Dissecting Alzheimer's disease pathogenesis in human 2D and 3D models.

The incidence of Alzheimer's disease is increasing with the aging population, and it has become one of the main health concerns of modern society. The dissection of the underlying pathogenic mechanisms and the development of effective therapies remain extremely challenging, also because available animal and cell culture models do not fully recapitulate the whole spectrum of pathological changes. The advent of human pluripotent stem cells and cell reprogramming has provided new prospects for tackling these challenges in a human and even patient-specific setting.

Cross-sectional study of the association between cataract surgery and age-related macular degeneration in the era of phacoemulsification in the national health and nutrition examination survey 2005-2008.

Objective: To determine the association between cataract surgery and age-related macular degeneration (AMD) in a representative US sample.

Design: Population-based, cross-sectional study.

Setting: The US National Health and Nutrition Examination Survey 2005-2008.

Control of Innate Immunity by Sialic Acids in the Nervous Tissue.

Sialic acids (Sias) are the most abundant terminal sugar residues of glycoproteins and glycolipids on the surface of mammalian cells. The nervous tissue is the organ with the highest expression level of Sias. The 'sialylation' of glycoconjugates is performed via sialyltransferases, whereas 'desialylation' is done by sialidases or is a possible consequence of oxidative damage.

Mechanistic Insights of Astrocyte-Mediated Hyperactive Autophagy and Loss of Motor Neuron Function in SOD1 Linked Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no cure. The reports showed the role of nearby astrocytes around the motor neurons as one among the causes of the disease. However, the exact mechanistic insights are not explored so far.

The Impact of Mitochondrial Dysfunction on Dopaminergic Neurons in the Olfactory Bulb and Odor Detection.

Understanding non-motor symptoms of Parkinson's disease is important in order to unravel the underlying molecular mechanisms of the disease. Olfactory dysfunction is an early stage, non-motor symptom which occurs in 95% of Parkinson's disease patients. Mitochondrial dysfunction is a key feature in Parkinson's disease and importantly contributes to the selective loss of dopaminergic neurons the substantia nigra pars compacta.

Transcription Factor-Based Fate Specification and Forward Programming for Neural Regeneration.

Traditionally, generation of donor cells for brain repair has been dominated by the application of extrinsic growth factors and morphogens. Recent advances in cell engineering strategies such as reprogramming of somatic cells into induced pluripotent stem cells and direct cell fate conversion have impressively demonstrated the feasibility to manipulate cell identities by the overexpression of cell fate-determining transcription factors. These strategies are now increasingly implemented for transcription factor-guided differentiation of neural precursors and forward programming of pluripotent stem cells toward specific neural subtypes.

The Association between Retinopathy and Arthritis: Findings from a US National Survey 2005-2008.

To explore the association between retinopathy and arthritis in a representative sample in the United States. National Health and Nutrition Examination Survey (NHANES) is a series of biannual surveys in a nationally representative non-institutionalized population of the United States. Two waves of NHANES (2005-2008) were merged in the current analysis.

A novel serum-free medium for the isolation, expansion and maintenance of stemness and tissue-specific markers of primary human periodontal ligament cells.

Purpose: Periodontal ligament (PDL) cell cultures are classically maintained in serum-containing media. However, unwanted side-effects of these conditions on cellular and molecular characteristics demand a serum-free alternative. Even though these limitations are well known and efforts for the development of adequate serum-free alternatives have been made, these approaches for replacement remained unsuccessful so far.

Reduced sialylation triggers homeostatic synapse and neuronal loss in middle-aged mice.

Sialic acid-binding Ig-like lectin (Siglec) receptors are linked to neurodegenerative processes, but the role of sialic acids in physiological aging is still not fully understood. We investigated the impact of reduced sialylation in the brain of mice heterozygous for the enzyme glucosamine-2-epimerase/N-acetylmannosamine kinase (GNE+/-) that is essential for sialic acid biosynthesis. We demonstrate that GNE+/- mice have hyposialylation in different brain regions, less synapses in the hippocampus and reduced microglial arborization already at 6 months followed by increased loss of neurons at 12 months.

Visual Impairment and Major Eye Diseases in Chronic Kidney Disease: The National Health and Nutrition Examination Survey, 2005-2008.

Purpose: To investigate the prevalence and associations of visual impairment (VI) and major eye diseases with chronic kidney disease (CKD) in the United States.

Design: Cross-sectional study.

Methods: We investigated the prevalence and associations of VI and major eye diseases with CKD among 5,518 participants aged 40 years or older in the 2005-2008 National Health and Nutrition Examination Survey.

Association between age-related macular degeneration and subjective cognitive complaints.

Purpose: To investigate the association between age-related macular degeneration (AMD) and subjective cognitive complaints (SCCs) in the USA.

Methods: A total of 5604 participants aged 40 years and older from the 2005-2008 National Health and Nutrition Examination Survey were included. Retinal photography was graded into no AMD, early and late AMD based on the modification of the Wisconsin Age-Related Maculopathy Grading System.

Impact of cognitive impairment and systemic vascular comorbidities on risk of all-cause and cardiovascular mortality: National Health and Nutrition Examination Survey 1999 to 2002.

Objectives: To evaluate impacts of cognitive impairment and systemic vascular comorbidities on hazards of all-cause and cardiovascular mortality in a representative United States population.

Methods: Subjects aged ≥60 years from two waves of National Health and Nutrition Examination Survey were analyzed. Cognitive function was evaluated by Digit Symbol Substitution Test.

Analysis of short tandem repeat expansions and their methylation state with nanopore sequencing.

Expansions of short tandem repeats are genetic variants that have been implicated in several neuropsychiatric and other disorders, but their assessment remains challenging with current polymerase-based methods. Here we introduce a CRISPR-Cas-based enrichment strategy for nanopore sequencing combined with an algorithm for raw signal analysis. Our method, termed STRique for short tandem repeat identification, quantification and evaluation, integrates conventional sequence mapping of nanopore reads with raw signal alignment for the localization of repeat boundaries and a hidden Markov model-based repeat counting mechanism.

Publisher Correction: Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Regulation of the autophagy-marker Sequestosome 1 in periodontal cells and tissues by biomechanical loading.

Purpose: Orthodontic treatment is based on the principle of force application to teeth and subsequently to the surrounding tissues and periodontal cells. Sequestosome 1 (SQSTM1) is a well-known marker for autophagy, which is an important cellular mechanism of adaptation to stress. The aim of this study was to analyze whether biomechanical loading conditions regulate SQSTM1 in periodontal cells and tissues, thereby providing further information on the role of autophagy in orthodontic tooth movement.

Evolving principles underlying neural lineage conversion and their relevance for biomedical translation.

Scientific and technological advances of the past decade have shed light on the mechanisms underlying cell fate acquisition, including its transcriptional and epigenetic regulation during embryonic development. This knowledge has enabled us to purposefully engineer cell fates by manipulating expression levels of lineage-instructing transcription factors. Here, we review the state of the art in the cell programming field with a focus on the derivation of neural cells.

Autophagy in periodontal ligament fibroblasts under biomechanical loading.

Autophagy (cellular self-consumption) is an adaptive stress response and an important aspect of adaption to mechanical loading. If mechanical forces are associated with autophagy regulation in periodontal ligament (PDL) fibroblasts is still unknown. The aim of this study was to analyze the influence of force magnitude on autophagy regulation and subsequently on cell death in human PDL fibroblasts.

In Vitro Recapitulation of Developmental Transitions in Human Neural Stem Cells.

During nervous system development, early neuroepithelial stem (NES) cells with a highly polarized morphology and responsiveness to regionalizing morphogens give rise to radial glia (RG) cells, which generate region-specific neurons. Recently, stable neural cell populations reminiscent of NES cells have been obtained from pluripotent stem cells and the fetal human hindbrain. Here, we explore whether these cell populations, similar to their in vivo counterparts, can give rise to neural stem (NS) cells with RG-like properties and whether region-specific NS cells can be generated from NES cells with different regional identities.

Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons.

Axonal degeneration is a key pathology of neurodegenerative diseases, including hereditary spastic paraplegia (HSP), a disorder characterized by spasticity in the lower limbs. Treatments for HSP and other neurodegenerative diseases are mainly symptomatic. While iPSC-derived neurons are valuable for drug discovery and target identification, these applications require robust differentiation paradigms and rapid phenotypic read-outs ranging between hours and a few days.

Altered Levels of Proteins and Phosphoproteins, in the Absence of Early Causative Transcriptional Changes, Shape the Molecular Pathogenesis in the Brain of Young Presymptomatic Ki91 SCA3/MJD Mouse.

Spinocerebellar ataxia type 3 (SCA3/MJD) is a polyQ neurodegenerative disease where the presymptomatic phase of pathogenesis is unknown. Therefore, we investigated the molecular network of transcriptomic and proteomic triggers in young presymptomatic SCA3/MJD brain from Ki91 knock-in mouse. We found that transcriptional dysregulations resulting from mutant ataxin-3 are not occurring in young Ki91 mice, while old Ki91 mice and also postmitotic patient SCA3 neurons demonstrate the late transcriptomic changes.

An Autaptic Culture System for Standardized Analyses of iPSC-Derived Human Neurons.

iPSC-derived human neurons are expected to revolutionize studies on brain diseases, but their functional heterogeneity still poses a problem. Key sources of heterogeneity are the different cell culture systems used. We show that an optimized autaptic culture system, with single neurons on astrocyte feeder islands, is well suited to culture, and we analyze human iPSC-derived neurons in a standardized, systematic, and reproducible manner.

A Single-Cell Model for Synaptic Transmission and Plasticity in Human iPSC-Derived Neurons.

Synaptic dysfunction is associated with many brain disorders, but robust human cell models to study synaptic transmission and plasticity are lacking. Instead, current in vitro studies on human neurons typically rely on spontaneous synaptic events as a proxy for synapse function. Here, we describe a standardized in vitro approach using human neurons cultured individually on glia microdot arrays that allow single-cell analysis of synapse formation and function.

Charged aerosol detector HPLC as a characterization and quantification application of biopharmaceutically relevant polysialic acid from E. coli K1.

Polysialic acid (polySia) is widely investigated in various biopharmaceutical applications (e.g. treatment of inflammatory neurodegenerative diseases), whereby a certain polySia chain length with an average degree of polymerization 20 (polySia avDP20) shows most promising effects.