Comparative Pathogenicity of Aeromonas spp. in Cultured Red Hybrid Tilapia (Oreochromis niloticus × O. mossambicus)

The genus Aeromonas has been recognised as an important pathogenic species in aquaculture that causes motile Aeromonas septicaemia (MAS) or less severe, chronic infections. This study compares the pathogenicity of the different Aeromonas spp. that were previously isolated from freshwater fish with signs of MAS. A total of 124 isolates of Aeromonas spp. were initially screened for the ability to grow on M9 agar with myo-inositol as a sole carbon source, which is a discriminatory phenotype for the hypervirulent A. hydrophila (vAh) pathotype. Subsequently, LD50 of six selected Aeromonas spp. were determined by intraperitoneal injection of bacterial suspension containing 103, 105, and 107 CFU/mL of the respective Aeromonas sp. to red hybrid tilapias. The kidneys, livers and spleens of infected moribund fish were examined for histopathological changes. The screening revealed that only A. dhakensis 1P11S3 was able to grow using myo-inositol as a sole carbon source, and no vAh strains were identified. The LD50–240h of A. dhakensis 1P11S3 was 107 CFU/mL, while the non-myo-inositol utilizing A. dhakensis 4PS2 and A. hydrophila 8TK3 was lower at 105 CFU/mL. Similarly, tilapia challenged with the myo-inositol A. dhakensis 1P11S3 showed significantly (p < 0.05) less severe signs, gross and histopathological lesions, and a lower mortality rate than the non-myo-inositol A. dhakensis 4PS2 and A. hydrophila 8TK3. These findings suggested that myo-inositol utilizing A. dhakensis 1P11S3 was not a hypervirulent Aeromonas sp. under current experimental disease challenge conditions, and that diverse Aeromonas spp. are of concern in aquaculture farmed freshwater fish. Therefore, future study is warranted on genomic level to further elucidate the influence of myo-inositol utilizing ability on the pathogenesis of Aeromonas spp., since this ability correlates with hypervirulence in A. hydrophila strains.

The role of complex IV activity in the axonal response of mitochondria to demyelination in experimental disease models of multiple sclerosis

Axon loss is a cardinal neuropathological feature of multiple sclerosis (MS). Axonal injury in MS and experimental disease models is most frequently detected in acutely demyelinating regions. Furthermore, acute axonal injury consistently correlates with the extent of inflammatory demyelination. Following lysolecithin-induced demyelination, we recently reported a compensatory response in neurons, where mitochondria move from the cell body to the acutely demyelinated axon and increase the mitochondrial content. We termed this energetics phenomenon, that is also evident in MS, the axonal response of mitochondria to demyelination (ARMD). In the present study, we assessed axonal mitochondrial content as well as axonal mitochondrial respiratory chain complex IV activity (COX) of axons and related these to axonal injury in nine different experimental disease models. We consistently found ARMD in all experimental disease models. However, the increase in mitochondrial content within demyelinated axons was not always accompanied by a proportionate increase in COX activity, particularly in experimental autoimmune encephalomyelitis (EAE). Axonal COX activity inversely correlated with the extent of axonal injury in experimental disease models. Our findings indicate that ARMD is a consistent and prominent finding and emphasises the need to preserve axonal mitochondrial COX activity in inflammatory demyelination, paving the way for the development of novel neuroprotective therapies.

Tracing Neurological Diseases in the Presymptomatic Phase: Insights From Neurofilament Light Chain

The identification of neurological diseases in their presymptomatic phase will be a fundamental aim in the coming years. This step is necessary both to optimize early diagnostics and to verify the effectiveness of experimental disease modifying drugs in the early stages of diseases. Among the biomarkers that can detect neurological diseases already in their preclinical phase, neurofilament light chain (NfL) has given the most promising results. Recently, its measurement in serum has enabled the identification of neurodegeneration in diseases such as multiple sclerosis (MS) and Alzheimer’s disease (AD) up to 6–10 years before the onset of symptoms. Similar results have been obtained in conditions such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), up to 2 years before clinical onset. Study of the longitudinal dynamics of serum NfL has also revealed interesting aspects of the pathophysiology of these diseases in the preclinical phase. This review sought to discuss these very recent findings on serum NfL in the presymptomatic phase of neurological diseases.

The Impact of the Covid-19 Pandemic on Disgust Sensitivity

There have been few tests of whether exposure to naturalistic or experimental disease-threat inductions alter disgust sensitivity, although it has been hypothesized that this should occur as part of disgust’s disease avoidance function. In the current study, we asked Macquarie university students to complete measures of disgust sensitivity, perceived vulnerability to disease (PVD), hand hygiene behavior and impulsivity, during Australia’s Covid-19 pandemic self-quarantine (lockdown) period, in March/April 2020. These data were then compared to earlier Macquarie university, and other local, and overseas student cohorts, to determine if disgust sensitivity and the other measures, were different in the lockdown sample. The most consistent finding in the lockdown sample was of higher core disgust sensitivity (Cohen’s d = 0.4), with some evidence of greater germ aversion on the PVD, and an increase in hand and food-related hygiene, but with little change in impulsivity. The consistency with which greater core disgust sensitivity was observed, suggests exposure to a highly naturalistic disease threat is a plausible cause. Greater disgust sensitivity may have several functional benefits (e.g., hand and food-related hygiene) and may arise implicitly from the threat posed by the Covid-19 pandemic.

LifeTime and improving European healthcare through cell-based interceptive medicine

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.

A Commercial Probiotic Induces Tolerogenic and Reduces Pathogenic Responses in Experimental Autoimmune Encephalomyelitis

Previous studies in experimental autoimmune encephalomyelitis (EAE) models have shown that some probiotic bacteria beneficially impact the development of this experimental disease. Here, we tested the therapeutic effect of two commercial multispecies probiotics—Lactibiane iki and Vivomixx—on the clinical outcome of established EAE. Lactibiane iki improves EAE clinical outcome in a dose-dependent manner and decreases central nervous system (CNS) demyelination and inflammation. This clinical improvement is related to the inhibition of pro-inflammatory and the stimulation of immunoregulatory mechanisms in the periphery. Moreover, both probiotics modulate the number and phenotype of dendritic cells (DCs). Specifically, Lactibiane iki promotes an immature, tolerogenic phenotype of DCs that can directly induce immune tolerance in the periphery, while Vivomixx decreases the percentage of DCs expressing co-stimulatory molecules. Finally, gut microbiome analysis reveals an altered microbiome composition related to clinical condition and disease progression. This is the first preclinical assay that demonstrates that a commercial probiotic performs a beneficial and dose-dependent effect in EAE mice and one of the few that demonstrates a therapeutic effect once the experimental disease is established. Because this probiotic is already available for clinical trials, further studies are being planned to explore its therapeutic potential in multiple sclerosis patients.

GSK3: A Kinase Balancing Promotion and Resolution of Inflammation

GSK3 has been implicated for years in the regulation of inflammation and addressed in a plethora of scientific reports using a variety of experimental (disease) models and approaches. However, the specific role of GSK3 in the inflammatory process is still not fully understood and controversially discussed. Following a detailed overview of structure, function, and various regulatory levels, this review focusses on the immunoregulatory functions of GSK3, including the current knowledge obtained from animal models. Its impact on pro-inflammatory cytokine/chemokine profiles, bacterial/viral infections, and the modulation of associated pro-inflammatory transcriptional and signaling pathways is discussed. Moreover, GSK3 contributes to the resolution of inflammation on multiple levels, e.g., via the regulation of pro-resolving mediators, the clearance of apoptotic immune cells, and tissue repair processes. The influence of GSK3 on the development of different forms of stimulation tolerance is also addressed. Collectively, the role of GSK3 as a kinase balancing the initiation/perpetuation and the amelioration/resolution of inflammation is highlighted.