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Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. CEMIP is overexpressed in a variety of pathological conditions, and the inhibition of its hyaluronidase activity therefore has therapeutic potential. To identify novel inhibitors of the CEMIP hyaluronidase activity, we established here a cell-compatible, medium-throughput assay for CEMIP-dependent HA depolymerization. The assay employs ultrafiltration plates to separate low- from high-molecular-weight HA, followed by quantification of HA fragments using an HA ELISA-like assay. Using this assay, we tested a range of compounds that have been reported to inhibit other hyaluronidases. Thereby, we identified several sulfated hydrocarbon polymers that inhibit CEMIP more potently than other hyaluronidases. One of these is heparin, a sulfated glycosaminoglycan produced by mast cells that constitutes the first described physiological CEMIP inhibitor. The most potent inhibitor (IC50 of 1.8 nM) is dextran sulfate, a synthetic sulfated polysaccharide. Heparin and dextran sulfate are used in numerous established and experimental biomedical applications. Their ability to inhibit CEMIP needs to be taken into account in these contexts.

Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. CEMIP is overexpressed in a variety of pathological conditions, and the inhibition of its hyaluronidase activity therefore has therapeutic potential. To identify novel inhibitors of the CEMIP hyaluronidase activity, we established here a cell-compatible, medium-throughput assay for CEMIP-dependent HA depolymerization. The assay employs ultrafiltration plates to separate low- from high-molecular-weight HA, followed by quantification of HA fragments using an HA ELISA-like assay. Using this assay, we tested a range of compounds that have been reported to inhibit other hyaluronidases. Thereby, we identified several sulfated hydrocarbon polymers that inhibit CEMIP more potently than other hyaluronidases. One of these is heparin, a sulfated glycosaminoglycan produced by mast cells that constitutes the first described physiological CEMIP inhibitor. The most potent inhibitor (IC50 of 1.8 nM) is dextran sulfate, a synthetic sulfated polysaccharide. Heparin and dextran sulfate are used in numerous established and experimental biomedical applications. Their ability to inhibit CEMIP needs to be taken into account in these contexts. [ABSTRACT FROM AUTHOR]

A metagenomic analysis of the virome of honey bees (Apis mellifera) from an apiary with high rates of unexplained colony losses identified a novel RNA virus. The virus, which was named Apis mellifera solinvivirus 1 (AmSV1), contains a 10.6 kb positive-strand genomic RNA with a single ORF coding for a polyprotein with the protease, helicase, and RNA-dependent RNA polymerase domains, as well as a single jelly-roll structural protein domain, showing highest similarity with viruses in the family Solinviviridae. The injection of honey bee pupae with AmSV1 preparation showed an increase in virus titer and the accumulation of the negative-strand of AmSV1 RNA 3 days after injection, indicating the replication of AmSV1. In the infected worker bees, AmSV1 was present in heads, thoraxes, and abdomens, indicating that this virus causes systemic infection. An analysis of the geographic and historic distribution of AmSV1, using over 900 apiary samples collected across the United States, showed AmSV1 presence since at least 2010. In the year 2021, AmSV1 was detected in 10.45% of apiaries (95%CI: 8.41–12.79%), mostly sampled in June and July in Northwestern and Northeastern United States. The diagnostic methods and information on the AmSV1 distribution will be used to investigate the connection of AmSV1 to honey bee colony losses.

This review was commissioned by the Victorian Attorney-General,The Hon Rob Hulls MP, following the recent case of McCabe in the Supreme Court of Victoria. Mrs McCabe suffered from lung cancer which she attributed to the smoking over many years of cigarettes produced by British American Tobacco Australia Services Limited (BAT). She sued BAT for personal injuries caused by its alleged negligence, and claimed damages.At the trial, the trial judge struck out BAT’s defence, thus awarding the case to Mrs McCabe. He did so on the basis that BAT had failed to comply with a series of discovery orders he had earlier made, requiring the company to produce various documents relevant to Mrs McCabe’s case.BAT was unable to produce many of these documents because over a period of years they had been destroyed pursuant to a number of document retention policies devised by the Company. BAT appealed to the Court of Appeal against the decision of the trial judge to strike out its defence. The Court allowed the appeal and in doing so made new law for Victoria on the key issue of principle which had arisen, of what the position should be when documents relevant to litigation have been destroyed in advance of the formal commencement of legal proceedings. On this question the Court of Appeal said that the document destruction in McCabe was not unlawful because it took place before the commencement of litigation.The Court also said that decisions of the type made by the trial judge in McCabe to strike out a defence would only be justified in future cases if the precommencement destruction amounted to an attempt to pervert the course of justice or, if open, contempt of court.The broad policy conclusion reached by this review is that the exercise of a trial judge’s discretion in civil litigation to rule on the consequences of failure by parties to comply with discovery rules should not be limited to circumstances in which formal legal proceedings have been commenced. It should extend to certain pre-commencement situations.The main reasons for this general conclusion are to ensure fairness in civil litigation; to enable the courts to decide cases on the basis of as much relevant evidence and information as possible; and to preserve and enhance the overall integrity and reputation of the civil justice process and therefore the justice system as a whole. Destruction of relevant documents is a serious matter and can adversely affect individual parties to litigation as well as damage community confidence in the system of justice itself. This can be so whether the destruction occurs after or before the commencement of litigation.To deal with this important issue, a three-pronged approach is proposed in this report. First, there should be a new statutory provision applicable to civil proceedings in all the Victorian courts, giving judicial officers very similar discretionary powers in dealing with pre-commencement document destruction as those available if destruction occurs after proceedings have been formally commenced. The second proposal is that Victoria should have a new statutory criminal offence dealing with the destruction of documentary material which is relevant to a judicial proceeding. This statute would deal with the worst and most blatant instances of the destruction of material relevant to civil litigation and would cover highly negligent destructions as well as intentional ones. It should cover cases of pre-commencement destruction as well as those post-commencement of proceedings.The third key proposal is that there should be a new professional conduct regulation, as there now is in New South Wales, to apply where advice is given by lawyers to clients about document retention and destruction and also to situations where lawyers themselves are in possession or control of material which is relevant to actual or reasonably anticipated litigation. This regulation would be aimed at guiding the day-to-day operations of legal practitioners in this area, both solicitors and barristers, as distinct from dealing with a particular case before a court or an actual allegation of destruction so serious that it could give rise to possible criminal liability.The particular Recommendations are set out in the next section of the report.They are expressed in reasonably broad, general terms. This is because the main thrust of this review has been to identify the key public and legal policy issues which arise in this area and to suggest what the appropriate responses might be.The drafting of any specific statutory and regulatory provisions should be left to the relevant experts, depending upon decisions that the Attorney-General and the Government as a whole may make in relation to the Recommendations.

Au 16e siècle, les entradas espagnoles dans le continent nord-américain – en Floride, dans la vallée du Mississippi, au Nouveau-Mexiqu – ont donné lieu à plusieurs chroniques qui nous informent sur les moyens mis en œuvre, le déroulement des expéditions, les buts visés par leurs participants, ainsi que les rapports que ces derniers ont entretenus avec les populations indigènes. Cet article permet de juger des qualités et des limites de ces documents.

A metagenomic analysis of the virome of honey bees (Apis mellifera) from an apiary with high rates of unexplained colony losses identified a novel RNA virus. The virus, which was named Apis mellifera solinvivirus 1 (AmSV1), contains a 10.6 kb positive-strand genomic RNA with a single ORF coding for a polyprotein with the protease, helicase, and RNA-dependent RNA polymerase domains, as well as a single jelly-roll structural protein domain, showing highest similarity with viruses in the family Solinviviridae. The injection of honey bee pupae with AmSV1 preparation showed an increase in virus titer and the accumulation of the negative-strand of AmSV1 RNA 3 days after injection, indicating the replication of AmSV1. In the infected worker bees, AmSV1 was present in heads, thoraxes, and abdomens, indicating that this virus causes systemic infection. An analysis of the geographic and historic distribution of AmSV1, using over 900 apiary samples collected across the United States, showed AmSV1 presence since at least 2010. In the year 2021, AmSV1 was detected in 10.45% of apiaries (95%CI: 8.41–12.79%), mostly sampled in June and July in Northwestern and Northeastern United States. The diagnostic methods and information on the AmSV1 distribution will be used to investigate the connection of AmSV1 to honey bee colony losses. [ABSTRACT FROM AUTHOR]

The velocity at which blood lactate concentration ([LA]) of 4 mmol/L is reached ([v.sub.4]) is widely used to determine fitness, but there are few published data on using [LA] as a guide for the exercise speed for training in horses. In this study, the effect of 3 conditioning programs with [LA] guided exercise speeds on [V.sub.4], [V.sub.200] (speed at a heart rate of 200 beats/min), blood [LA], plasma FFA ([FFA]), and alanine concentrations ([alanine]), before and after exercise, as well as heart rate during exercise, of horses was examined. Six 2-yr-old Haflinger stallions underwent an initial treadmill-based standard exercise test (SET). A regression analysis [LA]-speed relationship was used to calculate [v.sub.1.5], [v.sub.2.5], and [v.sub.4]. Horses were then randomly assigned to 1 of 3 conditioning programs according to a 3 x 6 Latin square design. During 6 wk, horses exercised on the treadmill every other day for 45 min at their calculated [v.sub.1.5] or [v.sub.2.5] or 25 min at their [v.sub.4]. Each conditioning period (CDP) was followed by 5 wk without conditioning. At 2 and 9 d, and 5 wk, after the end of the CDP, the horses performed another SET to evaluate again the [v.sub.4] and [v.sub.200]. Blood [LA], plasma [FFA], and [ala nine] were measured before and after heart rate during exercise sessions 1, 11, and 21 in each CDP. None of the exercise programs had an effect on [v.sub.4] and [v.sub.200] (P > 0.05). The increase of the mean [LA] after exercise decreased during CDP (P < 0.05), and the increase of mean heart rate during exercise tended to decrease as well (P = 0.07). There was no difference among the conditioning programs. Plasma [FFA] before exercise was not influenced by the CDP (P > 0.05). The plasma [FFA] was always greater after exercise (P < 0.05), but there was no difference among conditioning programs. Overall, the increase was greatest after the 21st exercise session compared with the 1st and 11th exercise sessions (P < 0.05). The mean plasma [alanine] before exercise remained similar during all CDP (P > 0.05). Mean plasma [alanine] of the horses was increased after all exercise sessions measured (P < 0.05). There was no difference among conditioning programs (P > 0.05). It is concluded that conditioning with the exercise types used had small effects. This could have been because the exercise stress was too small, but also because the workload was not increased during the CDP. Key words: alanine, blood, conditioning, exercise, horse, lactate