A repeating fast radio burst source localized to a nearby spiral galaxy.

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

Cell aggregation enhances bone formation by human mesenchymal stromal cells.

The amount of bone generated using current tissue engineering approaches is insufficient for many clinical applications. Previous in vitro studies suggest that culturing cells as 3D aggregates can enhance their osteogenic potential, but the effect on bone formation in vivo is unknown. Here, we use agarose wells to generate uniformly sized mesenchymal stromal cell (MSC) aggregates. When combined with calcium phosphate ceramic particles and a gel prepared from human platelet-rich plasma, we generated a tissue engineered construct which significantly improved in vivo bone forming capacity as compared to the conventional system of using single cells seeded directly on the ceramic surface. Histology demonstrated the reproducibility of this system, which was tested using cells from four different donors. In vitro studies established that MSC aggregation results in an up-regulation of osteogenic transcripts. And finally, the in vivo performance of the constructs was significantly diminished when unaggregated cells were used, indicating that cell aggregation is a potent trigger of in vivo bone formation by MSCs. Cell aggregation could thus be used to improve bone tissue engineering strategies.

The discovery of Arylex™ active and Rinskor™ active: Two novel auxin herbicides.

Multiple classes of commercially important auxin herbicides have been discovered since the 1940s including the aryloxyacetates (2,4-D, MCPA, dichlorprop, mecoprop, triclopyr, and fluroxypyr), the benzoates (dicamba), the quinoline-2-carboxylates (quinclorac and quinmerac), the pyrimidine-4-carboxylates (aminocyclopyrachlor), and the pyridine-2-carboxylates (picloram, clopyralid, and aminopyralid). In the last 10 years, two novel pyridine-2-carboxylate (or picolinate) herbicides were discovered at Dow AgroSciences. This paper will describe the structure activity relationship study that led to the discovery of the 6-aryl-picolinate herbicides Arylex™ active (2005) and Rinskor™ active (2010). While Arylex was developed primarily for use in cereal crops and Rinskor is still in development primarily for use in rice crops, both herbicides will also be utilized in additional crops.

Heterotopic bone formation by nano-apatite containing poly(D,L-lactide) composites.

To render polymeric materials osteoinductive, nano-sized calcium phosphate apatite particles (CaP) were introduced into a low molecular weight poly(D,L-lactide). Homogenous composites were made with 10%, 20% and 40% by weight of apatite content while pure polylactide was used as control. Thereafter porous samples (pore size 300-400 microm, 60% porosity) were fabricated and sterilized. In vitro studies showed that calcium ions were released from the composites depending on the apatite content, while surface mineral deposition was observed only on the 40% CaP composites in simulated body fluid (SBF) within 14 days. After 12 weeks of intramuscular implantation in dogs, only the 40% CaP composite implant retained its shape and showed ectopic bone formation within the pores. In conclusion, adding a content of 40% apatite into poly(D,L-lactide) could lead to an osteoinductive material. Future studies will focus on understanding this phenomenon of material-directed osteoinduction in order to develop a promising bone graft substitute.

Usefulness of point-of-care ultrasound in military medical emergencies performed by young military medicine residents.

INTRODUCTION: To evaluate the usefulness of point-of-care ultrasound (POCUS) performed by young military medicine residents after short training in the diagnosis of medical emergencies. METHODS: A prospective study was performed in the emergency department of a French army teaching hospital. Two young military medicine residents received ultrasound training focused on gall bladder, kidneys and lower limb veins. After clinical examination, they assigned a 'clinical diagnostic probability' (CP) on a visual analogue scale from 0 (definitely not diagnosis) to 10 (definitive diagnosis). The same student performed ultrasound examination and assigned an 'ultrasound diagnostic probability' (UP) in the same way. The absolute difference between CP and UP was calculated. This result corresponded to the Ultrasound Diagnostic Index (UDI), which was positive if UP was closer to the final diagnosis than CP (POCUS improved the diagnostic accuracy), and negative conversely (POCUS decreased the diagnostic accuracy). RESULTS: Forty-eight patients were included and 48 ultrasound examinations were performed. The present pathologies were found in 14 patients (29%). The mean UDI value was +3 (0-5). UDI was positive in 35 exams (73%), zero in 12 exams (25%) and negative in only one exam (2%). CONCLUSION: POCUS performed after clinical examination increases the diagnostic accuracy of young military medicine residents.

Impact of high-dose norepinephrine during intra-hospital damage control resuscitation of traumatic haemorrhagic shock: A propensity-score analysis.

INTRODUCTION: The use of norepinephrine (NE) during uncontrolled haemorrhagic shock (HS) has mostly been investigated in experimental studies. Clinical data including norepinephrine dose and its impact on fluid resuscitation and organ function are scarce. We hypothesized that there is great variability in NE use and that high doses of NE could lead to increased organ dysfunction as measured by the sequential organ failure assessment (SOFA). METHOD: We included patients with HS (systolic blood pressure < 90 mmHg in severely injured patients) who required haemostasis surgery and a transfusion of more than 4 packed red blood cells (PRBC) in the first 6 h of admission and the used of norepinephrine infusion to maintain the blood pressure goal, between admission and the end of haemostasis surgery in a prospective trauma database. A ROC curve determined that, using Youden's criterion, a dose of NE ≥ 0.6 µg/kg/min was the optimal threshold associated with intrahospital mortality. Patients were compared according to this threshold in a propensity score (PS) model. In a generalized linear mixed model, we searched for independent factors associated with a SOFA ≥ 9 at 24 h RESULTS: A total of 89 patients were analysed. Fluid infusion rate ranged from 1.43 to 57.9 mL/kg/h and norepinephrine infusion rate from 0.1 to 2.8 µg/kg/min. The HDNE group received significantly less fluid than the LDNE group. This dose is associated with a higher SOFA score at 24h: 9 (7-10) vs. 7 (6-9) (p = 0.003). Factors independently associated with a SOFA score ≥ 9 at 24 h were maximal norepinephrine rate ≥ 0.6 µg/kg/min (OR 6.69, 95% CI 1.82 - 25.54; p = 0.004), non-blood resuscitation volume < 9 mL/kg/h (OR 3.98, 95% CI 1.14 - 13.95; p = 0.031) and lactate at admission ≥ 5 mmol/L (OR 5.27, 95% CI 1.48 - 18.77; p = 0.010) CONCLUSION: High dose of norepinephrine infusion is associated with deleterious effects as attested by a higher SOFA score at 24 h and likely hypovolemia as measured by reduced non-blood resuscitation volume. We did not find any significant difference in mortality over the long term.

Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2).

The nucleotide sequence of molecular clones of DNA from a retrovirus, ARV-2, associated with the acquired immune deficiency syndrome (AIDS) was determined. Proviral DNA of ARV-2 (9737 base pairs) has long terminal repeat structures (636 base pairs) and long open reading frames encoding gag (506 codons), pol (1003 codons), and env (863 codons) genes. Two additional open reading frames were identified. Significant amino acid homology with several other retroviruses was noted in the predicted product of gag and pol, but ARV-2 was as closely related to murine and avian retroviruses as it was to human T-cell leukemia viruses (HTLV-I and HTLV-II). By means of an SV-40 vector in transfected simian cells, the cloned gag and env genes of ARV-2 were shown to express viral proteins.

Sequence of a cDNA carrying the glycoprotein gene and part of the matrix protein M2 gene of viral haemorrhagic scepticaemia virus, a fish rhabdovirus.

A cDNA clone encoding for the glycoprotein of the viral haemorrhagic scepticaemia virus, a fish rhabdovirus, has been sequenced. The cDNA was 2035 bp long and contained two open reading frames (ORF). A 1523 bp ORF corresponded to the glycoprotein and was adjacent, on its 5' side, to an incomplete 372 bp ORF. Although the protein encoded by this ORF displayed no similarity with other rhabdovirus proteins, it was supposed that the cDNA had been reverse-transcribed from a readthrough mRNA encoding successively for the M2 and the G proteins.

The Ilizarov external fixator: what remains of the wire pretension after dynamic loading?

BACKGROUND: Maintenance of wire pretension in an Ilizarov external fixator is dependent on the torque applied to the fixation bolts. We therefore measured immediately after surgery the clinically applied torques. The median value was only 10 N m (range 8-14N m). We wondered whether this value is appropriate to maintain the wire pretension and thereby to achieve sufficient fracture stability during dynamic loading of the device for a longer period. METHODS: A material testing machine dynamically loaded one wire mounted on one ring. Several configurations were tested. RESULTS: A quick decrease in wire tension to a steady state situation was seen. In the most stable configuration (20 N m wire fixation torque) 50% of the initial 90 kg wire pretension remained after dynamic loading with 200 N. In the least stable configuration (10 N m torque) considerable wire slippage occurred even without loading and no tension remained after loading! No plastic deformation of the wires was observed so loss of wire tension was due to slippage of the wires through the fixation bolts. INTERPRETATION: With the small fixation torques used in clinical practice considerable wire tension is lost even after a few loading cycles. Further research should address the question whether preservation of a higher wire tension during long term loading promotes faster fracture healing.

Expression in Escherichia coli of two mutated genes encoding the cholera toxin B subunit.

To allow subsequent genetically mediated fusion of foreign antigens to cholera toxin B subunit (CTB), two mutated CTB encoding genes (ctxB) were constructed and overexpressed in Escherichia coli. The signal peptide coding sequence was deleted and restriction sites were created at both ends of the modified sequence. Both synthesized CTBs contain additional amino acid(s) at the N terminus (one and three). They were purified as insoluble products and refolded into the natural pentameric CTB structure by a denaturation-renaturation cycle. After renaturation, both recombinant proteins recovered CTB antigenicity and the ability to bind to GM1 gangliosides, as shown by in vitro analysis. Preliminary data indicated that both properties were unaltered by fusion of a foreign peptide to the mutated CTBs.

Stabilization of T7-promoter-based pARHS expression vectors using the parB locus.

We describe a modification of the pAR3040 vector which results in its efficient stabilization during cell division. The parB locus of the plasmid R1 was introduced into the plasmid, pAR3040, to construct the pARHS vectors. These vectors are stable for at least 60 cell generations, even in the absence of selection by an antibiotic present in the culture media, both with or without IPTG induction.

Repair of O6-alkylguanine lesions in DNA by chromatin enzymes.

Disappearance of 7-ethylguanine and O6-ethylguanine lesions from nuclear DNA is observed on incubation of isolated rat liver nuclei previously treated with ethylnitrosourea. Free 7-ethylguanine but no free O6-ethylguanine is released in the medium. Incubation of methylated or ethylated DNA with chromatin proteins leads to the disappearance of O6-methylguanine or O6-ethylguanine from DNA; the methyl group or the ethyl group is transferred to proteins where it is accepted by cystein residues. Repair of O6-methylguanine and repair of O6-ethylguanine lesions in DNA consume a common reactant which is likely the acceptor protein. The repair does not seem however to be a simple bimolecular reaction between the O6-alkylguanine and the cystein of the acceptor protein.

Evidence for two types of non-NMDA receptors in rat cerebellar Purkinje cells maintained in slice cultures.

Pharmacological properties of non-NMDA receptors were investigated in Purkinje cells grown in rat cerebellar slice cultures and recorded in the whole-cell configuration of the patch-clamp technique. Dose-response curves for AMPA and domoate suggest that AMPA, in the concentration range tested, activated only AMPA receptors whereas, domoate activated two types of receptors, probably AMPA and kainate receptors, with EC50 values of 8 and 0.5 microM, respectively. The Scatchard analysis of the dose-response relationship for domoate also suggest that both kainate and AMPA receptors were activated by domoate with approximate affinities of 5 and 0.07 microM-1, respectively. The non-competitive non-NMDA receptors antagonist, GYKI 52466, reduced the amplitude of both AMPA- and domoate-activated currents, with a greater potency in reducing currents evoked by AMPA (IC50 = 10 microM) than those induced by domoate (IC50 = 105 microM). These results suggest that, in addition to AMPA receptors, Purkinje cells express kainate receptors and that these two types of non-NMDA receptors can be distinguished from each other on the basis of several pharmacological properties, including affinity for AMPA, domoate and GYKI 52466.

Modification of the nucleolar structure of the rat oocyte observed just before maturation.

Oocytes removed from antral follicles of 28- to 30-day-old rats treated with FSH (Folligon) show cavities and vesicles in the nucleoli. Repeated injections of Folligon significantly increase the frequency of these nucleolar inclusions. A possible relationship between intranucleolar cavities and rRNA metabolism has been suggested to account for this occurrence.

Identification and production of pestivirus proteins for diagnostic and vaccination purposes.

Using a panel of monoclonal antibodies (MAbs) previously characterized by seroneutralization, immunofluorescence and radioimmunoprecipitation, we have identified Pestivirus proteins useful for diagnostic purposes from the cytopathic Osloss isolate of bovine viral diarrhea virus (BVDV). Proteins that should be useful for vaccination have also been analysed. Cell-free translation of RNA from glycoprotein-coding cDNA fragments produced, when synthesized in the presence of canine pancreatic microsomes, two glycosylated proteins that were independently recognized and immunoprecipitated by two distinct classes of neutralizing MAbs. A similar in vitro procedure was carried out on nonstructural protein-coding sequences and allowed to identify a viral translation product that specifically reacted with MAbs directed against the 80 kDA protein of a number of Pestivirus strains. Its positioning within the polyprotein encoded by the viral genome was refined by epitope scanning using synthetic hexameric peptides. This viral antigen was further expressed in E. coli, produced as inclusion bodies and used successfully as an ELISA antigen in both competitive and indirect assays for the detection of BVD antibodies in cattle sera.

Trachea--innominate artery fistula following tracheostomy. Successful repair using an innominate vein graft.

This report discusses the first recorded patient in whom a trachea--innominate artery fistula after tracheostomy was treated successfully by resection of the eroded segment of artery followed by graft replacement using the patient's left innominate vein. The mechanism of vessel erosion and its prevention are discussed. Also, suitable methods are presented for obtaining temporary control of the severe hemorrhage associated with a tracheoarterial fistula while simultaneously maintaining an adequate airway.

A human immunodeficiency virus Env inducible transcription system to examine consequences of gp120 expression.

According to several studies, the HIV-1 envelope gp120 protein and the co-receptor CXCR4 play an essential role in HIV-1 induced cell toxicity. Characterisation of the CD4-independent m7NDK isolate provided the opportunity of studying the effects of direct interactions between m7NDK gp120 and CXCR4. Therefore, an inducible expression system was designed enabling synthesis of HIV-1 Env proteins upon doxycycline induction. Analysis of the expression of the env gene of the m7NDK HIV-1 isolate revealed, unexpectedly, that even long-term expression of m7NDK gp120 did not result in cytotoxycity in CXCR4-positive or -negative cell lines. This is the first report of a CD4-independent HIV-1-protein inducible expression regulated through the Tet-On system and by an alternative splicing. Env inducible expression cell lines could constitute a useful cellular tool to undertake analysis of HIV Env protein expression.

Malaria and mobility in Thailand.

This paper examines the relationship between malaria transmission and migration in three northern Thai villages. Data and observations indicate that land-poor families forced into swidden farming have greater contact with the primary vectors in Thailand--which breed in small pools in forested areas and shady clearings on hilly scrub terrain. Once infected, migrants from an endemic locus can introduce the parasite into an area with no transmission but potent vectors, thus becoming the cause of explosive epidemics; equally, non-immunes carrying out agricultural activities in or across forest and border areas can themselves be subject to seasonal morbidity. In addition to agricultural activities on clearings near forested areas, clandestine forest activities and cross border traffic contributes to the high prevalence of malaria in Thai border villages. Illegal economic activities--logging, poaching, cattle and goods smuggling--interferes with vector suppression campaigns and prompt detection of infected cases, and ultimately increases human infection not only within the mobile population, but also within the passive population of villages to which the migrants return periodically. Control measures therefore need to take into account the economic pressures which determine a high degree of mobility, the ethnic diversity of the groups which depend on fringe activities for their economic welfare, and the difficult geography of the areas in which they live. As long as economic circumstances forcing human-vector contact receives inadequate attention, better alternatives to current vector control campaigns (which are not effective amongst migrants) are not tried and malaria transmission continues.