Nonlinear maternal effects on personality in a rodent species with fluctuating densities

Consistent among-individual variation in behavior, or animal personality, is present in a wide variety of species. This behavioral variation is maintained by both genetic and environmental factors. Parental effects are a special case of environmental variation and are expected to evolve in populations experiencing large fluctuations in their environment. They represent a non-genetic pathway by which parents can transmit information to their offspring, by modulating their personality. While it is expected that parental effects contribute to the observed personality variation, this has rarely been studied in wild populations. We used the multimammate mouse Mastomys natalensis as a model system to investigate the potential effects of maternal personality on offspring behavior. We did this by repeatedly recording the behavior of individually housed juveniles which were born and raised in the lab from wild caught females. A linear correlation, between mother and offspring in behavior, would be expected when the personality is only affected by additive genetic variation, while a more complex relationship would suggests the presence of maternal effects. We found that the personality of the mother predicted the behavior of their offspring in a non-linear pattern. Exploration behavior of mother and offspring was positively correlated, but only for slow and average exploring mothers, while this correlation became negative for fast exploring mothers. This may suggests that early maternal effects could affect personality in juvenile M. natalensis, potentially due to density-dependent and negative frequency-dependent mechanisms, and therefore contribute to the maintenance of personality variation

Numerical model for the determination of the reduced electric field in a CO\u3csub\u3e2\u3c/sub\u3e microwave plasma derived by the principle of impedance matching

\u3cp\u3eThree dimensional electromagnetic modelling of a free-standing CO\u3csub\u3e2\u3c/sub\u3e microwave plasma has been performed, by describing the plasma as a dielectric medium. The relative permittivity and conductivity of the medium are parametrised. The waveguide geometry from the experiment, including the tuner, is put into the model, knowing that this corresponds to maximum power transfer of the microwave generator to the plasma under plasma impedance matching conditions. Two CO\u3csub\u3e2\u3c/sub\u3e plasma discharge regimes, differing mainly in pressure, input power and temperature, have been studied. The model's validity has been checked through study of materials of known conductivity. From measurements of the neutral gas temperature and the plasma electron density profile, the reduced electric field is determined. From the parametrisation of the dielectric properties, a range for the effective electron-neutral collision frequency for momentum transfer is estimated. The results for the reduced electric field and the range of the electron neutral collision frequency obtained, are consistent as verified by simulations using BOLSIG+. In addition, from this comparison it is possible to narrow down the range of the collision frequencies, and to estimate the electron temperature. The reduced electric field lies between 80 and 180 Td for the relatively low pressure, low input power, the so-called 'diffuse' regime. For the relatively high pressure, high input power ('contracted') regime it lies between 10 and 60 Td. The normalised collision frequency lies between 1.6 and 2.3 for the diffuse regime, while for the contracted regime it lies between 2 and 3. The electron temperature ranges from 2 to 3 eV for the diffuse regime, and from 0.5 to 1 eV for the contracted regime.\u3c/p\u3

Utilization of fluid-based biomarkers as endpoints in disease-modifying clinical trials for Alzheimer’s disease: a systematic review

Abstract Background Clinical trials in Alzheimer’s disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development. Methods We systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01–01-2017 and 01–01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type. Results We found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers. Conclusions As the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets

Additional file 1 of The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease

Additional file 1: Supplementary Figure 1. Correlation matrix of the fluid biomarkers to cognitive test performance and social test scores in patients with bvFTD, PPD, AD, and controls. The associations are shown as Pearson’s partial correlations, controlling for age. bvFTD: behavioral variant frontotemporal dementia, PPD: primary psychiatric disorders, AD: Alzheimer’s disease, NfL: neurofilament light, SNAP25: synaptosomal associated protein 25, Ng: neurogranin, NPTX2: neuronal pentraxin 2, GluR4: Glutamate receptor 4, MMSE: mini-mental state examination, FTLD-CDR: frontotemporal lobe dementia- cognitive dementia rating. Panel bvFTD_PPD: NfL, NPTX2, Panel bvFTD_AD: NfL, SNAP25, Ng, GluR4 (both differential diagnostic panels selected using backward logistic regression models).*p <0.05, **p <0.01, ***p <0.00