scholarly journals Structurally distinct external solvent-exposed domains drive replication of major human prions

2021 ◽  
Vol 17 (6) ◽  
pp. e1009642
Author(s):  
Mohammad Khursheed Siddiqi ◽  
Chae Kim ◽  
Tracy Haldiman ◽  
Miroslava Kacirova ◽  
Benlian Wang ◽  
...  
Keyword(s):  
Structural Organization ◽  
Structural Characteristics ◽  
Critical Role ◽  
Brain Structures ◽  
Propagation Rate ◽  
Seeding Rate ◽  
Prion Strains ◽  
Jakob Disease ◽  
Surface Domains ◽  
Hydroxyl Radical Footprinting

There is a limited understanding of structural attributes that encode the iatrogenic transmissibility and various phenotypes of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Here we report the detailed structural differences between major sCJD MM1, MM2, and VV2 prions determined with two complementary synchrotron hydroxyl radical footprinting techniques—mass spectrometry (MS) and conformation dependent immunoassay (CDI) with a panel of Europium-labeled antibodies. Both approaches clearly demonstrate that the phenotypically distant prions differ in a major way with regard to their structural organization, and synchrotron-generated hydroxyl radicals progressively inhibit their seeding potency in a strain and structure-specific manner. Moreover, the seeding rate of sCJD prions is primarily determined by strain-specific structural organization of solvent-exposed external domains of human prion particles that control the seeding activity. Structural characteristics of human prion strains suggest that subtle changes in the organization of surface domains play a critical role as a determinant of human prion infectivity, propagation rate, and targeting of specific brain structures.

scholarly journals Superior Alignment of Human iPSC-Osteoblasts Associated with Focal Adhesion Formation Stimulated by Oriented Collagen Scaffold

2021 ◽  
Vol 22 (12) ◽  
pp. 6232
Author(s):  
Ryosuke Ozasa ◽  
Aira Matsugaki ◽  
Tadaaki Matsuzaka ◽  
Takuya Ishimoto ◽  
Hui-Suk Yun ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Structural Organization ◽  
Critical Role ◽  
Bone Matrix ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Collagen Scaffold ◽  
Patient Specific ◽  
Specific Cell ◽  
Adhesion Behavior

Human-induced pluripotent stem cells (hiPSCs) can be applied in patient-specific cell therapy to regenerate lost tissue or organ function. Anisotropic control of the structural organization in the newly generated bone matrix is pivotal for functional reconstruction during bone tissue regeneration. Recently, we revealed that hiPSC-derived osteoblasts (hiPSC-Obs) exhibit preferential alignment and organize in highly ordered bone matrices along a bone-mimetic collagen scaffold, indicating their critical role in regulating the unidirectional cellular arrangement, as well as the structural organization of regenerated bone tissue. However, it remains unclear how hiPSCs exhibit the cell properties required for oriented tissue construction. The present study aimed to characterize the properties of hiPSCs-Obs and those of their focal adhesions (FAs), which mediate the structural relationship between cells and the matrix. Our in vitro anisotropic cell culture system revealed the superior adhesion behavior of hiPSC-Obs, which exhibited accelerated cell proliferation and better cell alignment along the collagen axis compared to normal human osteoblasts. Notably, the oriented collagen scaffold stimulated FA formation along the scaffold collagen orientation. This is the first report of the superior cell adhesion behavior of hiPSC-Obs associated with the promotion of FA assembly along an anisotropic scaffold. These findings suggest a promising role for hiPSCs in enabling anisotropic bone microstructural regeneration.

Genetic Creutzfeldt–Jakob disease‐M232R with the cooccurrence of multiple prion strains, M1 +  M2C +  M2T : Report of an autopsy case

2021 ◽  
Author(s):  
Masayuki Shintaku ◽  
Takeshi Nakamura ◽  
Daita Kaneda ◽  
Akiyo Shinde ◽  
Hirofumi Kusaka ◽  
...  
Keyword(s):  
Autopsy Case ◽  
Prion Strains ◽  
Jakob Disease

scholarly journals The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1357
Author(s):  
Andreea-Mariana Negrescu ◽  
Anisoara Cimpean
Keyword(s):  
Foreign Bodies ◽  
Structural Characteristics ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Bioactive Molecules ◽  
New Bone Formation ◽  
Recent Developments

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

scholarly journals Critical role of spectrin in hearing development and deafness

2019 ◽  
Vol 5 (4) ◽  
pp. eaav7803 ◽  
Author(s):  
Yan Liu ◽  
Jieyu Qi ◽  
Xin Chen ◽  
Mingliang Tang ◽  
Cenfeng Chu ◽  
...  
Keyword(s):  
Hair Cells ◽  
Knockout Mice ◽  
Crucial Role ◽  
Structural Organization ◽  
Critical Role ◽  
Super Resolution ◽  
Mechanical Vibrations ◽  
Hearing Ability ◽  
Profound Deafness

Inner ear hair cells (HCs) detect sound through the deflection of mechanosensory stereocilia. Stereocilia are inserted into the cuticular plate of HCs by parallel actin rootlets, where they convert sound-induced mechanical vibrations into electrical signals. The molecules that support these rootlets and enable them to withstand constant mechanical stresses underpin our ability to hear. However, the structures of these molecules have remained unknown. We hypothesized that αII- and βII-spectrin subunits fulfill this role, and investigated their structural organization in rodent HCs. Using super-resolution fluorescence imaging, we found that spectrin formed ring-like structures around the base of stereocilia rootlets. These spectrin rings were associated with the hearing ability of mice. Further, HC-specific, βII-spectrin knockout mice displayed profound deafness. Overall, our work has identified and characterized structures of spectrin that play a crucial role in mammalian hearing development.

scholarly journals Shared and Unique Roles of Cap23 and Gap43 in Actin Regulation, Neurite Outgrowth, and Anatomical Plasticity

2000 ◽  
Vol 149 (7) ◽  
pp. 1443-1454 ◽  
Author(s):  
Dunja Frey ◽  
Thorsten Laux ◽  
Lan Xu ◽  
Corinna Schneider ◽  
Pico Caroni
Keyword(s):  
Actin Cytoskeleton ◽  
Neurite Outgrowth ◽  
Critical Role ◽  
Brain Structures ◽  
Calmodulin Binding ◽  
Essentially Normal ◽  
Anatomical Plasticity ◽  
Nerve Sprouting

CAP23 is a major cortical cytoskeleton–associated and calmodulin binding protein that is widely and abundantly expressed during development, maintained in selected brain structures in the adult, and reinduced during nerve regeneration. Overexpression of CAP23 in adult neurons of transgenic mice promotes nerve sprouting, but the role of this protein in process outgrowth was not clear. Here, we show that CAP23 is functionally related to GAP43, and plays a critical role to regulate nerve sprouting and the actin cytoskeleton. Knockout mice lacking CAP23 exhibited a pronounced and complex phenotype, including a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction. This sprouting deficit was rescued by transgenic overexpression of either CAP23 or GAP43 in adult motoneurons. Knockin mice expressing GAP43 instead of CAP23 were essentially normal, indicating that, although these proteins do not share homologous sequences, GAP43 can functionally substitute for CAP23 in vivo. Cultured sensory neurons lacking CAP23 exhibited striking alterations in neurite outgrowth that were phenocopied by low doses of cytochalasin D. A detailed analysis of such cultures revealed common and unique functions of CAP23 and GAP43 on the actin cytoskeleton and neurite outgrowth. The results provide compelling experimental evidence for the notion that CAP23 and GAP43 are functionally related intrinsic determinants of anatomical plasticity, and suggest that these proteins function by locally promoting subplasmalemmal actin cytoskeleton accumulation.

scholarly journals Deep melting reveals liquid structural memory and anomalous ferromagnetism in bismuth

2017 ◽  
Vol 114 (13) ◽  
pp. 3375-3380 ◽  
Author(s):  
Yu Shu ◽  
Dongli Yu ◽  
Wentao Hu ◽  
Yanbin Wang ◽  
Guoyin Shen ◽  
...  
Keyword(s):  
High Temperature ◽  
Low Temperature ◽  
Electrical Resistance ◽  
Structural Characteristics ◽  
Critical Role ◽  
Melting Curve ◽  
Molten State ◽  
Pressure Independent ◽  
Temperature Liquid ◽  
Structural Memory

As an archetypal semimetal with complex and anisotropic Fermi surface and unusual electric properties (e.g., high electrical resistance, large magnetoresistance, and giant Hall effect), bismuth (Bi) has played a critical role in metal physics. In general, Bi displays diamagnetism with a high volumetric susceptibility (∼10−4). Here, we report unusual ferromagnetism in bulk Bi samples recovered from a molten state at pressures of 1.4–2.5 GPa and temperatures above ∼1,250 K. The ferromagnetism is associated with a surprising structural memory effect in the molten state. On heating, low-temperature Bi liquid (L) transforms to a more randomly disordered high-temperature liquid (L′) around 1,250 K. By cooling from above 1,250 K, certain structural characteristics of liquid L′ are preserved in L. Bi clusters with characteristics of the liquid L′ motifs are further preserved through solidification into the Bi-II phase across the pressure-independent melting curve, which may be responsible for the observed ferromagnetism.

scholarly journals What Neuroscientific Studies Tell Us about Inhibition of Return

Vision ◽  
2019 ◽  
Vol 3 (4) ◽  
pp. 58 ◽  
Author(s):  
Jason Satel ◽  
Nicholas R. Wilson ◽  
Raymond M. Klein
Keyword(s):  
Inhibition Of Return ◽  
Brain Activity ◽  
Critical Role ◽  
Direct Methods ◽  
Brain Structures ◽  
Developmental Studies ◽  
Unit Recording ◽  
Wide Range ◽  
Lesion Studies

An inhibitory aftermath of orienting, inhibition of return (IOR), has intrigued scholars since its discovery about 40 years ago. Since then, the phenomenon has been subjected to a wide range of neuroscientific methods and the results of these are reviewed in this paper. These include direct manipulations of brain structures (which occur naturally in brain damage and disease or experimentally as in TMS and lesion studies) and measurements of brain activity (in humans using EEG and fMRI and in animals using single unit recording). A variety of less direct methods (e.g., computational modeling, developmental studies, etc.) have also been used. The findings from this wide range of methods support the critical role of subcortical and cortical oculomotor pathways in the generation and nature of IOR.

P300 event-related potential and serotonin-1A activity in depression

1999 ◽  
Vol 14 (3) ◽  
pp. 143-147 ◽  
Author(s):  
M Hansenne ◽  
M Ansseau
Keyword(s):  
Critical Role ◽  
Brain Structures ◽  
Significant Negative Correlation ◽  
Event Related Potential ◽  
P300 Amplitude ◽  
P300 Latency ◽  
Endocrine Response ◽  
Major Depressive ◽  
Serotonergic Activity ◽  
The Brain

SummaryThe identification of the brain structures and neurotransmitters responsible for the generation and/or modulation of P300 could lead to important clinical implications. Since serotonin disturbances seem to play a critical role in depression, the aim of the study was to assess the possible relationships between the P300 event-related brain potential and serotonergic activity in depression. The study was conducted among 45 major depressive inpatients, and serotonergic activity was assessed by prolactin (PRL) response to flesinoxan (a 5-HT1A agonist). Results showed a significant negative correlation between P300 amplitude and PRL response to flesinoxan (r = –0.40, P = 0.007 at Cz; r = –0.47, P = 0.001 at Pz). In contrast, both P300 latency and reaction time were not related to endocrine response. This study supports a role for serotonin-1A in the neurobiological modulation of P300 amplitude.

scholarly journals Neuroinvasion in Prion Diseases: The Roles of Ascending Neural Infection and Blood Dissemination

2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Sílvia Sisó ◽  
Lorenzo González ◽  
Martin Jeffrey
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prion Protein ◽  
Prion Diseases ◽  
Autonomic Nerves ◽  
Peripheral Organs ◽  
Prion Strains ◽  
New Variant ◽  
Jakob Disease ◽  
The Central Nervous System

Prion disorders are infectious, neurodegenerative diseases that affect humans and animals. Susceptibility to some prion diseases such as kuru or the new variant of Creutzfeldt-Jakob disease in humans and scrapie in sheep and goats is influenced by polymorphisms of the coding region of the prion protein gene, while other prion disorders such as fatal familial insomnia, familial Creutzfeldt-Jakob disease, or Gerstmann-Straussler-Scheinker disease in humans have an underlying inherited genetic basis. Several prion strains have been demonstrated experimentally in rodents and sheep. The progression and pathogenesis of disease is influenced by both genetic differences in the prion protein and prion strain. Some prion diseases only affect the central nervous system whereas others involve the peripheral organs prior to neuroinvasion. Many experiments undertaken in different species and using different prion strains have postulated common pathways of neuroinvasion. It is suggested that prions access the autonomic nerves innervating peripheral organs and tissues to finally reach the central nervous system. We review here published data supporting this view and additional data suggesting that neuroinvasion may concurrently or independently involve the blood vascular system.

Twisted Nanostructures of 2H-MoS2 Slabs

2009 ◽  
Vol 1217 ◽  
Author(s):  
Manuel Ramos ◽  
Domingo A. Ferrer ◽  
Miguel José-Yacamán ◽  
Gilles Berhault ◽  
Brenda Torres ◽  
...  
Keyword(s):  
Structural Organization ◽  
Structural Model ◽  
Structural Characteristics ◽  
Metal Sulfide ◽  
Local Information ◽  
Important Class ◽  
Transition Metal Sulfide ◽  
Layered Transition Metal ◽  
Simulated Images ◽  
Nanoscale Level

AbstractIn the last decades, HRTEM approach has been quite fruitful to study structural characteristics of layered transition metal sulfide (LTMS) catalytic materials since providing direct local information about the structural organization of this quite important class of catalysts at the nanoscale level. However, up to now, HRTEM observations of some common localized structural organization like honeycomb-like structures have remained unexplained. In the present study, a structural model corresponding to stacked 2H-MoS2 slabs twisted along their basal direction is proposed to explain honeycomb like-structures observed by HRTEM. This model is based on a comparison between experimental and simulated images of 2H-MoS2 catalysts promoted with cobalt. The resulting Density of States (DOS) of the twisted structure was then calculated.

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