Risk Factors for Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Currently there is no effective treatment available. Senile plaques and neurofibrillary tangles are hallmarks of AD pathology, and patients demonstrate cognitive complaints with deficits in various neuropsychological domains. Familial AD (FAD) accounts for 0.5% of all AD cases and usually presents before the age of 65 years. Approximately 50% of the FAD patients carry mutations in one of the following genes: APP, PSEN1, and PSEN2. Inheriting any of these genetic mutations increases Aβ42 production, which has been linked to AD pathogenesis. Late-onset AD represents the majority of AD cases, with evidence suggesting impaired Aβ clearance. However, the etiology of late-onset AD is more complex. Several findings suggest that multiple risk genes and factors may contribute to the pathogenesis of LOAD. In this chapter, we elaborate some of these factors and their involvements in the development of AD

Robustness of maintenance support service networks : attributes, evaluation and improvement

Maintenance support service network (MSSN) is used to provide maintenance services and maintain the operational status of equipment. However, the performance of MSSN has been significantly influenced by inevitable disturbance, which makes it vital to maintain its robustness. Existing research on robustness of MSSN mainly focuses on single-layer rather than two-layer network, which imposes constraints on the disturbances and limits its application. To solve these issues, this study develops a two-layer MSSN, consisting of a directed entity-layer and an undirected cyber-layer focusing on supporting maintenance service. A definition of robustness for two-layer MSSN is proposed, and effect propagation models are established to evaluate its robustness of MSSN, followed by its improvement strategies. In particular, two strategies applied in the single-layer MSSN are modified to adapt to the two-layer MSSN, and a novel greedy partnership building approach is proposed to find an optimal strategy under cascading failure, to maintain the robustness of MSSN from a complex network perspective. Finally, numerical examples are presented to illustrate the effectiveness of the proposed approach

Molecular differences in brain regional vulnerability to aging between males and females

BackgroundAging-related cognitive decline is associated with brain structural changes and synaptic loss. However, the molecular mechanisms of cognitive decline during normal aging remain elusive.ResultsUsing the GTEx transcriptomic data from 13 brain regions, we identified aging-associated molecular alterations and cell-type compositions in males and females. We further constructed gene co-expression networks and identified aging-associated modules and key regulators shared by both sexes or specific to males or females. A few brain regions such as the hippocampus and the hypothalamus show specific vulnerability in males, while the cerebellar hemisphere and the anterior cingulate cortex regions manifest greater vulnerability in females than in males. Immune response genes are positively correlated with age, whereas those involved in neurogenesis are negatively correlated with age. Aging-associated genes identified in the hippocampus and the frontal cortex are significantly enriched for gene signatures implicated in Alzheimer’s disease (AD) pathogenesis. In the hippocampus, a male-specific co-expression module is driven by key synaptic signaling regulators including VSNL1, INA, CHN1 and KCNH1; while in the cortex, a female-specific module is associated with neuron projection morphogenesis, which is driven by key regulators including SRPK2, REPS2 and FXYD1. In the cerebellar hemisphere, a myelination-associated module shared by males and females is driven by key regulators such as MOG, ENPP2, MYRF, ANLN, MAG and PLP1, which have been implicated in the development of AD and other neurodegenerative diseases.ConclusionsThis integrative network biology study systematically identifies molecular signatures and networks underlying brain regional vulnerability to aging in males and females. The findings pave the way for understanding the molecular mechanisms of gender differences in developing neurodegenerative diseases such as AD

Altered gut microbiota in temporal lobe epilepsy with anxiety disorders

IntroductionPatients with epilepsy are particularly vulnerable to the negative effects of anxiety disorders. In particular, temporal lobe epilepsy with anxiety disorders (TLEA) has attracted more attention in epilepsy research. The link between intestinal dysbiosis and TLEA has not been established yet. To gain deeper insight into the link between gut microbiota dysbiosis and factors affecting TLEA, the composition of the gut microbiome, including bacteria and fungi, has been examined.MethodsThe gut microbiota from 51 temporal lobe epilepsy patients has been subjected to sequencing targeting 16S rDNA (Illumina MiSeq) and from 45 temporal lobe epilepsy patients targeting the ITS-1 region (through pyrosequencing). A differential analysis has been conducted on the gut microbiota from the phylum to the genus level.ResultsTLEA patients' gut bacteria and fungal microbiota exhibited distinct characteristics and diversity as evidenced by high-throughput sequencing (HTS). TLEA patients showed higher abundances of Escherichia-Shigella (genus), Enterobacterales (order), Enterobacteriaceae (family), Proteobacteria (phylum), Gammaproteobacteria (class), and lower abundances of Clostridia (class), Firmicutes, Lachnospiraceae (family), Lachnospirales (order), and Ruminococcus (genus). Among fungi, Saccharomycetales fam. incertae sedis (family), Saccharomycetales (order), Saccharomycetes (class), and Ascomycota (phylum) were significantly more abundant in TLEA patients than in patients with temporal lobe epilepsy but without anxiety. Adoption and perception of seizure control significantly affected TLEA bacterial community structure, while yearly hospitalization frequency affected fungal community structures in TLEA patients.ConclusionHere, our study validated the gut microbiota dysbiosis of TLEA. Moreover, the pioneering study of bacterial and fungal microbiota profiles will help in understanding the course of TLEA and drive us toward preventing TLEA gut microbiota dysbiosis

Lesional Intractable Epileptic Spasms in Children: Electroclinical Localization and Postoperative Outcomes

To analyze the influence of seizure semiology, electroencephalography (EEG) features and magnetic resonance imaging (MRI) change on epileptogenic zone localization and surgical prognosis in children with epileptic spasm (ES) were assessed. Data from 127 patients with medically intractable epilepsy with ES who underwent surgical treatment were retrospectively analyzed. ES semiology was classified as non-lateralized, bilateral asymmetric, and focal. Interictal epileptiform discharges were divided into diffusive or multifocal, unilateral, and focal. MRI results showed visible local lesions for all patients, while the anatomo-electrical-clinical value of localization of the epileptogenic zone was dependent on the surgical outcome. During preoperative video EEG monitoring, among all 127 cases, 53 cases (41.7%) had ES only, 46 (36.2%) had ES and focal seizures, 17 (13.4%) had ES and generalized seizures, and 11 (8.7%) had ES with focal and generalized seizures. Notably, 35 (27.6%) and 92 cases (72.4%) showed simple and complex ES, respectively. Interictal EEG showed that 22 cases (17.3%) had bilateral multifocal discharges or hypsarrhythmia, 25 (19.7%) had unilateral dominant discharges, and 80 (63.0%) had definite focal or regional discharges. Ictal discharges were generalized/bilateral in 71 cases (55.9%) and definite/lateralized in 56 cases (44.1%). Surgically resected lesions were in the hemisphere (28.3%), frontal lobe (24.4%), temporal lobe (16.5%), temporo-parieto-occipital region (14.2%), and posterior cortex region (8.7%). Seizure-free rates at 1 and 4 years postoperatively were 81.8 and 72.7%, respectively. There was no significant difference between electroclinical characteristics of ES and seizure-free rate. Surgical treatment showed good outcomes in most patients in this cohort. Semiology and ictal EEG change of ES had no effect on localization, while focal or lateralized epileptiform discharges of interictal EEG may affect lateralization and localization. Complete resection of epileptogenic lesions identified via MRI was the only factor associated with a positive surgical outcome

Resampling approach for anomaly detection in multispectral images

We propose a novel approach for identifying the “most unusual” samples in a data set, based on a resampling of data attributes. The resampling produces a “background class” and then binary classification is used to distinguish the original training set from the background. Those in the training set that are most like the background (i.e., most unlike the rest of the training set) are considered anomalous. Although by their nature, anomalies do not permit a positive definition (if I knew what they were, I wouldn’t call them anomalies), one can make “negative definitions” (I can say what does not qualify as an interesting anomaly). By choosing different resampling schemes, one can identify different kinds of anomalies. For multispectral images, anomalous pixels correspond to locations on the ground with unusual spectral signatures or, depending on how feature sets are constructed, unusual spatial textures

The characteristics of the complete chloroplast genome of Staurogyne concinnula (Hance) O. Kuntze (Acanthaceae)

Staurogyne concinnula (Hance) O. Kuntze (Acanthaceae) is an important ornamental herb mainly distributed in the southern region of China, including Fujian, Guangdong, Hainan, and Taiwan provinces. However, the complete chloroplast genome of S. concinnula, which could serve as a genetic resource for studies on its taxonomy and evolution, is poorly studied at present. In this study, we reported the complete chloroplast genome of S. concinnula that was assembled using high-throughput sequencing data. The chloroplast genome was 153,783 bp long, with a typical quadripartite structure containing a small single-copy region (SSC; 17,855 bp), a large single-copy region (LSC; 84,636 bp) and a pair of inverted repeats (IRs; each 25,646 bp). The overall GC content of the chloroplast genome was 38.04%. A total of 86 protein-coding genes (PCGs), 8 rRNA genes, and 37 tRNA genes were predicted. Phylogenetic analysis based on the combined sequences of 86 PCGs with the other 16 closely related species of Acanthaceae indicated that S. concinnula is closely related to Avicennia marina. The genomic data and finding from the phylogenetic studies of S. concinnula could provide useful information and give light to in-depth studies on the evolution pattern of the understudied species, as well as Staurogyne

Advances in developing novel therapeutic strategies for Alzheimer’s disease

Abstract Alzheimer’s Disease (AD), the most prevalent neurodegenerative disease of aging, affects one in eight older Americans. Nearly all drug treatments tested for AD today have failed to show any efficacy. There is a great need for therapies to prevent and/or slow the progression of AD. The major challenge in AD drug development is lack of clarity about the mechanisms underlying AD pathogenesis and pathophysiology. Several studies support the notion that AD is a multifactorial disease. While there is abundant evidence that amyloid plays a role in AD pathogenesis, other mechanisms have been implicated in AD such as tangle formation and spread, dysregulated protein degradation pathways, neuroinflammation, and loss of support by neurotrophic factors. Therefore, current paradigms of AD drug design have been shifted from single target approach (primarily amyloid-centric) to developing drugs targeted at multiple disease aspects, and from treating AD at later stages of disease progression to focusing on preventive strategies at early stages of disease development. Here, we summarize current strategies and new trends of AD drug development, including pre-clinical and clinical trials that target different aspects of disease (mechanism-based versus non-mechanism based, e.g. symptomatic treatments, lifestyle modifications and risk factor management)

Passivity-Based Adaptive Hybrid Synchronization of a New Hyperchaotic System with Uncertain Parameters

We investigate the adaptive hybrid synchronization problem for a new hyperchaotic system with uncertain parameters. Based on the passivity theory and the adaptive control theory, corresponding controllers and parameter estimation update laws are proposed to achieve hybrid synchronization between two identical uncertain hyperchaotic systems with different initial values, respectively. Numerical simulation indicates that the presented methods work effectively