Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis

BACKGROUND Brain-derived neurotrophic factor (BDNF) blocks activation of caspase-3, reduces translocation of apoptosis-inducing factor (AIF), attenuates excitotoxicity of glutamate, and increases antioxidant enzyme activities. The mechanisms of neuroprotection suggest that BDNF may be beneficial in bacterial meningitis. METHODS To assess a potentially beneficial effect of adjuvant treatment with BDNF in bacterial meningitis, 11-day-old infant rats with experimental meningitis due to Streptococcus pneumoniae or group B streptococci (GBS) were randomly assigned to receive intracisternal injections with either BDNF (3 mg/kg) or equal volumes (10 mu L) of saline. Twenty-two hours after infection, brains were analyzed, by histomorphometrical examination, for the extent of cortical and hippocampal neuronal injury. RESULTS Compared with treatment with saline, treatment with BDNF significantly reduced the extent of 3 distinct forms of brain cell injury in this disease model: cortical necrosis in meningitis due to GBS (median, 0.0% [range, 0.0%-33.7%] vs. 21.3% [range, 0.0%-55.3%]; P<.03), caspase-3-dependent cell death in meningitis due to S. pneumoniae (median score, 0.33 [range, 0.0-1.0] vs. 1.10 [0.10-1.56]; P<.05), and caspase-3-independent hippocampal cell death in meningitis due to GBS (median score, 0 [range, 0-2] vs. 0.88 [range, 0-3.25]; P<.02). The last form of injury was associated with nuclear translocation of AIF. CONCLUSION BDNF efficiently reduces multiple forms of neuronal injury in bacterial meningitis and may hold promise as adjunctive therapy for this disease.

Bacterial meningitis causes two distinct forms of cellular damage in the hippocampal dentate gyrus in infant rats.

Bacterial meningitis causes neurological sequelae in up to 50% of survivors. Two pathogens known for their propensity to cause severe neurological damage are Streptococcus pneumoniae and group B streptococci. Some forms of neuronal sequelae, such as learning and memory deficits, have been associated with neuronal injury in the hippocampus. To learn more about hippocampal injury in meningitis, we performed a comparative study in bacterial meningitis due to S. pneumoniae and group B streptococcus, in which 11-day-old infant rats were infected intracisternally with either of the two pathogens. Histopathological examination of the neuronal injury in the dentate gyrus of the hippocampus showed that S. pneumoniae caused predominantly classical apoptotic cell death. Cells undergoing apoptosis were located only in the subgranular zone and stained positive for activated caspase-3 and TUNEL. Furthermore, dividing progenitor cells seemed particularly sensitive to this form of cell death. Group B streptococcus was mainly responsible for a caspase-3-independent (and TUNEL-negative) form of cell death. Compared with the morphological features found in apoptosis (e.g., apoptotic bodies), this form of neuronal death was characterized by clusters of uniformly shrunken cells. It affected the dentate gyrus throughout the blade, showing no preferences for immature or mature neurons. Thus, depending on the infecting agent, bacterial meningitis causes two distinct forms of cell injury in the dentate gyrus.

The history of the Jews, from the taking of Jerusalem by Titus, to the present time, comprising a narrative of their wanderings, persecutions, commercial enterprises, literature, manners, customs, and forms of worship : with an account of the various efforts made for their conversion

[James A. Huie]

Proof internalization in generalized Frege systems for classical logic

We present a general method for inserting proofs in Frege systems for classical logic that produces systems that can internalize their own proofs.

Censors for Boolean Description Logic

Protecting different kinds of information has become an important area of research. One aspect is to provide effective means to avoid that secrets can be deduced from the answers of legitimate queries. In the context of atomic propositional databases several methods have been developed to achieve this goal. However, in those databases it is not possible to formalize structural information. Also they are quite restrictive with respect to the specification of secrets. In this paper we extend those methods to match the much greater expressive power of Boolean description logics. In addition to the formal framework, we provide a discussion of various kinds of censors and establish different levels of security they can provide.

Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending on the inflammatory microenvironment

FcαRI (CD89), the human Fc receptor for IgA, is highly expressed on neutrophil granulocytes. In this study, we show that FcαRI induces different forms of neutrophil death, depending on the inflammatory microenvironment. The susceptibility of inflammatory neutrophils from sepsis or rheumatoid arthritis toward death induced by specific mAb, or soluble IgA at high concentrations, was enhanced. Although unstimulated cells experienced apoptosis following anti-FcαRI mAb stimulation, preactivation with cytokines or TLR agonists in vitro enhanced FcαRI-mediated death by additional recruitment of caspase-independent pathways, but this required PI3K class IA and MAPK signaling. Transmission electron microscopy of FcαRI-stimulated cells revealed cytoplasmic changes with vacuolization and mitochondrial swelling, nuclear condensation, and sustained plasma membrane. Coculture experiments with macrophages revealed anti-inflammatory effects of the partially caspase-independent death of primed cells following FcαRI engagement. Our data suggest that FcαRI has the ability to regulate neutrophil viability and to induce different forms of neutrophils depending on the inflammatory microenvironment and specific characteristics of the ligand-receptor interactions. Furthermore, these findings have potential implications for FcαRI-targeted strategies to treat neutrophil-associated inflammatory diseases.

Professionalisation of sport federations. A multi-level framework for analysing forms, causes and consequences

Research question: International and national sport federations as well as their member organisations (usually sport clubs) are key actors within the sport system and have a wide range of relationships outside the sport system (e.g. with the state, sponsors, and the media). They are currently facing major challenges such as growing competition in top-level sports, democratisation of sports with “sports for all” and sports as the answer to social problems (integration, education, health, unemployment, etc.). In this context, professionalising sport organisations seems to be an appropriate strategy to face these challenges and solve current problems. We define the professionalisation of sport organisations as an organisational process of transformation leading towards organisational rationalisation, efficiency and business-like management. This has led to a profound organisational change, particularly within sport federations, characterised by the strengthening of institutional management (managerialism) and the implementation of efficiency-based management instruments and paid staff. Research methods: The goal of this article is to review the international literature and establish a global understanding of and theoretical framework for how sport organisations professionalise and what consequences this may have. Results and Findings: Our multi-level approach based on the social theory of action integrates the current concepts for analysing professionalisation in sport federations. We specify the framework for the following research perspectives: (1) forms, (2) causes and (3) consequences, and discuss the reciprocal relations between sport federations and their member organisations in this context. Implications: Finally, we derive general methodological consequences for the investigation of professionalisation processes in sport organisations.

Just Reading? How Gender-Fair Language Triggers Readers' Use of Gender-Fair Forms

Gender-fair language, that is, referring to men and women with symmetrical linguistic forms, has been found to promote gender equality, but it is largely unknown which factors help make gender-fair forms more common in everyday life. Two studies examined whether speakers of German used more gender-fair forms after reading a text with gender-fair wording (vs. masculine generics vs. no personal nouns vs. another topic). Both studies showed consistently that women used more gender-fair forms after reading the gender-fair text than the other texts, whereas men did not. Men employed more gender-fair forms only after being made aware of these forms (Study 2). To conclude, merely reading gender-fair texts enhances women’s inclination to use gender-fair language, whereas men need to be made aware of this type of language use. Both studies highlight the importance of using gender-fair language frequently and consistently in everyday life.