps. Three stool samples from every child were processed using direct and concentration methods. The Kato-Katz technique was used for measuring the intensity of infection.</p> <p>Results</p> <p>The overall prevalence in hospital - attending children was 9.2% with 7.6% in preschool (0 – 5 y) and 11.0% in school-age (6 – 15 y) children, and in community 17.7% with 14.8% in pre-school and 20.5% in school-age children. <it>Ascaris lumbricoides</it>, <it>Trichuris trichiura</it>, <it>Ancylostoma deodenale </it>and <it>Strongyloides stercoralis </it>were the common geohelminths with a gradual decrease in worm load over the years. School-age children were found to be significantly more prone to geohelminth infection as compared to preschool children, but no statistical difference was detected by gender, district as well as season.</p> <p>Conclusion</p> <p>This heavy infection of geohelminths in children should be corrected by appropriate medication and maintaining strict personal hygiene. Health education, clean water, good sewage management and a congenial environment should be ensured to minimise infection.</p