Post-transcriptional modifications on tRNA fragments confer functional changes to high-density lipoproteins in atherosclerosis.

Epitranscriptomic modifications on RNA play critical roles in stability, processing, and function, partly by influencing interactions with RNA-binding proteins and receptors. The role of post-transcriptional RNA modifications on cell-free non-coding small RNA (sRNA) remains poorly understood in disease contexts. High-density lipoproteins (HDL), which transport sRNAs, can lose their beneficial properties in atherosclerosis cardiovascular disease (ASCVD).

Transfer of and increases 3D growth and invasiveness in recipient cancer cells.

Aim: Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Cancer cells upregulate and secrete abundant levels of and that can alter gene expression in donor and recipient cells. In this study, we sought to identify targets of and and conclusively demonstrate that microRNAs (miRNAs) can be functionally transferred from donor to recipient cells.

5-Fluorouracil treatment represses pseudouridine-containing miRNA export into extracellular vesicles.

5-Fluorouracil (5-FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5-FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function.

The impact of aerobic endurance training on cognitive performance in schizophrenic inpatients in a clinical routine setting.

The primary aim of this study was to investigate the impact of aerobic endurance training in schizophrenic inpatients on cognitive performance in a clinical routine setting. Of secondary interest was the influence on psychopathological symptoms. A total of 31 schizophrenic inpatients were randomly assigned to receive either controlled endurance training or occupational therapy.

5-Fluorouracil Treatment Represses Pseudouridine-Containing Small RNA Export into Extracellular Vesicles.

5-fluorouracil (5-FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5-FU is also incorporated into RNA causing toxicity due to defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function.

Composition and Bioactivity of a Placental Tissue Particulate (PTP-001) Indicate Greater Potential than Platelet-Rich Plasma for the Treatment of Osteoarthritis.

Objective: This study was conducted to compare therapeutically relevant properties of platelet-rich plasma (PRP), a commonly used autologous intra-articular treatment for osteoarthritis (OA), with those of a novel placental tissue particulate, PTP-001, which is in development as a regulated biologic treatment for knee OA.

Design: Quantitative immunoassays were performed to determine the content of key growth/regulatory biofactors in PTP-001, and in leukocyte-rich (LR)-PRP or leukocyte-poor (LP)-PRP. An anti-inflammatory bioassay was used to evaluate the effects of each treatment on pro-inflammatory cytokine (tumor necrosis factor (TNF)-α) production in a macrophage cell culture system.

LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8.

Macrophages present a spectrum of phenotypes that mediate both the pathogenesis and resolution of atherosclerotic lesions. Inflammatory macrophage phenotypes are pro-atherogenic, but the stimulatory factors that promote these phenotypes remain incompletely defined. Here we demonstrate that microbial small RNAs (msRNA) are enriched on low-density lipoprotein (LDL) and drive pro-inflammatory macrophage polarization and cytokine secretion via activation of the RNA sensor toll-like receptor 8 (TLR8).

Elucidation of physico-chemical principles of high-density lipoprotein-small RNA binding interactions.

Extracellular small RNAs (sRNAs) are abundant in many biofluids, but little is known about their mechanisms of transport and stability in RNase-rich environments. We previously reported that high-density lipoproteins (HDLs) in mice were enriched with multiple classes of sRNAs derived from the endogenous transcriptome, but also from exogenous organisms. Here, we show that human HDL transports tRNA-derived sRNAs (tDRs) from host and nonhost species, the profiles of which were found to be altered in human atherosclerosis.

Predicting disease progression in behavioral variant frontotemporal dementia.

Introduction: The behavioral variant of frontotemporal dementia (bvFTD) is a rare neurodegenerative disease. Reliable predictors of disease progression have not been sufficiently identified. We investigated multivariate magnetic resonance imaging (MRI) biomarker profiles for their predictive value of individual decline.

Utility of the Repeat and Point Test for Subtyping Patients With Primary Progressive Aphasia.

Background: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA).

Objective: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA.

Method: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture.

A novel placental tissue biologic, PTP-001, inhibits inflammatory and catabolic responses in vitro and prevents pain and cartilage degeneration in a rat model of osteoarthritis.

Objective: Characterization of a novel human placental tissue-derived biologic, PTP-001, which is in development as a candidate therapeutic for the treatment of osteoarthritis symptoms and pathophysiology.

Methods: Human placental tissues from healthy donors were prepared as a particulate formulation, PTP-001. PTP-001 extracts were assayed for the presence of disease-relevant biofactors which could have beneficial effects in treating osteoarthritis.

Quantifying progression in primary progressive aphasia with structural neuroimaging.

Introduction: The term primary progressive aphasia (PPA) sums up the non-fluent (nfv), the semantic (sv), and the logopenic (lv) variant. Up to now, there is only limited data available concerning magnetic resonance imaging volumetry to monitor disease progression.

Methods: Structural brain imaging and an extensive assessment were applied at baseline and up to 4-year(s) follow-up in 269 participants.

Comparing cellular bone matrices for posterolateral spinal fusion in a rat model.

Introduction: Cellular bone matrices (CBM) are allograft products that provide three components essential to new bone formation: an osteoconductive scaffold, extracellular growth factors for cell proliferation and differentiation, and viable cells with osteogenic potential. This is an emerging technology being applied to augment spinal fusion procedures as an alternative to autografts.

Methods: We aim to compare the ability of six commercially-available human CBMs (Trinity ELITE®, ViviGen®, Cellentra®, Osteocel® Pro, Bio4® and Map3®) to form a stable spinal fusion using an athymic rat model of posterolateral fusion.

A Comparative Evaluation of Commercially Available Cell-Based Allografts in a Rat Spinal Fusion Model.

Background: To evaluate the comparative abilities of commercially available, viable, cellular bone allografts to promote posterolateral spinal fusion.

Methods: Human allografts containing live cells were implanted in the athymic rat model of posterolateral spine fusion. Three commercially available allogeneic cellular bone matrices (Trinity Evolution, Trinity ELITE and Osteocel Plus) were compared with syngeneic iliac crest bone as the control.

Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis.

Serum starvation stimulates cilia growth in cultured cells, yet serum factors associated with ciliogenesis are unknown. Previously, we showed that starvation induces rapid Rab11-dependent vesicular trafficking of Rabin8, a Rab8 guanine-nucleotide exchange factor (GEF), to the mother centriole, leading to Rab8 activation and cilium growth. Here, we demonstrate that through the LPA receptor 1 (LPAR1), serum lysophosphatidic acid (LPA) inhibits Rab11a-Rabin8 interaction and ciliogenesis.

Publisher Correction: Investigation of F-BAR domain PACSIN proteins uncovers membrane tubulation function in cilia assembly and transport.

In the original version of this Article, the fifth sentence of the abstract incorrectly read 'Remarkably, we show that PACSIN1 and EHD1 assemble membrane t7ubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel (EMC) to the outside of the cell.', and should have read 'Remarkably, we show that PACSIN1 and EHD1 assemble membrane tubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel (EMC) to the outside of the cell.'.

Investigation of F-BAR domain PACSIN proteins uncovers membrane tubulation function in cilia assembly and transport.

The intracellular ciliogenesis pathway requires membrane trafficking, fusion, and reorganization. Here, we demonstrate in human cells and zebrafish that the F-BAR domain containing proteins PACSIN1 and -2 play an essential role in ciliogenesis, similar to their binding partner and membrane reorganizer EHD1. In mature cilia, PACSINs and EHDs are dynamically localized to the ciliary pocket membrane (CPM) and transported away from this structure on membrane tubules along with proteins that exit the cilium.

Moral judgment in patients with behavioral variant of frontotemporal dementia and amyotrophic lateral sclerosis: no impairment of the moral position, but rather its execution.

Objective: To investigate moral judgment competence in patients with the behavioral variant frontotemporal dementia (bvFTD) compared to amyotrophic lateral sclerosis (ALS) and controls.

Methods: N = 12 bvFTD, N = 22 ALS patients and N = 19 neurological unimpaired controls were examined. In the 'Moral Competence Test' (MCT), participants had to evaluate two moral dilemmas by predefined arguments to measure the consistency of their moral judgments.

Story of the ALS-FTD continuum retold: rather two distinct entities.

Objective: To determine the evolution and profile of cognitive and behavioural deficits in amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) to disentangle the development of FTD in ALS and vice versa.

Methods: In a prospective design, cognitive and behavioural profiles of 762 patients with motor predominant ALS (flail arm/leg syndrome, primary lateral sclerosis, pseudobulbar palsy, ALS) and behavioural predominant FTD (bvFTD, ALS-FTD) were determined and caregivers of patients with ALS were asked on the evolution of behavioural symptoms. Data were compared with 49 healthy controls.

Serum neurofilament light chain in behavioral variant frontotemporal dementia.

Objective: To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD).

Methods: Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry.

Results: At baseline, serum NfL level correlated with CSF NfL (bvFTD = 0.

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia.

Background: With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.

Atrophy in the Thalamus But Not Cerebellum Is Specific for FTD and ALS Patients - An Atlas-Based Volumetric MRI Study.

The neuropathology of patients with frontotemporal dementia (FTD) or amyotrophic lateral sclerosis (ALS) due to a mutation is characterized by two distinct types of characteristic protein depositions containing either TDP-43 or so-called dipeptide repeat proteins that extend beyond frontal and temporal regions. Thalamus and cerebellum seem to be preferentially affected by the dipeptide repeat pathology unique to mutation carriers. This study aimed to determine if mutation carriers showed an enhanced degree of thalamic and cerebellar atrophy compared to sporadic patients or healthy controls.

In Vitro Modeling Using Ciliopathy-Patient-Derived Cells Reveals Distinct Cilia Dysfunctions Caused by CEP290 Mutations.

Mutations in CEP290, a transition zone protein in primary cilia, cause diverse ciliopathies, including Leber congenital amaurosis (LCA) and Joubert-syndrome and related disorders (JSRD). We examined cilia biogenesis and function in cells derived from CEP290-LCA and CEP290-JSRD patients. CEP290 protein was reduced in LCA fibroblasts with no detectable impact on cilia; however, optic cups derived from induced pluripotent stem cells (iPSCs) of CEP290-LCA patients displayed less developed photoreceptor cilia.