The quail genome: insights into social behaviour, seasonal biology and infectious disease response.

BACKGROUND: The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. RESULTS: We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organisation, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated after H5N1 infection, and this may be key to the susceptibility of quail to H5N1. CONCLUSIONS: We have produced a high-quality genome of the quail which will facilitate further studies into diverse research questions using the quail as a model avian species.

A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance.

BACKGROUND: Chickens are susceptible to infection with a limited number of Influenza A viruses and are a potential source of a human influenza pandemic. In particular, H5 and H7 haemagglutinin subtypes can evolve from low to highly pathogenic strains in gallinaceous poultry. Ducks on the other hand are a natural reservoir for these viruses and are able to withstand most avian influenza strains. RESULTS: Transcriptomic sequencing of lung and ileum tissue samples from birds infected with high (H5N1) and low (H5N2) pathogenic influenza viruses has allowed us to compare the early host response to these infections in both these species. Chickens (but not ducks) lack the intracellular receptor for viral ssRNA, RIG-I and the gene for an important RIG-I binding protein, RNF135. These differences in gene content partly explain the differences in host responses to low pathogenic and highly pathogenic avian influenza virus in chicken and ducks. We reveal very different patterns of expression of members of the interferon-induced transmembrane protein (IFITM) gene family in ducks and chickens. In ducks, IFITM1, 2 and 3 are strongly up regulated in response to highly pathogenic avian influenza, where little response is seen in chickens. Clustering of gene expression profiles suggests IFITM1 and 2 have an anti-viral response and IFITM3 may restrict avian influenza virus through cell membrane fusion. We also show, through molecular phylogenetic analyses, that avian IFITM1 and IFITM3 genes have been subject to both episodic and pervasive positive selection at specific codons. In particular, avian IFITM1 showed evidence of positive selection in the duck lineage at sites known to restrict influenza virus infection. CONCLUSIONS: Taken together these results support a model where the IFITM123 protein family and RIG-I all play a crucial role in the tolerance of ducks to highly pathogenic and low pathogenic strains of avian influenza viruses when compared to the chicken.

International partnerships and the development of a Sister Hospital Programme.

BACKGROUND: Despite some progress in meeting the Millennium Development Goals, there are still major discrepancies in health service provision between developed and developing countries. Nurses are key players to improving the quality of health services. Increasingly, partnerships are being initiated between nurses of different countries to enable those working in developing countries to improve standards of clinical care. AIM: This paper describes a partnership between two major teaching hospitals: one in Indonesia and one in Australia, designed to assist in improving standards of clinical care within the Indonesian hospital. METHODS: The nature of the partnership, conceptualized as a Sister Hospital Program, is described. The processes and outcomes of the pilot programme conducted in 2011 are outlined. A brief description of the methods used to gain financial support from the Northern Territory Government is provided. The programme offered a skills development programme for selected staff from Sanglah General Hospital in Bali at Royal Darwin Hospital in northern Australia. INSTRUMENTS: The paper uses Green's PROCEED-PRECEDE framework both to describe and evaluate the pilot programme. RESULTS: The skills development programme was enthusiastically evaluated by staff from both hospitals and has led to major changes in the management of patients within the Emergency Department of Sanglah General Hospital. The success of the pilot has resulted in longer-term funding by the Australian government. WIDER POLICY OUTCOMES: The partnership model described in the paper is submitted as a possible framework for others wishing to build long-term and collaborative relationships between nurses of different nations.

Root reinforcement and extracellular products reduce streambank fluvial erosion.

A detailed understanding of the factors that impact bank erodibility is necessary to effectively model changes in channel form. This study evaluated the combined contributions of roots and soil microorganisms to soil resistance against fluvial erosion. To do this, three flume walls were constructed to simulate unvegetated and rooted streambanks. Unamended and organic material (OM) amended soil treatments with either no-roots (bare soil), synthetic (inert) roots, or living roots (Panicum virgatum) were created and tested with the corresponding flume wall treatment. OM stimulated the production of extracellular polymeric substances (EPS) and appeared to increase the applied stress required to initiate soil erosion. Synthetic fibers alone provided a base reduction in soil erosion, regardless of the flow rate used. When used in combination, synthetic roots and OM-amendments reduced erosion rates by 86 % or more compared to bare soil; this reduction was identical to the live rooted treatments (95 % to 100 %). In summary, a synergistic relationship between roots and organic carbon inputs can significantly reduce soil erosion rates due to fiber reinforcement and EPS production. These results indicate that root-biochemical interactions, like root physical mechanisms, play an important role in influencing channel migration rates due to reductions in streambank erodibility.

Inspiral-merger-ringdown waveforms for black-hole binaries with nonprecessing spins.

We present the first analytical inspiral-merger-ringdown gravitational waveforms from binary black holes (BBHs) with nonprecessing spins, that is based on a description of the late-inspiral, merger and ringdown in full general relativity. By matching a post-Newtonian description of the inspiral to a set of numerical-relativity simulations, we obtain a waveform family with a conveniently small number of physical parameters. These waveforms will allow us to detect a larger parameter space of BBH coalescence, including a considerable fraction of precessing binaries in the comparable-mass regime, thus significantly improving the expected detection rates.

Highly pathogenic avian influenza virus H5N2 (clade 2.3.4.4) challenge of mallards age appropriate to the 2015 midwestern poultry outbreak.

BACKGROUND: The 2015 highly pathogenic avian influenza virus (HPAIV) H5N2 clade 2.3.4.4 outbreak in upper midwestern U.S. poultry operations was not detected in wild birds to any great degree during the outbreak, despite wild waterfowl being implicated in the introduction, reassortment, and movement of the virus into North America from Asia. This outbreak led to the demise of over 50 million domestic birds and occurred mainly during the northward spring migration of adult avian populations. OBJECTIVES: There have been no experimental examinations of the pathogenesis, transmission, and population impacts of this virus in adult wild waterfowl with varying exposure histories-the most relevant age class. METHODS: We captured, housed, and challenged adult wild mallards (Anas platyrhynchos) with HPAIV H5N2 clade 2.3.4.4 and measured viral infection, viral excretion, and transmission to other mallards. RESULTS: All inoculated birds became infected and excreted moderate amounts of virus, primarily orally, for up to 14 days. Cohoused, uninoculated birds also all became infected. Serological status had no effect on susceptibility. There were no obvious clinical signs of disease, and all birds survived to the end of the study (14 days). CONCLUSIONS: Based on these results, adult mallards are viable hosts of HPAIV H5N2 regardless of prior exposure history and are capable of transporting the virus over short and long distances. These findings have implications for surveillance efforts. The capture and sampling of wild waterfowl in the spring, when most surveillance programs are not operating, are important to consider in the design of future HPAIV surveillance programs.

A comparative analysis of chromosomal aberrations in cultured human lymphocytes due to fluoroquinolone drugs at different expression periods.

Fluoroquinolones (FQ) are broad-spectrum antibacterial agents widely used for the treatment of infections with various types of gram negative and gram positive bacteria. Specifically, gatifloxacin (GFX) is under development as a component in a new antituberculosis fixed-dose drug combination. In the context of this project, GFX was also tested for genotoxic activity in human peripheral lymphocytes, and the induction of chromosomal aberrations by GFX in PHA-M stimulated cultured human lymphocytes, investigated under conditions of conventional and increased expression times, was further compared to the analogous effects induced by some other second- and third-generation FQ antibacterial agents, namely ofloxacin (OFX), ciprofloxacin (CFX) and sparfloxacin (SFX). OFX did not induce any significant chromosomal aberrations in human lymphocytes. CFX and SFX exhibited slight to moderate clastogenic potential at cytotoxic concentrations (150, 175, 200 and 225 microg/ml), and GFX, a third-generation FQ, induced a clear, concentration-dependent increase in the frequency of chromosomal aberrations at cytotoxic concentrations (150, 200 and 250 microg/ml). These effects were not apparent when metaphases were analysed at the conventionally used sampling time of 24 h, but only after prolongation of the expression time between treatment and harvesting to a sampling time of 36 h (4 h exposure and 32 h expression period). Also, an increased incidence of numerical aberrations (polyploidy and endoreduplication) was seen with GFX at non-cytotoxic concentrations (12.5, 25, 50 and 75 microg/ml). These effects can be attributed to the slight cross-reactivity of FQs between their inhibitory activity towards their intended targets, the prokaryotic type II topoisomerase enzymes DNA gyrase and topoisomerase IV, and the analogous mammalian enzyme topoisomerase II. We have also observed the formation of polycentrics, i.e., chromosomes with five to six centromeres, a rarely reported structural aberration, in GFX-treated cells. The significance of these observations with respect to the conventional conduct of such studies and to the interpretation of the effects is discussed.

Post-fertilization physiology and growth performance of loblolly pine clones.

The physiological processes leading to enhanced growth of loblolly pine (Pinus taeda L.) following fertilization are not clearly understood. Part of the debate revolves around the temporal response of net photosynthetic rate (A(n)) to fertilization and whether the A(n) response is always positive. We measured light-saturated photosynthetic rate (A(sat)), dark respiration rate, growth and crown silhouette area in eight clones of loblolly pine before and after nitrogen (N) fertilization (112 kg ha(-1)) to track the initial physiological changes prior to any changes in growth. Overall, there were positive photosynthetic and growth responses to fertilization; however, there were pronounced physiological and growth differences among clones, even among clones with the same parents. Clones 4, 6 and 7 showed large volume growth and A(sat) responses to fertilization. Clone 1 and Clone 8 (a full-sibling of Clone 7) mainly showed a volume growth response, whereas Clone 2 (full-sibling of Clone 1) showed an A(sat) response only. Clone 5 (full-sibling of Clone 6) showed little response to fertilization, whereas Clone 3 (full-sibling of Clone 4) showed a negative A(sat) response. Thus, within-family variation warrants further study to ensure that relatively expensive clonal material is used efficiently.

Activation of STAT5 during EPO-directed suppression of apoptosis.

The ligand-dependent activation of the JAK/STAT (Januskinase/Signal Transducer and Activator of Transcription) pathway has been implicated in the explanation of cytokine-specific regulation of gene expression. Previous studies have reported conflicting results on the role of the transcription factor STAT5 in erythropoietin (EPO)-induced cellular responses. In this study we focused on the functional importance of STAT5 docking sites in the intracellular EPO receptor (EPOR) domain for the mediation of antiapoptotic activities. We demonstrate that EPO-dependent survival of erythroleukemic cell lines is accompanied by sustained STAT5 DNA-binding activity. The role of single tyrosine residues was dissected by the analysis of myeloid FDCP-1 cells stably expressing mutant EPOR proteins. The data show that receptors having a high potential to mediate antiapoptotic signals also effectively activate STAT5, whereas receptors lacking STAT5 docking sites are diminished in both activities. We conclude that the transcription factor STAT5 is functionally implicated in the EPO-dependent survival of cells.

Induction of erythroid proliferation and differentiation by a trophoblast-specific cytokine involves activation of the JAK/STAT pathway.

Pregnancy is characterized by increased erythropoiesis within maternal and fetal compartments. The placenta has been shown to produce factors that stimulate erythropoiesis but convincing evidence for placental production of erythropoietin (EPO) is still lacking. Prolactin-like protein E (PLP-E) was recently found to stimulate expression of the adult beta major globin gene in mouse erythroleukemia cells. Here we demonstrate that PLP-E transiently expressed in COS-7 cells stimulates proliferation and erythroid differentiation of murine and human erythroid progenitor cell lines. Electrophoretic mobility shift assays were used to show the activation of STAT5 by PLP-E in the human erythroid cell line TF1. Furthermore, we compared the effects of PLP-E on murine myeloid FDCP1 cells which do not express EPO receptors (EPORs) with effects on cells genetically engineered to express functional EPORs. We provide evidence that PLP-E-dependent proliferation and STAT5 activation is independent of the expression of the EPOR. Taken together, these data suggest that PLP-E acts on specific receptors of erythroid-committed murine and human cells by the activation of intracellular signaling pathways promoting cell growth and differentiation.

Laparoscopic placement of ventriculoperitoneal shunts: preliminary report.

We used a laparoscopic technique for the percutaneous placement of the peritoneal end of cerebrospinal fluid shunts in adult patients with obstructive or normal-pressure hydrocephalus. Concurrent with the initial cranial part of the procedure, pneumoperitoneum is established in a routine fashion, and a video-laparoscope and grasping forceps are inserted into the peritoneal cavity. With use of a pacemaker introducer kit, the peritoneal catheter is placed percutaneously under direct laparoscopic vision through a small upper abdominal incision into the peritoneal cavity. At the completion of the procedure, the patency of the assembled shunt system can be verified by observing free flow of cerebrospinal fluid from the catheter tip as the valve is being pumped. We found that this technique is particularly useful in technically challenging cases--for example, those involving obese patients and those who have undergone multiple abdominal operations. No complications associated with the technique were encountered.

The demise of vaginal operative obstetrics: a suggested plan for its revival.

Predictions made more than a quarter of a century ago regarding excessive use of cesarean delivery for cases of dystocia have been realized. Breech presentation, correctable dystocia, and twin gestation are increasingly being delivered by the abdominal route. Recent studies have shown that neonatal morbidity is not inherently improved by cesarean birth, and in fact have reported comparable results with vaginal operative procedures in properly selected and managed cases. Pressure to control the cesarean birth rate is now being exerted by consumer groups, professional groups, and governmental agencies. The reintroduction of vaginal operative procedures to modern obstetrics would help reduce the cesarean birth rate. However, major changes in the medical liability system, medical education and training, and the method of certifying obstetricians will be required before vaginal operative obstetrics becomes a serious alternative to cesarean delivery. Without these changes, I believe there is little hope of reversing the trend toward cesarean birth.

Routine electronic monitoring of fetal heart rate and uterine activity during labor.

Routine electronic monitoring has been performed on 2411 labor patients at Booth Memorial Medical Center. Most recently, 88% of all patients delivered were monitored. As a direct result of this program, intrapartum stillbirths have been dramatically reduced from 1.2/1000 livebirths to 0.5/1000 livebirths. Perinatal mortality for fetuses over 1000 g has fallen to 8.8/1000 deliveries. Apgar scores below 6 at 5 minutes have decreased from a rate of 24/1000 to 14/1000 livebirths. No increase in cesarean sections for fetal distress has occurred although the primary cesarean section rate has increased over the past 10 years, apparently unrelated to fetal monitoring. It is strongly recommended that all patients in labor be monitored by currently available technics.

Tubal sterilization by bipolar laparoscopy: report of 232 cases.

Two hundred thirty-two interval bipolar laparoscopic tubal sterilizations were performed in a university-affiliated community teaching hospital over a 3-year period. Advanced laparoscopy equipment, properly trained laparoscopists, and a system of delineated operating privileges were used; the complication rate was 0.8%. There was 1 intraoperative complication, and 1 postoperative complication that manifested itself on postoperative day 3. Neither complication was related to the electrocauterization. The cauterized segments of fallopian tube were intentionally transected in 195 (84%) of the patients. The equipment and methodology employed are discussed with comparison of bipolar electrocautery to mechanical nonelectric methods of laparoscopic sterilization, ie, bands and clips. The authors' preference for bipolar electrocautery tubal sterilization, using single-segment cauterization with tubal transection, is discussed.

PIP: 232 interval bipolar laparoscopic tubal sterilizations were performed in a university-affiliated community teaching hospital over a 3-year period. Advanced laparoscopy equipment, properly trained laparoscopists, and a system of delineated operating privileges were used; the complication rate was .8%. There was 1 intraoperative complication and 1 postoperative complication that manifested itself on postoperative day 3. Neither complication was related to the electrocauterization. The cauterized segments of fallopian tube were intentionally transected in 195 (84%) of the patients. The equipment and methodology employed are discussed with comparison of bipolar electrocautery to mechanical nonelectric methods of laparoscopic sterilization, i.e., bands and clips. The authors' preference for bipolar electrocautery tubal sterilization, using single-segment cauterization with tubal transection, is discussed.

Laparoscopic cauterization of endometriosis for fertility: a controlled study.

Ninety infertility patients with moderate endometriosis were randomized between laparoscopic electrocautery and 6 months of danazol therapy and studied for 7 months after treatment. Twenty of the 45 patients undergoing electrocautery conceived (44%) during the follow-up interval. Forty-one of the 45 patients in the danazol group completed the course of therapy, and 16 of those conceived (39%) during the same follow-up interval. There was no statistical difference between the two groups (P less than 0.53). No patients in the electrocautery group experienced complications. This demonstrates that electrocautery is safe and effective in the treatment of moderate endometriosis.

Autogenous intrasynovial and extrasynovial tendon grafts: an experimental study of pro alpha 1(I) collagen mRNA expression in dogs.

On the basis of recent evidence that the healing processes of tendon grafts are donor-tissue specific, in situ hybridization, using a 372 bp cDNA fragment complementary to a portion of pro alpha 1(I) collagen mRNA, was utilized to compare the cellular responses to transplantation exhibited by autogenous intrasynovial and extrasynovial flexor tendon grafts. Intrasynovial and extrasynovial tendons from the hindpaw were transferred to synovial sheaths in the forepaw of 12 mongrel dogs (24 tendons) and treated with immediate controlled passive motion. The tendon grafts were harvested at 2, 4, and 6 weeks, and each was divided into a proximal, central (8 mm), and distal portion. Sections from the central portion were embedded in paraffin and subjected to in situ hybridization, autoradiography, and staining; levels of procollagen mRNA then were assessed by microscopic examination. The two types of tendon grafts exhibited different levels of pro alpha 1(I) collagen mRNA expression at all three time points. Intrasynovial tendon grafts displayed no areas of increased type-I procollagen mRNA at 2, 4, and 6 weeks. The extrasynovial tendon grafts displayed increased surface levels of type-I procollagen mRNA at 2 and 4 weeks; the levels decreased to background levels by 6 weeks. The high levels of procollagen mRNA exhibited by the extrasynovial grafts suggest increased collagen synthetic activity, indicative of a cellular response to injury, whereas the preservation of low levels of expression in the intrasynovial grafts may signify a less inflammatory cellular response.

In vitro biomechanical analysis of suture methods for flexor tendon repair.

This study was designed to compare five different suture methods that are used clinically for tendon repair. The flexor digitorum profundus tendons from the digits of adult mongrel dogs and adult human cadavers were used as models. The tendons in zone II of the hand, defined as the region from the distal palmar crease to the insertion of the flexor digitorum superficialis tendon at the middle phalanx, were transected and then were repaired by one of the suture methods developed by Kessler, Tsuge, Tajima, Savage, or Lee. The gliding function and tensile properties of the repaired tendons were evaluated biomechanically at time zero. The Tajima and Savage methods produced better gliding function than the other techniques. In the canine specimens that had been repaired by one of these two methods, the rotation of the distal interphalangeal joint was more than 60% of the rotation of the canine control specimens; only the Savage technique produced a rotation 124% that of the human control specimens. After the Tajima repair, the rotation of the proximal interphalangeal joint was 113% that of the canine control specimens and 157% that of the human controls. In the canine specimens that had had the Tajima or Savage repair, excursion of the tendon was greater than 55% that of the controls. The tendons repaired by the Savage method tolerated a significantly higher ultimate load to failure (14 and 25% that of the canine and human control specimens, respectively) than the other methods.(ABSTRACT TRUNCATED AT 250 WORDS)

The toxicology of iodate: a review of the literature.

Because it is more stable than iodide, most health authorities preferentially recommend iodate as an additive to salt for correcting iodine deficiency. Even though this results in a low exposure of at most 1,700 microg/d, doubts have recently been raised whether the safety of iodate has been adequately documented. In humans and rats, oral bioavailability of iodine from iodate is virtually equivalent to that from iodide. When given intravenously to rats, or when added to whole blood or tissue homogenates in vitro or to foodstuff, iodate is quantitatively reduced to iodide by nonenzymatic reactions, and thus becomes available to the body as iodide. Therefore, except perhaps for the gastrointestinal mucosa, exposure of tissues to iodate might be minimal. At much higher doses given intravenously (i.e., above 10 mg/kg), iodate is highly toxic to the retina. Ocular toxicity in humans has occurred only after exposure to doses of 600 to 1,200 mg per individual. Oral exposures of several animal species to high doses, exceeding the human intake from fortified salt by orders of magnitude, pointed to corrosive effects in the gastrointestinal tract, hemolysis, nephrotoxicity, and hepatic injury. The studies do not meet current standards of toxicity testing, mostly because they lacked toxicokinetic data and did not separate iodate-specific effects from the effects of an overdose of any form of iodine. With regard to tissue injury, however, the data indicate a negligible risk of the small oral long-term doses achieved with iodate-fortified salt. Genotoxicity and carcinogenicity data for iodate are scarce or nonexisting. The proven genotoxic and carcinogenic effects of bromate raise the possibility of analogous activities of iodate. However, iodate has a lower oxidative potential than bromate, and it did not induce the formation of oxidized bases in DNA under conditions in which bromate did, and it may therefore present a lower genotoxic and carcinogenic hazard. This assumption needs experimental confirmation by proper genotoxicity and carcinogenicity data. These in turn will have to be related to toxicokinetic studies, which take into account the potential reduction of iodate to iodide in food, in the intestinal lumen or mucosa, or eventually during the liver passage.

Amputation after extremity injury.

Extremity injury is a significant cause of morbidity and mortality in the trauma patient. The decision to amputate is a difficult one to make in a patient population still in the productive years of life. At the University of Louisville Hospital from 1976 to 1984, 37 patients with traumatic extremity injury required amputation. Ninety percent of these injuries were to the lower extremities. A decision for amputation was based on the absence of neurovascular function, the presence of fracture of the involved extremity, the presence of a large soft tissue defect, and the presence of severe contamination. Prompt amputation of such severely damaged limbs may be preferable to attempts at salvage. Early amputation offers the opportunity for prosthetic replacement and good long-term functional recovery.

Uptake, metabolism and mutagenic activity of aromatic glycidyl compounds.

Aromatic diglycidyl compounds are very active mutagens when assayed in in vitro tests. In vivo, however, resorcinol diglycidyl ether provided no evidence for the clastogenic activity, while diglycidylaniline exhibited definite mutagenic activity in the micronucleus test. Since the only difference between these two compounds lies in the binding mode of the glycidyl groups to the aromatic nucleus (i.e. ether oxygen vs. aminic nitrogen), this apparent discrepancy in mutagenic activity led to the question of the mechanisms involved in such an activity difference. Although no clear signs of differential uptake or excretion could be detected in mice, differences could be seen in the spectrum of urinary metabolites; while resorcinol diglycidyl ether seemed to become fully converted to the genetically inactive bis-diol compound, a sizeable proportion of diglycidylaniline was converted only to the diol-epoxide. In vitro investigations and enzyme kinetic measurements with postmitochondrial supernatant of rat or mouse liver homogenate (S-9) finally yielded the biochemical explanation for this behaviour, as they showed a very low affinity of the diol-epoxide metabolite of diglycidylaniline for the epoxide hydrolase, normally involved in the degradation of such compounds. The diol-epoxide obtained from resorcinol diglycidyl ether, on the other hand, has an affinity to the degradation enzyme similar to, or even higher than, the one measured with the parent substance.