Effect of a cognitive training program on the platelet app ratio in patients with alzheimer’s disease

In patients with Alzheimer’s disease (AD), synaptic plasticity seems to be involved in cognitive improvement induced by cognitive training. The platelet amyloid precursor protein (APP) ratio (APPr), i.e., the ratio between two APP isoforms, may be a useful peripheral biomarker to investigate synaptic plasticity pathways. This study evaluates the changes in neuropsychological/cognitive performance and APPr induced by cognitive training in AD patients participating in the “My Mind Project”. Neuropsychological/cognitive variables and APPr were evaluated in the trained group (n = 28) before a two-month experimental protocol, immediately after its termination at follow-up 1 (FU1), after 6 months at follow-up 2 (FU2), and after 24 months at follow-up 3 (FU3). The control group (n = 31) received general psychoeducational training for two months. Some memory and attention parameters were significantly improved in trained vs. control patients at FU1 and FU2 compared to baseline (∆ values). At FU3, APPr and Mini Mental State Examination (MMSE) scores decreased in trained patients. ∆ APPr correlated significantly with the ∆ scores of (i) MMSE at FU1, (ii) the prose memory test at FU2, and (iii) Instrumental Activities of Daily Living (IADL), the semantic word fluency test, Clinical Dementia Rating (CDR), and the attentive matrices test at FU3. Our data demonstrate that the platelet APPr correlates with key clinical variables, thereby proving that it may be a reliable biomarker of brain function in AD patients

How to Create an Innovation Accelerator

Too many policy failures are fundamentally failures of knowledge. This has become particularly apparent during the recent financial and economic crisis, which is questioning the validity of mainstream scholarly paradigms. We propose to pursue a multi-disciplinary approach and to establish new institutional settings which remove or reduce obstacles impeding efficient knowledge creation. We provided suggestions on (i) how to modernize and improve the academic publication system, and (ii) how to support scientific coordination, communication, and co-creation in large-scale multi-disciplinary projects. Both constitute important elements of what we envision to be a novel ICT infrastructure called "Innovation Accelerator" or "Knowledge Accelerator".Comment: 32 pages, Visioneer White Paper, see http://www.visioneer.ethz.c

From Social Data Mining to Forecasting Socio-Economic Crisis

Socio-economic data mining has a great potential in terms of gaining a better understanding of problems that our economy and society are facing, such as financial instability, shortages of resources, or conflicts. Without large-scale data mining, progress in these areas seems hard or impossible. Therefore, a suitable, distributed data mining infrastructure and research centers should be built in Europe. It also appears appropriate to build a network of Crisis Observatories. They can be imagined as laboratories devoted to the gathering and processing of enormous volumes of data on both natural systems such as the Earth and its ecosystem, as well as on human techno-socio-economic systems, so as to gain early warnings of impending events. Reality mining provides the chance to adapt more quickly and more accurately to changing situations. Further opportunities arise by individually customized services, which however should be provided in a privacy-respecting way. This requires the development of novel ICT (such as a self- organizing Web), but most likely new legal regulations and suitable institutions as well. As long as such regulations are lacking on a world-wide scale, it is in the public interest that scientists explore what can be done with the huge data available. Big data do have the potential to change or even threaten democratic societies. The same applies to sudden and large-scale failures of ICT systems. Therefore, dealing with data must be done with a large degree of responsibility and care. Self-interests of individuals, companies or institutions have limits, where the public interest is affected, and public interest is not a sufficient justification to violate human rights of individuals. Privacy is a high good, as confidentiality is, and damaging it would have serious side effects for society.Comment: 65 pages, 1 figure, Visioneer White Paper, see http://www.visioneer.ethz.c

The Mechanism of Antifungal Action of Essential Oil from Dill (Anethum graveolens L.) on Aspergillus flavus

The essential oil extracted from the seeds of dill (Anethum graveolens L.) was demonstrated in this study as a potential source of an eco-friendly antifungal agent. To elucidate the mechanism of the antifungal action further, the effect of the essential oil on the plasma membrane and mitochondria of Aspergillus flavus was investigated. The lesion in the plasma membrane was detected through flow cytometry and further verified through the inhibition of ergosterol synthesis. The essential oil caused morphological changes in the cells of A. flavus and a reduction in the ergosterol quantity. Moreover, mitochondrial membrane potential (MMP), acidification of external medium, and mitochondrial ATPase and dehydrogenase activities were detected. The reactive oxygen species (ROS) accumulation was also examined through fluorometric assay. Exposure to dill oil resulted in an elevation of MMP, and in the suppression of the glucose-induced decrease in external pH at 4 µl/ml. Decreased ATPase and dehydrogenase activities in A. flavus cells were also observed in a dose-dependent manner. The above dysfunctions of the mitochondria caused ROS accumulation in A. flavus. A reduction in cell viability was prevented through the addition of L-cysteine, which indicates that ROS is an important mediator of the antifungal action of dill oil. In summary, the antifungal activity of dill oil results from its ability to disrupt the permeability barrier of the plasma membrane and from the mitochondrial dysfunction-induced ROS accumulation in A. flavus

Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease

In aged rats, differences in spatial learning and memory influence the response to late-life Environmental Enrichment - Balietti et al., 2021

Below the abstract of the manuscript in which data were described: "It has clearly been demonstrated that cognitive stimulation, physical exercise, and social engagement help counteract age-related cognitive decline. However, several important issues remain to be addressed. Given the wide differences in cognitive impairment found among individuals of the same age, identifying the subjects who will benefit most from late-life interventions is one such issue. Environmental Enrichment (EE) is a particularly valuable approach to do this. In this study, aged (21-month-old) rats were assigned to a better (BL) or a worse (WL) learner group (training phase) and to a non-impaired (NI) or an impaired (I) group (probe phase) by their performance on the Morris Water Maze, using the test performances of adult (12-month-old) rats as the cut-offs. The aged rats were retested after a 12-week EE or standard housing (SH) protocol. After 12 weeks, the performances of SH rats had deteriorated, whereas all rats benefited from EE, albeit in different ways. In particular, the animals assigned to the BL and the NI groups prior to EE still performed as well as the adult rats (performance preservation) whereas, critically, the animals assigned to the WL and the I groups before EE showed such improved performances that they reached the level of the adult rats (performance improvement), despite having aged further. EE seems to induce the preservation in BLs and the improvement in WLs of spatial search strategies and the preservation in NIs and the increase in Is of a focused and protract research of the escape point. Our findings suggest that late-life EE prevents spatial learning and memory decline in still cognitively preserved animals and stimulates residual functional reserve in already cognitively compromised animals. Future research should focus on individually tailored stimulation protocols to improve their effect and afford a better understanding of the underlying processes." For using data set, please cite: https://doi.org/10.1016/j.exger.2020.11122

Aged rats with different performances at environmental enrichment onset display different modulation of habituation and aversive memory

A wide agreement exists that environmental enrichment (EE) is most beneficial if introduced early in life, but numerous studies reported that also aged animals remain responsive. As age-related memory and cognition impairments are not uniform, an open question is whether EE might exert different effects in animals with different age-related deficits. A 12-week EE protocol was applied to late adult rats pretested for habituation and aversive memory. Animals were classified as low (LP) and high (HP) performers according to percent exploration change in Open Field test (OF) and as impaired (I) and not impaired (NI) according to latency in Step-through Passive Avoidance test (PA). Standard housing (SH) animals pretested by OF and PA, and naïve (non-pretested) EE and SH rats were used as controls. In comparison to pretest, after the housing protocol, EE LP ameliorated while EE HP and both SH HP and LP worsened their habituation pattern. The positive influence of EE on LP was probably due to the more active interaction with and the faster adaptation to surroundings promoted by continuous, multiple stimuli provided during the enriched housing. Regarding HP, EE did not boost the basal behavior, which likely represented the maximum achievable for that age, and the post housing exploration change dropped, as in SH animals, because of the retesting. After EE, a significant percentage of NI animals became I and a significant percentage of I animals became NI. The changes evidenced in the NI group likely depended on EE-related reduction of anxiety and the consequent more efficient coping with fearful situations. This hypothesis was strengthened by the observation that naïve EE animals were almost all I. Pretested EE I rats were not influenced by the rearing condition: their behavior was comparable to SH animals’ behavior and determined by retesting. In conclusion, these results demonstrated that, when applied to aging rats, EE produces different effects based on pre-housing cognitive performances. The issue needs further analyses, but the observation that not all animals are able to take advantage of EE to the same extent suggests the opportunity to design individually tailored approaches to optimize their efficacy and minimize possible unwanted consequences

Perichromatin fibrils accumulation in hepatocyte nuclei reveals alterations of pre-mRNA processing during ageing.

We previously described an unusual accumulation of perichromatin fibrils (PF)\u2014the in situ form of pre-mRNA transcription and early splicing\u2014in hepatocyte nuclei of old rats. Here we have investigated, by immunoelectron microscopy, the nature of such PF, analyzing the presence of transcription, splicing and cleavage factors, polyadenylated RNA, and the incorporation of bromouridine in adult and old rats. Our observations revealed alterations in amount and/or distribution of pre-mRNA transcription, splicing and cleavage factors, as well as of polyadenylated RNA, together with lower bromouridine incorporation in newly transcribed RNA in the hepatocyte nucleoplasm of old rats. Therefore, our data indicate both a decrease in pre-mRNA transcription and a slow down of PF processing and transport during aging