Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model.

(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. (2) Methods: Here, we report the histological effects of long-term treatment with an SPM, maresin-like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model.

Upregulating ANKHD1 in PS19 mice reduces Tau phosphorylation and mitigates Tau-toxicity-induced cognitive deficits.

Abnormal accumulation of Tau protein in the brain disrupts normal cellular function and leads to neuronal death linked with many neurodegenerative disorders such as Alzheimer's disease. An attractive approach to mitigate Tau-induced neurodegeneration is to enhance the clearance of toxic Tau aggregates. We previously showed that upregulation of the fly gene protects against FUS- and Tau-induced photoreceptor degeneration in fly disease models.

dwMLCS: An Efficient MLCS Algorithm based on Dynamic and Weighted Directed Acyclic Graph.

The problem of finding the longest common subsequence (MLCS) for multiple sequences is a computationally intensive and challenging problem that has significant applications in various fields such as text comparison, pattern recognition, and gene diagnosis. Currently, the dominant point-based MLCS algorithms have become popular and extensively studied. Generally, they construct the directed acyclic graph (DAG) of matching points and convert the MLCS problem into a search for the longest paths in the DAG.

A novel open-source CADs platform for 3D CT pulmonary analysis.

Computer-aided diagnosis (CAD) systems play vital roles in the early detection of pulmonary nodules for reducing lung cancer mortality rates. To provide better services for professional doctors, this paper proposes an efficient open-source CAD platform with flexible equipments, user-friendly interfaces, and completed functions for 3D CT pulmonary nodule analysis. For the platform's design and implementation, we fully consider application scenarios and system requirements.

Distributed multi-objective optimization for SNP-SNP interaction detection.

The detection of complex interactions between single nucleotide polymorphisms (SNPs) plays a vital role in genome-wide association analysis (GWAS). The multi-objective evolutionary algorithm is a promising technique for SNP-SNP interaction detection. However, as the scale of SNP data further increases, the exponentially growing search space gradually becomes the dominant factor, causing evolutionary algorithm (EA)-based approaches to fall into local optima.

MiniDBG: A Novel and Minimal De Bruijn Graph for Read Mapping.

The De Bruijn graph (DBG) has been widely used in the algorithms for indexing or organizing read and reference sequences in bioinformatics. However, a DBG model that can locate each node, edge and path on sequence has not been proposed so far. Recently, DBG has been used for representing reference sequences in read mapping tasks.

Automatic Code Review by Learning the Structure Information of Code Graph.

At present, the explosive growth of software code volume and quantity makes the code review process very labor-intensive and time-consuming. An automated code review model can assist in improving the efficiency of the process. Tufano et al.

I/O Efficient Early Bursting Cohesive Subgraph Discovery in Massive Temporal Networks.

Unlabelled: Temporal networks are an effective way to encode temporal information into graph data losslessly. Finding the bursting cohesive subgraph (BCS), which accumulates its cohesiveness at the fastest rate, is an important problem in temporal networks. The BCS has a large number of applications, such as representing emergency events in social media, traffic congestion in road networks and epidemic outbreak in communities.

An AI-Driven Hybrid Framework for Intrusion Detection in IoT-Enabled E-Health.

E-health has grown into a billion-dollar industry in the last decade. Its device's high throughput makes it an obvious target for cyberattacks, and these environments desperately need protection. In this scientific study, we presented an artificial intelligence (AI)-driven software-defined networking (SDN)-enabled intrusion detection system (IDS) to address increasing cyber threats in the E-health and internet of medical things (IoMT) environments.

Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease.

The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum's small ionic size and highly electrophilic nature, having the highest charge density of any metallic cation with a Z/r of 18 (ionic charge +3, radius 0.5 nm); inclination to form extremely stable electrostatic bonds with a tendency towards covalency; ability to interact irreversibly and/or significantly slow down the exchange-rates of complex aluminum-biomolecular interactions; extremely dense electropositive charge with one of the highest known affinities for oxygen-donor ligands such as phosphate; presence as the most abundant metal in the Earth's biosphere and general bioavailability in drinking water, food, medicines, consumer products, groundwater and atmospheric dust; and abundance as one of the most commonly encountered intracellular and extracellular metallotoxins.

Downregulation of Neurofilament Light Chain Expression in Human Neuronal-Glial Cell Co-Cultures by a Microbiome-Derived Lipopolysaccharide-Induced miRNA-30b-5p.

Microbiome-derived Gram-negative bacterial lipopolysaccharide (LPS) has been shown by multiple laboratories to reside within Alzheimer's disease (AD)-affected neocortical and hippocampal neurons. LPS and other pro-inflammatory stressors strongly induce a defined set of NF-kB (p50/p65)-sensitive human microRNAs, including a brain-enriched microRNA-30b-5p (hsa-miRNA-30b-5p; miRNA-30b). Here we provide evidence that this neuropathology-associated miRNA, known to be upregulated in AD brain and LPS-stressed human neuronal-glial (HNG) cells in primary culture targets the neurofilament light (NF-L) chain mRNA 3'-untranslated region (3'-UTR), which is conducive to the post-transcriptional downregulation of NF-L expression observed within both AD and LPS-treated HNG cells.

microRNA-146a as a biomarker for transmissible spongiform encephalopathy.

The pro-inflammatory, innate-immune system ribonucleic acid mediator microRNA-146a, constitutively expressed in the brain and central nervous system (CNS) of both the mouse and the human, is pathologically up-regulated in multiple transmissible spongiform encephalopathies (TSEs) to several times its basal level. miRNA-146a: (i) exists as a ~22-ribonucleotide (nt) single-stranded non-coding RNA (sncRNA) whose sequence is unique and highly selected over evolution; (ii) is brain-, CNS- and lymphoid-tissue enriched and exhibits a 100% RNA sequence homology between the mouse and the human; (iii) has been repeatedly shown to play critical immunological and pro-inflammatory roles in the onset and propagation of several human CNS disorders including progressive, incapacitating, and lethal neurological syndromes that include prion disease (PrD) and Alzheimer's disease (AD); (iv) is a fascinating molecular entity because it is representative of the smallest class of soluble, information-carrying, amphipathic sncRNA yet described; (v) has capability to be induced by cellular stressors and the pro-inflammatory transcription factor NF-kB (p50/p65); (vi) has capability to post-transcriptionally regulate multiple mRNAs and cellular processes in neurological health and disease; (vii) is upregulated in human host cells after viral invasion by single-stranded RNA (ssRNA) or double-stranded DNA (dsDNA) neurotropic viruses; and (viii) has an immense potential in neuro-degenerative disease therapeutics via anti-NF-kB and/or anti-miRNA-146a treatment strategies. In this short communication we provide for the first time evidence that miRNA-146a is a prominent sncRNA species in experimental murine prion disease, progressively increasing in the pre-symptomatic stages in C57BL/6J, SJL/J or Swiss Albino murine scrapie prion models.

Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery.

Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such as synapsin-2 (SYN II) degrade rapidly via the ubiquitin-proteasome pathway, a considerably more stable neurofilament light (NF-L) chain protein turns over much more slowly, and in several neurological diseases is accompanied by a pathological shift from an intracellular neuronal cytoplasmic location into various biofluid compartments. NF-L has been found to be significantly elevated in peripheral biofluids in multiple neurodegenerative disorders, however it is not as widely appreciated that NF-L expression within neurons undergoing inflammatory neurodegeneration exhibit a significant down-regulation in these neuron-specific intermediate-filament components.

DiagAF: A More Accurate and Efficient Pre-Alignment Filter for Sequence Alignment.

Sequence alignment is an essential step in computational genomics. More accurate and efficient sequence pre-alignment methods that run before conducting expensive computation for final verification are still urgently needed. In this article, we propose a more accurate and efficient pre-alignment algorithm for sequence alignment, called DiagAF.

Gastrointestinal Tract Microbiome-Derived Pro-inflammatory Neurotoxins in Alzheimer's Disease.

The microbiome contained within the human gastrointestinal (GI)-tract constitutes a highly complex, dynamic and interactive internal prokaryotic ecosystem that possesses a staggering diversity, speciation and complexity. This repository of microbes comprises the largest interactive source and highest density of microbes anywhere in nature, collectively constituting the largest 'diffuse organ system' in the human body. Through the extracellular fluid (ECF), cerebrospinal fluid (CSF), lymphatic and glymphatic circulation, endocrine, systemic and neurovascular circulation and/or central and peripheral nervous systems (CNS, PNS) microbiome-derived signaling strongly impacts the health, well-being and vitality of the human host.

Ubiquity of the SARS-CoV-2 receptor ACE2 and upregulation in limbic regions of Alzheimer's disease brain.

The major route of entry for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into human host cells is by means of the angiotensin-converting enzyme-2 (ACE2) transmembrane receptor. This zinc-containing carboxypeptidase and membrane-integral surface receptor is ubiquitous and widely expressed in multiple cell types. Hence SARS-CoV-2, an unusually large RNA virus that causes coronavirus disease 2019 (COVID-19) has the remarkable capacity to invade many different types of human host cells simultaneously.

Gastrointestinal (GI)-Tract Microbiome Derived Neurotoxins and their Potential Contribution to Inflammatory Neurodegeneration in Alzheimer's Disease (AD).

The human gastrointestinal (GI)-tract microbiome is a rich, complex and dynamic source of microorganisms that possess a staggering diversity and complexity. Importantly there is a significant variability in microbial complexity even amongst healthy individuals-this has made it difficult to link specific microbial abundance patterns with age-related neurological disease. GI-tract commensal microorganisms are generally beneficial to human metabolism and immunity, however enterotoxigenic forms of microbes possess significant potential to secrete what are amongst the most neurotoxic and pro-inflammatory biopolymers known.

An Efficient Method for Modeling Nonoccurring Behaviors by Negative Sequential Patterns With Loose Constraints.

The sequence analysis handles sequential discrete events and behaviors, which can be represented by temporal point processes (TPPs). However, TPP models only occurring events and behaviors. This article explores an efficient method for the negative sequential pattern (NSP) mining to leverage TPP in modeling both frequently occurring and nonoccurring events and behaviors.

StLiter: A Novel Algorithm to Iteratively Build the Compacted de Bruijn Graph From Many Complete Genomes.

Recently, the compacted de Bruijn graph (cDBG) of complete genome sequences was successfully used in read mapping due to its ability to deal with the repetitions in genomes. However, current approaches are not flexible enough to fit frequently building the graphs with different k-mer lengths. Instead of building the graph directly, how can we build the compacted de Bruijin graph of longer k-mer based on the one of short k-mer? In this article, we present StLiter, a novel algorithm to build the compacted de Bruijn graph either directly from genome sequences or indirectly based on the graph of a short k-mer.

MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints.

There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer's disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increased risk of AD.