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Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder.

Brain 2021 Apr 14. Epub 2021 Apr 14.

Department of Neurosciences, Biomedicine and Movement Sciences University of Verona, Verona, Italy.

Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson's disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies. Read More

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Ligament-Inspired Tough and Anisotropic Fibrous Gel Belt with Programed Shape Deformations Dynamic Stretching.

ACS Appl Mater Interfaces 2021 Apr 14. Epub 2021 Apr 14.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, 2999 North Renmin Road, Shanghai 201620, P. R. China.

Nature provides perpetual inspiration for exploring anisotropic materials to implement complex functions and motions like biological organisms. In particular, fibrous hydrogel-based anisotropic aggregates have attracted tremendous interest as fantastic materials for development into artificial ligaments or muscles. Such aggregates combine the structural anisotropy and macroscopic flexibility of fiber materials, with the intelligence, softness, and wetness of hydrogel materials. Read More

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A Comparative Analysis of Quantitative Metrics of Root Architecture.

Plant Phenomics 2021 24;2021:6953197. Epub 2021 Feb 24.

Department of Plant Science, The Pennsylvania State University, University Park, PA 16802, USA.

High throughput phenotyping is important to bridge the gap between genotype and phenotype. The methods used to describe the phenotype therefore should be robust to measurement errors, relatively stable over time, and most importantly, provide a reliable estimate of elementary phenotypic components. In this study, we use functional-structural modeling to evaluate quantitative phenotypic metrics used to describe root architecture to determine how they fit these criteria. Read More

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February 2021

Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components.

Neuron 2021 Apr 7. Epub 2021 Apr 7.

Department of Biochemistry, University of Colorado, Boulder, CO, USA; Howard Hughes Medical Institute, University of Colorado, Boulder, CO, USA. Electronic address:

Tau aggregates contribute to neurodegenerative diseases, including frontotemporal dementia and Alzheimer's disease (AD). Although RNA promotes tau aggregation in vitro, whether tau aggregates in cells contain RNA is unknown. We demonstrate, in cell culture and mouse brains, that cytosolic and nuclear tau aggregates contain RNA with enrichment for small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). Read More

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LGR6 marks nephron progenitor cells.

Dev Dyn 2021 Apr 13. Epub 2021 Apr 13.

Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.

Background: Nephron progenitor cells (NPCs) undergo a stepwise process to generate all mature nephron structures. Mesenchymal to epithelial transition (MET) is considered a multi-step process of NPC differentiation to ensure progressive establishment of new nephrons. However, despite this important role, to date, no marker for NPCs undergoing MET in the nephron exists. Read More

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The Use, Standardization, and Interpretation of Brain Imaging Data in Clinical Trials of Neurodegenerative Disorders.

Authors:
Adam J Schwarz

Neurotherapeutics 2021 Apr 12. Epub 2021 Apr 12.

Takeda Pharmaceuticals Ltd., 40 Landsdowne Street, Cambridge, MA, 02139, USA.

Imaging biomarkers play a wide-ranging role in clinical trials for neurological disorders. This includes selecting the appropriate trial participants, establishing target engagement and mechanism-related pharmacodynamic effect, monitoring safety, and providing evidence of disease modification. In the early stages of clinical drug development, evidence of target engagement and/or downstream pharmacodynamic effect-especially with a clear relationship to dose-can provide confidence that the therapeutic candidate should be advanced to larger and more expensive trials, and can inform the selection of the dose(s) to be further tested, i. Read More

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Corrosion and transformation of solution combustion synthesized Co, Ni and CoNi nanoparticles in synthetic freshwater with and without natural organic matter.

Sci Rep 2021 Apr 12;11(1):7860. Epub 2021 Apr 12.

Division of Surface and Corrosion Science, Department of Chemistry, KTH Royal Institute of Technology, Stockholm, Sweden.

Pure metallic Co, Ni, and their bimetallic compositions of CoNi, CoNi, and CoNi nanomaterials were prepared by solution combustion synthesis. Microstructure, phase composition, and crystalline structure of these nanoparticles (NPs) were characterized along with studies of their corrosion and dissolution properties in synthetic freshwater with and without natural organic matter (NOM). The nanomaterials consisted of aggregates of fine NPs (3-30 nm) of almost pure metallic and bimetallic crystal phases with a thin surface oxide covered by a thin carbon shell. Read More

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The lectin Orysata induces phosphatase-mediated and carbohydrate-independent aggregation of insect cells.

J Insect Physiol 2021 Apr 9:104241. Epub 2021 Apr 9.

Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.

Lectins, or carbohydrate-binding proteins, can cause agglutination of particular cells. This process is mediated by the interaction of the carbohydrate-binding domain with sugar structures on the cell surface, and this binding can be inhibited by pre-incubation of the lectin with its specific sugars. However, when incubated with insect cells, Orysata, a mannose-binding lectin from rice, caused aggregation of the cells, independent from carbohydrate binding activity. Read More

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Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies.

Front Aging Neurosci 2021 25;13:648982. Epub 2021 Mar 25.

Department of Neurology, National Hospital Organization, Sendai Nishitaga Hospital, Sendai, Japan.

Parkinson's disease (PD) and multiple system atrophy are types of adult-onset neurodegenerative disorders named synucleinopathies, which are characterized by prominent intracellular α-synuclein (αSyn) aggregates. We have previously found that αSyn aggregates and the vulnerability of dopaminergic neurons in the mouse brain are partly associated with the expression of fatty acid-binding protein 3 (FABP3, heart FABP). However, it remains to be elucidated whether FABP3 accumulation is associated with αSyn aggregates in human tissues. Read More

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Generation and characterization of a laforin nanobody inhibitor.

Clin Biochem 2021 Apr 5. Epub 2021 Apr 5.

Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, United States; Lafora Epilepsy Cure Initiative, University of Kentucky College of Medicine, Lexington, KY 40536, United States. Electronic address:

Objectives: Mutations in the gene encoding the glycogen phosphatase laforin result in the fatal childhood dementia Lafora disease (LD). A cellular hallmark of LD is cytoplasmic, hyper-phosphorylated, glycogen-like aggregates called Lafora bodies (LBs) that form in nearly all tissues and drive disease progression. Additional tools are needed to define the cellular function of laforin, understand the pathological role of laforin in LD, and determine the role of glycogen phosphate in glycogen metabolism. Read More

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Tau strains shape disease.

Acta Neuropathol 2021 Apr 8. Epub 2021 Apr 8.

Center for Alzheimer's and Neurodegenerative Diseases, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Tauopathies consist of over 25 different neurodegenerative diseases that include argyrophilic grain disease (AGD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease (PiD). Tauopathies are defined by brain accumulation of microtubule-associated protein tau in fibrillar aggregates, whose prevalence strongly correlates with dementia. Dominant mutations in tau cause neurodegenerative diseases, and most increase its aggregation propensity. Read More

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MICROSPORIDIA-ASSOCIATED GRANULOMATOUS DISEASE IN TWO AUSTRALIAN COLLECTIONS OF CAPTIVE INLAND BEARDED DRAGONS ().

J Zoo Wildl Med 2021 Apr;52(1):396-400

School of Veterinary Medicine, Murdoch University, Murdoch, Western Australia, 6150, Australia.

Microsporidia are obligate, intracellular fungi. In reptiles, they are most commonly reported in squamates. We report the first detection of microsporidiosis in inland bearded dragons () from Australia, and for the first time, mixed infections of microsporidium and adenovirus in asymptomatic inland bearded dragons. Read More

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Detection of Dermal Alpha-Synuclein Deposits as a Biomarker for Parkinson's Disease.

Authors:
Kathrin Doppler

J Parkinsons Dis 2021 Mar 27. Epub 2021 Mar 27.

University Hospital Würzburg, Department of Neurology, Würzburg, Germany.

Alpha-synuclein deposits are detectable in skin biopsies of patients with Parkinson's disease and other synucleinopathies like multiple system atrophy by immunohistochemical staining. As they are easily to obtain, they appear a promising tool for the pre-mortem histopathological confirmation of the disease and as a potential outcome measure in studies targeting alpha-synuclein aggregates. Good sensitivity, specificity, and practicability are the most important requirements of a biomarker. Read More

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Tau Protein Phosphorylated at Threonine-231 is Expressed Abundantly in the Cerebellum in Prion Encephalopathies.

J Alzheimers Dis 2021 Apr 2. Epub 2021 Apr 2.

National Dementia BioBank. Ciencias Biológicas, Facultad de Estudios Superiores, Cuautitlán, UNAM, Estado de México, México.

Background: Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called "prion", which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. Read More

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Cross-linking of carbonic anhydrase and formate dehydrogenase based on amino acid specific recognition: Conversion of carbon dioxide to formic acid.

Enzyme Microb Technol 2021 May 13;146:109763. Epub 2021 Feb 13.

National Energy R&D Center for Biorefinery, Beijing University of Chemical Technology, Beijing, 100029, PR China.

Inspired by the cascades performed in vivo, the assembly of multiple enzymes in vitro has strongly moved into the focus of researchers in the field of biocatalysis. In this study, a new, mild and accurate enzyme cross-linking method is revealed. Microbial transglutaminase (MTG) acts as a "cross-linking medium" by identifying the amide group of the glutamine and the primary amine group of lysine in the artificial peptide tags specifically to form an iso-peptide bond. Read More

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Mechanisms of Neurodegeneration in Various Forms of Parkinsonism-Similarities and Differences.

Cells 2021 Mar 16;10(3). Epub 2021 Mar 16.

Department of Neurology, Faculty of Heath Science, Medical University of Warsaw, 03-285 Warsaw, Poland.

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Read More

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Designing the Composition of Cement-Stabilized Rammed Earth with the Association Analysis Application.

Materials (Basel) 2021 Mar 12;14(6). Epub 2021 Mar 12.

Institute of Construction Engineering, Faculty of Civil Engineering, Warsaw University of Technology, 00-637 Warsaw, Poland.

The main advantage of the structural composite material known as cement-stabilized rammed earth (CSRE) is that it can be formulated as a sustainable and cost-saving solution. The use of the aggregates collected very close to a construction site allows economizing on transportation costs. Another factor that makes sustainability higher and the costs lower is a small addition of cement to the CSRE in comparison to the regular concrete. Read More

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Covalently bonded hopanoid-Lipid A from Bradyrhizobium: The role of unusual molecular structure and calcium ions in regulating the lipid bilayers organization.

J Colloid Interface Sci 2021 Mar 18;594:891-901. Epub 2021 Mar 18.

CSGI, Center for Colloid and Surface Science, via della Lastruccia 3, Sesto Fiorentino (FI), Italy; Department of Chemical Sciences, University of Naples Federico II, via Cintia 4, 80126 Naples, Italy. Electronic address:

Lipopolysaccharides (LPS) are complex amphiphilic macromolecules forming the external leaflet of the outer membrane of Gram-negative bacteria. The LPS glycolipid portion, named Lipid A, is characterized by a disaccharide backbone carrying multiple acyl chains. Some Lipid A bear very-long-chain-fatty-acids (VLCFA), biosynthesized to span the entire lipid membrane profile. Read More

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NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance.

Aging Cell 2021 Mar 31:e13348. Epub 2021 Mar 31.

Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.

NELF-mediated pausing of RNA polymerase II (RNAPII) constitutes a crucial step in transcription regulation. However, it remains unclear how control release of RNAPII pausing can affect the epigenome and regulate important aspects of animal physiology like aging. We found that NELF-A dosage regulates Drosophila healthspan: Halving NELF-A level in the heterozygous mutants or via neuronal-specific RNAi depletion improves their locomotor activity, stress resistance, and lifespan significantly. Read More

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A multiscale model for multiple platelet aggregation in shear flow.

Biomech Model Mechanobiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, 11794, USA.

We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low-intermediate shear viscous flow, in which aggregation is mediated by the interaction of αβ receptors on the platelet membrane and fibrinogen (Fg). This multiscale model uses coarse grained molecular dynamics (CGMD) for platelets at the microscales and dissipative particle dynamics (DPD) for the shear flow at the macroscales, employing our hybrid aggregation force field for modeling molecular level receptor ligand bonds. We define an aggregation tensor and use it to quantify the molecular level contact characteristics between platelets in an aggregate. Read More

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Repurposing a Cardiovascular Disease Drug of Cloridarol as hIAPP Inhibitor.

ACS Chem Neurosci 2021 Mar 29. Epub 2021 Mar 29.

Department of Chemical, Biomolecular, and Corrosion Engineering The University of Akron, Ohio 44325, United States.

Accumulating evidence have shown a strong pathological correlation between cardiovascular disease (CVD) and Type II diabetes (T2D), both of which share many common risk factors (e.g., hyperglycemia, hypertension, hypercoagulability, and dyslipidemia) and mutually contribute to each other. Read More

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Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets.

Front Immunol 2021 12;12:634386. Epub 2021 Mar 12.

Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.

Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. Read More

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Landfill mining in Europe: Assessing the economic potential of value creation from generated combustibles and fines residue.

Waste Manag 2021 Mar 25;126:221-230. Epub 2021 Mar 25.

Division of Environmental Technology and Management, Department of Management and Engineering, Linköping University, 58183 Linköping, Sweden.

Previous studies showed that resources recovery through landfill mining (LFM) is generally challenging from an economic perspective and that a large share of project costs is related to the external treatment and disposal of bulk process wastes such as combustibles and fines residue. Building on these analyses, this study aims to explore the potential for improving the economy of LFM in Europe by creating value from these bulk process wastes. Specifically, the combustibles are treated through internal incineration with subsequent energy recovery, while fines residue is utilized as construction aggregates. Read More

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scGNN is a novel graph neural network framework for single-cell RNA-Seq analyses.

Nat Commun 2021 03 25;12(1):1882. Epub 2021 Mar 25.

Department of Electrical Engineering and Computer Science, and Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA.

Single-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell-cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. Read More

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Boosting the Photodynamic Degradation of Islet Amyloid Polypeptide Aggregates Via a "Bait-Hook-Devastate" Strategy.

ACS Appl Mater Interfaces 2021 Apr 25;13(13):14911-14919. Epub 2021 Mar 25.

National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

Photosensitizers that can generate reactive oxygen species (ROS) upon irradiation have emerged as promising agents for photodynamic degradation of toxic amyloid aggregates that are linked to many amyloidogenic diseases. However, due to the ultrastable β-sheet structure in amyloid aggregates and inefficient utilization of the generated ROS, it usually requires high stoichiometric concentration of the photosensitizer and/or intensive light irradiation to fully dissociate aggregates. In this work, we have developed a "bait-hook-devastate" strategy to boost the efficiency of the photodynamic degradation of amyloid aggregates. Read More

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Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem.

Front Mol Biosci 2020 8;7:558982. Epub 2021 Mar 8.

Department of Material and Bioprocess Engineering, School of Chemical Engineering, University of Campinas (UNICAMP), Campinas, Brazil.

Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) - the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. Read More

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TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6.

Acta Neuropathol Commun 2021 03 24;9(1):52. Epub 2021 Mar 24.

Department of Cellular and Molecular Biology, University of Arizona, 1007 E. Lowell St, LSS RM 548A, Tucson, AZ, 85721, USA.

Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications in Drosophila models of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Read More

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Platelet activation and aggregation in different centrifugal-flow left ventricular assist devices.

Platelets 2021 Mar 24:1-8. Epub 2021 Mar 24.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. Read More

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SGTA associates with intracellular aggregates in neurodegenerative diseases.

Mol Brain 2021 03 23;14(1):59. Epub 2021 Mar 23.

Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. Read More

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[Potential of Arbuscular Mycorrhizal Fungi, Biochar, and Combined Amendment on Sandy Soil Improvement Driven by Microbial Community].

Huan Jing Ke Xue 2021 Apr;42(4):2066-2079

Inner Mongolia Key Laboratory of Environmental Pollution Control and Waste Resource Recycle, Inner Mongolia Key Laboratory of Grassland Ecology, School of Ecology and Environment, Inner Mongolia University, Hohhot 010021, China.

Sandy soils are considered as a significant transition phase to desertification. The effective recovery of sandy soils is of great significance to mitigate the desertification process. Some studies have shown that arbuscular mycorrhizal (AM) fungi and biochar improved the sandy soil, but there have been very few studies regarding the combined effects of AM fungi and biochar amendments on sandy soil improvement. Read More

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