Tau-related grey matter network breakdown across the Alzheimer’s disease continuum

Background Changes in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau-related connectivity changes across different stages of AD might be expected. We aimed to assess the relationship between tau aggregation and grey matter network alterations across the AD continuum. Methods We included 533 individuals (178 Aβ-negative cognitively unimpaired (CU) subjects, 105 Aβ-positive CU subjects, 122 Aβ-positive patients with mild cognitive impairment, and 128 patients with AD dementia) from the BioFINDER-2 study. Single-subject grey matter networks were extracted from T1-weighted images and graph theory properties including degree, clustering coefficient, path length, and small world topology were calculated. Associations between tau positron emission tomography (PET) values and global and regional network measures were examined using linear regression models adjusted for age, sex, and total intracranial volume. Finally, we tested whether the association of tau pathology with cognitive performance was mediated by grey matter network disruptions. Results Across the whole sample, we found that higher tau load in the temporal meta-ROI was associated with significant changes in degree, clustering, path length, and small world values (all p < 0.001), indicative of a less optimal network organisation. Already in CU Aβ-positive individuals associations between tau burden and lower clustering and path length were observed, whereas in advanced disease stages elevated tau pathology was progressively associated with more brain network abnormalities. Moreover, the association between higher tau load and lower cognitive performance was only partly mediated (9.3 to 9.5%) through small world topology. Conclusions Our data suggest a close relationship between grey matter network disruptions and tau pathology in individuals with abnormal amyloid. This might reflect a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions with tau pathology, indicative of a more random network topology across different AD stages.

Informal governance in the digital transformation

PurposeThe purpose of this study is to explore if and how informal governance mechanisms are used for coordinating actors of digitalized supply networks.Design/methodology/approachA multiple case study analysis of ten German firms in digitalized supply networks is conducted. Data are collected through semi-structured expert interviews with interviewees having notable years of professional experience in purchasing or sales.FindingsThis research shows that reduced personal contacts in digitalized supply networks decrease the ability to coordinate with informal governance mechanisms. However, the need for informal governance in digitalized supply networks remains when facing supply network disruptions or building new business relationships.Originality/valueThis is the first study examining the role of informal governance mechanisms in digitalized supply networks. Theoretical and practical insights on the changing abilities and needs to use informal governance after the digital transformation are given.

Basal ganglia-cerebellar and brainstem-cerebellar circuits may interact improperly with dystonia. Linking network disruptions to cell failure will enable understanding pathophysiology and designing gene therapy methods

From the preceding, it may be deduced that coupled dystonia syndromes are different, as are the disease phenotypes caused by the same gene. There are different starting ages, different symptom presentations, different disease manifestations, and atypical presentations. Accepting clinical exome sequencing and gene panels in the diagnosis of genetic diseases has also widened genotypes and phenotypes. It's critical to stay on top of the latest advances in genetic technology and to comprehend the full scope of these fascinating diseases. Online resources are updated on a regular basis and incorporate genetic and phenotypic data. Neurophysiology and imaging methods are important for better phenotyping and complementing clinical outcomes. Recent research suggests that the MYC/DYT-SGCE, XDP, and RDP basal ganglia-cerebellar and brainstem-cerebellar circuits may interact abnormally. Linking network interruptions to cellular failure will help us better grasp the underlying pathophysiology and teach us new treatment strategies.

Disrupted White Matter Networks from Subjective Memory Impairment to Amnestic Mild Cognitive Impairment

Background and Objective: Subjective memory impairment (SMI) is a preclinical stage prior to amnestic mild cognitive impairment (aMCI) along with the Alzheimer’s disease (AD) continuum. We hypothesized that SMI patients had white matter (WM) network disruptions similar to those in aMCI patients. Methods: We used diffusion-tensor magnetic resonance imaging and graph theory to construct, analyze, and compare the WM networks among 20 normal controls (NC), 20 SMI patients, and 20 aMCI patients. Results: Compared with the NC group, the SMI group had significantly decreased global and local efficiency and an increased shortest path length. Moreover, similar to the aMCI group, the SMI group had lower nodal efficiency in regions located in the frontal and parietal lobes, limbic systems, and caudate nucleus compared to that of the NC group. Conclusion: Similar to aMCI patient, SMI patients exhibited WM network disruptions, and detection of these disruptions could facilitate the early detection of SMI.

Vaccination strategies against COVID-19 and the diffusion of anti-vaccination views

Misinformation is usually adjusted to fit distinct narratives and propagates rapidly through social networks. False beliefs, once adopted, are rarely corrected. Amidst the COVID-19 crisis, pandemic-deniers and people who oppose wearing face masks or quarantine have already been a substantial aspect of the development of the pandemic. With the vaccine for COVID-19, different anti-vaccine narratives are being created and are probably being adopted by large population groups with critical consequences. Assuming full adherence to vaccine administration, we use a diffusion model to analyse epidemic spreading and the impact of different vaccination strategies, measured with the average years of life lost, in three network topologies (a proximity, a scale-free and a small-world network). Then, using a similar diffusion model, we consider the spread of anti-vaccine views in the network, which are adopted based on a persuasiveness parameter of anti-vaccine views. Results show that even if anti-vaccine narratives have a small persuasiveness, a large part of the population will be rapidly exposed to them. Assuming that all individuals are equally likely to adopt anti-vaccine views after being exposed, more central nodes in the network, which are more exposed to these views, are more likely to adopt them. Comparing years of life lost, anti-vaccine views could have a significant cost not only on those who share them, since the core social benefits of a limited vaccination strategy (reduction of susceptible hosts, network disruptions and slowing the spread of the disease) are substantially shortened.

Microbiota alterations in proline metabolism impact on depression through GABA and ECM homeostasis

The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including mild-depressed patients. Microbial functions and metabolites converging into glutamate/GABA metabolism, particularly proline, were linked to depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotional-impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related pre-frontal cortex genes. Targeting the microbiome and dietary proline may open new windows for an efficient depression treatment.

Problematika Dalam Pembelajaran Berbasis Virtual Learning Environment (VLE) Terhadap Siswa dan Guru SMA/MA Pada Materi Biologi Di Masa COVID-19

The research aims to find out the problem of Learning based on Virtual Learning Environment (VLE) for high school / MA students in biological materials in the COVID-19 era. This research is qualitative research with a fenomenology approach. Data collection techniques in research are observations, interviews, and questionnaires. The technique of ensuring the validity of data is triangulation. Data analysis techniques are data reduction, data presentation, and data verification. The results of the study can be concluded that SMA Negeri 12 Kerinci students have difficulty in understanding the concepts and learning materials and teachers has difficulty in practicing and evaluating learning outcomes, SMA Negeri 4 Kerinci students lack motivation and participation in learning and teachers have difficulty in making teaching materials, and MAS Koto Rendah students often experience internet network disruptions, students are less active in learning, and students have low motivation to learn virtually and teachers have difficulty in making teaching materials and explaining materials.

Phase-locking of resting-state brain networks with the gastric basal electrical rhythm

A network of myenteric interstitial cells of Cajal in the corpus of the stomach serves as its “pacemaker”, continuously generating a ca 0.05 Hz electrical slow wave, which is transmitted to the brain chiefly by vagal afferents. A recent study combining resting-state functional MRI (rsfMRI) with concurrent surface electrogastrography (EGG), with cutaneous electrodes placed on the epigastrium, found 12 brain regions with activity that was significantly phase-locked with this gastric basal electrical rhythm. Therefore, we asked whether fluctuations in brain resting state networks (RSNs), estimated using a spatial independent component analysis (ICA) approach, might be synchronized with the stomach. In the present study, in order to determine whether any RSNs are phase-locked with the gastric rhythm, an individual participant underwent 22 scanning sessions; in each, two 15-minute runs of concurrent EGG and rsfMRI data were acquired. EGG data from three sessions had weak gastric signals and were excluded; the other 19 sessions yielded a total of 9.5 hours of data. The rsfMRI data were analyzed using group ICA; RSN time courses were estimated; for each run, the phase-locking value (PLV) was computed between each RSN and the gastric signal. To assess statistical significance, PLVs from all pairs of “mismatched” data (EGG and rsfMRI data acquired on different days) were used as surrogate data to generate a null distribution for each RSN. Of a total of 18 RSNs, three were found to be significantly phase-locked with the basal gastric rhythm, namely, a cerebellar network, a dorsal somatosensory-motor network, and a default mode network. Disruptions to the gut-brain axis, which sustains interoceptive feedback between the central nervous system and the viscera, are thought to be involved in various disorders; manifestation of the infra-slow rhythm of the stomach in brain rsfMRI data could be useful for studies in clinical populations.