Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Enhancements Are Blackbox Non-Trivial: Impossibility of Enhanced Trapdoor Permutations from Standard Trapdoor Permutations

Trapdoor permutations (TDP) are a fundamental primitive in cryptography. Over the years, several variants of this notion have emerged as a result of various applications. However, it is not clear whether these variants may be based on the standard notion of TDPs. We study the question of whether enhanced trapdoor permutations can be based on classical trapdoor permutations. The main motivation of our work is in the context of existing TDP-based constructions of oblivious transfer and non-interactive zero-knowledge protocols, which require enhancements to the classical TDP notion. We prove that these enhancements are non-trivial, in the sense that there does not exist fully blackbox constructions of enhanced TDPs from classical TDPs. At a technical level, we show that the enhanced TDP security of any construction in the random TDP oracle world can be broken via a polynomial number of queries to the TDP oracle as well as a weakening oracle, which provides inversion with respect to randomness. We also show that the standard one-wayness of a random TDP oracle stays intact in the presence of this weakening oracle

Memory Lower Bounds of Reductions Revisited

In Crypto 2017, Auerbach et al. initiated the study on memory-tight reductions and proved two negative results on the memory-tightness of restricted black-box reductions from multi-challenge security to single-challenge security for signatures and an artificial hash function. In this paper, we revisit the results by Auerbach et al. and show that for a large class of reductions treating multi-challenge security, it is impossible to avoid loss of memory-tightness unless we sacrifice the efficiency of their running-time. Specifically, we show three lower bound results. Firstly, we show a memory lower bound of natural black-box reductions from the multi-challenge unforgeability of unique signatures to any computational assumption. Then we show a lower bound of restricted reductions from multi-challenge security to single-challenge security for a wide class of cryptographic primitives with unique keys in the multi-user setting. Finally, we extend the lower bound result shown by Auerbach et al. treating a hash function to one treating any hash function with a large domain

On the Security Loss of Unique Signatures

We consider the question of whether the security of unique digital signature schemes can be based on game-based cryptographic assumptions using linear-preserving black-box security reductions—that is, black-box reductions for which the security loss (i.e., the ratio between work of the adversary and the work of the reduction) is some a priori bounded polynomial. A seminal result by Coron (Eurocrypt\u2702) shows limitations of such reductions; however, his impossibility result and its subsequent extensions all suffer from two notable restrictions: (1) they only rule out so-called simple reductions, where the reduction is restricted to only sequentially invoke straight-line instances of the adversary; and (2) they only rule out reductions to non-interactive (two-round) assumptions. In this work, we present the first full impossibility result: our main result shows that the existence of any linear-preserving black-box reduction for basing the security of unique signatures on some bounded-round assumption implies that the assumption can be broken in polynomial time

Targeting neuroinflammation for therapeutic intervention in neurodegenerative pathologies: A role for the peptide analogue of thymulin (PAT)

Introduction: Inflammation has a vital task in protecting the organism, but when deregulated, it can have serious pathological consequences. The central nervous system (CNS) is capable of mounting immune and inflammatory responses, albeit different from that observed in the periphery. Neuroinflammation, however, can be a major contributor to neurodegenerative diseases and constitute a major challenge for medicine and basic research. Areas covered: Both innate and adaptive immune responses normally play an important role in homeostasis within the CNS. Microglia, astrocytes and neuronal cells express a wide array of toll-like receptors (TLR) that can be upregulated by infection, trauma, injuries and various exogenic or endogenic factors. Chronic hyper activation of brain immune cells can result in neurotoxic actions due to excessive production of several pro-inflammatory mediators. Several studies have recently described an important role for targeting receptors such as nicotinic receptors located on cells in the CNS or in other tissues for the control of inflammation. Expert opinion: Thymulin and its synthetic peptide analogue (PAT) appear to exert potent anti-inflammatory effects at the level of peripheral tissues as well as at the level of the brain. This effect involves, at least partially, the activation of cholinergic mechanisms. © 2012 Informa UK, Ltd

Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases

The central nervous system (CNS) is now known to actively communicate with the immune system to control immune responses both centrally and peripherally. Within the CNS, while studies on glial cells, especially microglia, have highlighted the importance of this cell type in innate immune responses of the CNS, the immune regulatory functions of other cell types, especially neurons, are largely unknown. How neuroimmune cross-talk is homeostatically maintained in neurodevelopment and adult plasticity is even more elusive. Inspiringly, accumulating evidence suggests that neurons may also actively participate in immune responses by controlling glial cells and infiltrated T cells. The potential clinical application of this knowledge warrants a deeper understanding of the mutual interactions between neurons and other types of cells during neurological and immunological processes within the CNS, which will help advance diagnosis, prevention, and intervention of various neurological diseases. The aim of this review is to address the immune function of both glial cells and neurons, and the roles they play in regulating inflammatory processes and maintaining homeostasis of the CNS.Peer reviewe

Reviewing the use of resilience concepts in forest sciences

Purpose of the review Resilience is a key concept to deal with an uncertain future in forestry. In recent years, it has received increasing attention from both research and practice. However, a common understanding of what resilience means in a forestry context, and how to operationalise it is lacking. Here, we conducted a systematic review of the recent forest science literature on resilience in the forestry context, synthesising how resilience is defined and assessed. Recent findings Based on a detailed review of 255 studies, we analysed how the concepts of engineering resilience, ecological resilience, and social-ecological resilience are used in forest sciences. A clear majority of the studies applied the concept of engineering resilience, quantifying resilience as the recovery time after a disturbance. The two most used indicators for engineering resilience were basal area increment and vegetation cover, whereas ecological resilience studies frequently focus on vegetation cover and tree density. In contrast, important social-ecological resilience indicators used in the literature are socio-economic diversity and stock of natural resources. In the context of global change, we expected an increase in studies adopting the more holistic social-ecological resilience concept, but this was not the observed trend. Summary Our analysis points to the nestedness of these three resilience concepts, suggesting that they are complementary rather than contradictory. It also means that the variety of resilience approaches does not need to be an obstacle for operationalisation of the concept. We provide guidance for choosing the most suitable resilience concept and indicators based on the management, disturbance and application context