Preoperative detection of the postoperative risk thromboembolism. Results of a prospective study. IV. Thrombocyte parameters

Some platelet properties determined preoperatively in the course of a prospective clinical study show significant differences between the patient groups with and without DVT after total hip replacement. None of the platelet tests alone is indicative of the development of DVT.     

Cuticular hydrocarbons as potential mediators of cryptic species divergence in a mutualistic ant association

Upon advances in sequencing techniques, more and more morphologically identical organisms are identified as cryptic species. Often, mutualistic interactions are proposed as drivers of diversification. Species of the neotropical parabiotic ant association between Crematogaster levior and Camponotus femoratus are known for highly diverse cuticular hydrocarbon (CHC) profiles, which in insects serve as desiccation barrier but also as communication cues. In the present study, we investigated the association of the ants’ CHC profiles with genotypes and morphological traits, and discovered cryptic species pairs in both genera. To assess putative niche differentiation between the cryptic species, we conducted an environmental association study that included various climate variables, canopy cover, and mutualistic plant species. Although mostly sympatric, the two Camponotus species seem to prefer different climate niches. However in the two Crematogaster species, we could not detect any differences in niche preference. The strong differentiation in the CHC profiles may thus suggest a possible role during speciation itself either by inducing assortative mating or by reinforcing sexual selection after the speciation event. We did not detect any further niche differences in the environmental parameters tested. Thus, it remains open how the cryptic species avoid competitive exclusion, with scope for further investigations.     

In vitro study of platelet concentrate preparations from whole blood using N-(2-mercaptopropionyl)-glycine

The sulfhydryl group containing drug N-(2-mercaptopropionyl)-glycine (MPG) which inhibits platelet aggregation in a reversible manner permits to prepare platelet concentrates in non-siliconized glass containers at pH 7.4. Resuspension of platelets is possible immediately after centrifugation. In vitro platelets tests were carried out after washing out the MPG in MPG-free plasma. Thereafter, no inhibitory effects on platelet functions were found. Platelets concentrated in presence of MPG were significantly better with respect to yield, maintenance of discoid shape, aggregability, and hypotonic shock response compared with control platelets concentrated in absence of MPG.     

The role of the actin status in platelet behaviour

The status of platelet actin has been studied analytically by the DNase-I inhibition assay. Exposure of platelets to diamide, which oxidizes sulphydryl groups, results in an increase of filamentous actin. Neutralization of the effect of diamide by addition of 2-mercaptopropionylglycine (2-MPG) or washing out the excess of diamide is associated with a normalization of the cellular actin status. These findings strongly suggest that the redox state of platelets is somehow involved in the process of actin polymerization. Alterations of the redox state in metabolically altered platelets could therefore account for changes in the G- to F-actin equilibrium. In the thrombin-induced actin polymerization the redox state of the cell seems to be not involved, since 2-MPG preincubation of platelets (1.25 mM, 30 min) does not inhibit the filament assembly.     

Essentiality of c-di-AMP in Bacillus subtilis: Bypassing mutations converge in potassium and glutamate homeostasis

In order to adjust to changing environmental conditions, bacteria use nucleotide second messengers to transduce external signals and translate them into a specific cellular response. Cyclic di-adenosine monophosphate (c-di-AMP) is the only known essential nucleotide second messenger. In addition to the well-established role of this second messenger in the control of potassium homeostasis, we observed that glutamate is as toxic as potassium for a c-di-AMP-free strain of the Gram-positive model bacterium Bacillus subtilis. In this work, we isolated suppressor mutants that allow growth of a c-di-AMP-free strain under these toxic conditions. Characterization of glutamate resistant suppressors revealed that they contain pairs of mutations, in most cases affecting glutamate and potassium homeostasis. Among these mutations, several independent mutations affected a novel glutamate transporter, AimA (Amino acid importer A, formerly YbeC). This protein is the major transporter for glutamate and serine in B. subtilis. Unexpectedly, some of the isolated suppressor mutants could suppress glutamate toxicity by a combination of mutations that affect phospholipid biosynthesis and a specific gain-of-function mutation of a mechanosensitive channel of small conductance (YfkC) resulting in the acquisition of a device for glutamate export. Cultivation of the c-di-AMP-free strain on complex medium was an even greater challenge because the amounts of potassium, glutamate, and other osmolytes are substantially higher than in minimal medium. Suppressor mutants viable on complex medium could only be isolated under anaerobic conditions if one of the two c-di-AMP receptor proteins, DarA or DarB, was absent. Also on complex medium, potassium and osmolyte toxicity are the major bottlenecks for the growth of B. subtilis in the absence of c-di-AMP. Our results indicate that the essentiality of c-di-AMP in B. subtilis is caused by the global impact of the second messenger nucleotide on different aspects of cellular physiology.     

Transient Improvement of Cerebellar Oligodendroglial Development in a Neonatal Hyperoxia Model by PDGFA Treatment

In preterm infants, the changes from fetal life to ex‐utero conditions often coincide with reduced growth and white matter damage of the cerebellum. The premature increase in arterial oxygen tension caused by preterm birth may dysregulate cerebellar development. In a hyperoxia rat model of white matter damage to mimic a steep increase in oxygen levels by 24 h exposure to 80% O₂ from postnatal day 6 (P6) to day 7, we analyzed growth factor (GF) synthesis of cerebellar astrocytes. Determination of GF production was performed in astrocytes after Magnetic‐activated cell sorting (MACS) isolation from cerebelli after hyperoxia exposure ex vivo, and also in astroglial cultures. Oligodendrocyte progenitor cell (OPC) function was analyzed in cerebellar OPCs isolated by MACS after hyperoxia. Administration of PDGFA from P6 to P11, during hyperoxia and during 4 days recovery, was finally tested for protection of oligodendroglia and myelination. As a result, expression of the GFs Pdgfa, Fgf2, and Bdnf was diminished in cerebellar astrocytes in vitro and in vivo. Gene expression of Olig1, Olig2, Sox9, Sox10, and Cnp was reduced in OPCs in vivo. Nasal PDGFA application improved oligodendroglial proliferation after hyperoxia at P7. However, this treatment effect vanished until P9. Impaired MBP expression after hyperoxia was attenuated by PDGFA treatment until P11, but not beyond when PDGFA supply was stopped. In this study on neonatal cerebellar injury, it is documented for the first time that improvement of oligodendroglial proliferation and of myelination can be achieved by PDGFA treatment. However, the treatment benefit is not maintained long term.     

HIV Treatment as Prevention: Issues in Economic Evaluation

Meyer-Rath and Over assert in another article in the July 2012 PLoS Medicine Collection, “Investigating the Impact of Treatment on New HIV Infections”, that economic evaluations of antiretroviral therapy (ART) in currently existing programs and in HIV treatment as prevention (TasP) programs should use cost functions that capture cost dependence on a number of factors, such as scale and scope of delivery, health states, ART regimens, health workers'' experience, patients'' time on treatment, and the distribution of delivery across public and private sectors. We argue that for particular evaluation purposes (e.g., to establish the social value of TasP) and from particular perspectives (e.g., national health policy makers) less detailed cost functions may be sufficient. We then extend the discussion of economic evaluation of TasP, describing why ART outcomes and costs assessed in currently existing programs are unlikely to be generalizable to TasP programs for several fundamental reasons. First, to achieve frequent, widespread HIV testing and high uptake of ART immediately following an HIV diagnosis, TasP programs will require components that are not present in current ART programs and whose costs are not included in current estimates. Second, the early initiation of ART under TasP will change not only patients'' disease courses and treatment experiences—which can affect behaviors that determine clinical treatment success, such as ART adherence and retention—but also quality of life and economic outcomes for HIV-infected individuals. Third, the preventive effects of TasP are likely to alter the composition of the HIV-infected population over time, changing its biological and behavioral characteristics and leading to different costs and outcomes for ART.