scholarly journals Tracing in Vivo the Dorsal Loop of the Optic Radiation: Convergent Perspectives From Tractography and Electrophysiology Compared to a Neuroanatomical Ground Truth.

2021 ◽  
Author(s):  
Michele Rizzi ◽  
Ivana Sartori ◽  
Maria Del Vecchio ◽  
Flavia Maria Zauli ◽  
Luca Berta ◽  
...  
Keyword(s):  
White Matter ◽  
Ground Truth ◽  
Optic Radiation ◽  
Individual Patient Level ◽  
Geometrical Properties ◽  
Functional Richness ◽  
Neurophysiological Data ◽  
The Individual ◽  
And Function

Abstract The temporo-parietal junction (TPJ) is a cortical area contributing to a multiplicity of visual, language-related and cognitive functions. In line with this functional richness, also the organization of the underlying white matter is highly complex and includes several bundles. The few studies tackling to date the outcome and neurological burdens of surgical operations addressing TPJ document the presence of language disturbances and visual field damages, with the latter hardly recovered in time. This observation advocates for procedures identifying the optic radiation (OR) bundles crossing the white matter (WM) below TPJ. In the present study we adopted a multimodal approach to address the anatomo-functional correlates of the dorsal loop (DL) of the OR. In particular, we combined cadavers’ dissection with tractographic and electrophysiological data collected in drug-resistant epileptic patients explored by stereoelectroencephalography (SEEG). Cadaver dissection allowed us to appreciate the position and geometrical properties of the DL. More surprisingly, both tractographic and electrophysiological observations converged on a unitary picture highly coherent with the data obtained by neuroanatomical observation.The combination of diverse and multimodal observations allows to overcome the limitations intrinsic to single methodologies, and to define a unitary picture which makes it possible to investigate DL presurgically and at the individual patient level, aiming at limiting the postsurgical damages. Notwithstanding, such a combined approach could serve as a model of investigation for future neuroanatomical inquiries tackling WM fibers anatomy and function through SEEG-derived neurophysiological data.

scholarly journals Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder

2019 ◽  
Vol 45 (6) ◽  
pp. 1367-1378 ◽  
Author(s):  
Ellen Ji ◽  
Pamela Guevara ◽  
Miguel Guevara ◽  
Antoine Grigis ◽  
Nicole Labra ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Language Processing ◽  
Structural Connectivity ◽  
Anterior Cingulate ◽  
Precentral Gyrus ◽  
Psychiatric Illnesses ◽  
And Function ◽  
Post Hoc

Abstract Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes,” with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

scholarly journals Posttranslational Modifications and the Immunogenicity of Biotherapeutics

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Roy Jefferis
Keyword(s):  
Posttranslational Modifications ◽  
Drug Product ◽  
Molecular Forms ◽  
Phagocytic Cells ◽  
Production Platform ◽  
The Individual ◽  
And Function ◽  
Antigen Presenting

Whilst the amino acid sequence of a protein is determined by its gene sequence, the final structure and function are determined by posttranslational modifications (PTMs), including quality control (QC) in the endoplasmic reticulum (ER) and during passage through the Golgi apparatus. These processes are species and cell specific and challenge the biopharmaceutical industry when developing a production platform for the generation of recombinant biologic therapeutics. Proteins and glycoproteins are also subject to chemical modifications (CMs) bothin vivoandin vitro. The individual is naturally tolerant to molecular forms of self-molecules but nonself variants can provoke an immune response with the generation of anti-drug antibodies (ADA); aggregated forms can exhibit enhanced immunogenicity and QC procedures are developed to avoid or remove them. Monoclonal antibody therapeutics (mAbs) are a special case because their purpose is to bind the target, with the formation of immune complexes (ICs), a particular form of aggregate. Such ICs may be removed by phagocytic cells that have antigen presenting capacity. These considerations may frustrate the possibility of ameliorating the immunogenicity of mAbs by rigorous exclusion of aggregates from drug product. Alternate strategies for inducing immunosuppression or tolerance are discussed.

Left ventricular volumes and function in the embryonic mouse heart

1997 ◽  
Vol 273 (3) ◽  
pp. H1368-H1376 ◽  
Author(s):  
N. Tanaka ◽  
L. Mao ◽  
F. A. DeLano ◽  
E. M. Sentianin ◽  
K. R. Chien ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Fluorescent Imaging ◽  
Left Ventricular Volumes ◽  
Mouse Heart ◽  
Embryonic Mouse ◽  
End Diastolic Volume ◽  
Or Gene ◽  
The Individual ◽  
And Function

This study describes miniaturized technology for the in vivo analysis of the volume and function of the embryonic mouse heart and the application of this technology to study the normal embryonic left ventricle (LV) at two stages of development. With the use of microsurgical techniques, embryos from embryonic day (ED) 10.5 (ED10.5) to ED16 were delivered individually from litters of normal dams, and cardiac visualization was achieved with the use of intravital microscopy by transillumination, with the umbilical circulation intact. At ED10.5-11, the heart could be imaged in color in the intact embryo, whereas at ED12.5 it was necessary to open the chest; at ED13.5-14.5, fluorescent imaging with the use of microinjection of fluorescein-conjugated albumin was necessary to visualize the LV chamber. At ED10.5-11, the LV end-diastolic volumes averaged 0.16 microliter (n = 14), and at ED13.5-14.5, they averaged 0.57 microliter (n = 16). At both ages there was a positive linear relationship between the LV end-diastolic volume and the stroke volume despite substantial variations in individual heart rates, reflecting the relative uniformity of the LV ejection fractions within each age group. The average of the individual ejection fractions was 27.4% at ED10.5-11 and 58.4% at ED13.5-14.5, the latter being within the normal range for the adult rodent heart. These methods will be useful for assessing in vivo cardiac function at ED10.5 and older murine embryos in litters of transgenic or gene-targeted mice when the mutation leads to later embryonic lethality.

scholarly journals The Lyt-2 molecule recognizes residues in the class I alpha 3 domain in allogeneic cytotoxic T cell responses.

1988 ◽  
Vol 168 (1) ◽  
pp. 325-341 ◽  
Author(s):  
J M Connolly ◽  
T A Potter ◽  
E M Wormstall ◽  
T H Hansen
Keyword(s):  
Primary Response ◽  
Class I ◽  
Single Amino Acid ◽  
Cytotoxic T Cell ◽  
Mhc Class I Molecule ◽  
Cytotoxic T Cell Responses ◽  
The Individual ◽  
And Function

The involvement of the different domains of the MHC class I molecule in CTL recognition was investigated. mAbs specific for the alpha 1/alpha 2 domains of H-2Ld interfered with both the primary and secondary generation and effector function of in vitro Ld-specific CTL. mAbs specific for the alpha 3 domain of H-2Ld interfered with the generation and function of primary in vitro Ld-specific CTL; however, there was no effect on the in vitro generation of secondary CTL and only partial inhibition of their function. In vivo treatment with graft-specific antibodies to both the alpha 3 domain and the alpha 1/alpha 2 domains together resulted in a dramatic enhancement of Ld- or Dd-disparate skin grafts, whereas the individual mAbs showed minimal effects. This suggested that the class I alpha 3 domain is recognized by alloreactive CTL. Several approaches were undertaken to examine whether recognition of the alpha 3 domain determinants is mediated by the Lyt-2 molecule. When mAbs specific for the alpha 3 domain of either H-2Ld or H-2Dd were used in vivo and in vitro, the resulting CTL population was not inhibited by antibody to the alpha 3 domain and was only partially inhibited by antibody to Lyt-2. We therefore observed a correlation between the effects of antibody to the class I alpha 3 domain of the target molecule and antibody to the Lyt-2 molecule on the CTL. To further test the relationship between CTL recognition of the alpha 3 domain and the involvement of Lyt-2, we used a cell expressing a mutation in the alpha 3 domain of the Dd molecule. The mutation resulted in a single amino acid substitution of glu to lys at residue 227 of the alpha 3 domain. Consistent with an earlier report, cells expressing the mutant Dd lys molecule were not lysed by CTL from a primary stimulation against the wild-type Dd glu molecule. However, this same cell line was killed by the Lyt-2-independent secondary Dd-specific CTL generated in the presence of antibody to the alpha 3 domain in vivo and in vitro. Furthermore, cells expressing the mutant Dd lys molecule failed to stimulate a primary response. In conclusion, several independent lines of evidence indicate that residues in the alpha 3 domain of the class I molecule are involved in recognition by the Lyt-2 molecule, and that Lyt-2-mediated recognition can be specifically blocked using mAb to determinants in the alpha 3 domain.

scholarly journals Disturbances in White Matter Integrity in the Ultra-High-Risk Psychosis State—A Systematic Review

2021 ◽  
Vol 10 (11) ◽  
pp. 2515
Author(s):  
Katarzyna Waszczuk ◽  
Katarzyna Rek-Owodziń ◽  
Ernest Tyburski ◽  
Monika Mak ◽  
Błażej Misiak ◽  
...  
Keyword(s):  
White Matter ◽  
High Risk ◽  
Diffusion Tensor ◽  
Schizophrenia Spectrum Disorders ◽  
Schizophrenia Spectrum ◽  
Inferior Longitudinal Fasciculus ◽  
Ultra High Risk ◽  
Recent Developments ◽  
And Function

Schizophrenia is a severe and disabling mental illness whose etiology still remains unclear. The available literature indicates that there exist white matter (WM) abnormalities in people with schizophrenia spectrum disorders. Recent developments in modern neuroimaging methods have enabled the identification of the structure, morphology, and function of the underlying WM fibers in vivo. The purpose of this paper is to review the existing evidence about WM abnormalities in individuals at ultra-high risk of psychosis (UHR) with the use of diffusion tensor imaging (DTI) available from the National Center for Biotechnology Information PubMed (Medline) and Health Source: Nursing/Academic Edition databases. Of 358 relevant articles identified, 25 papers published in the years 2008–2020 were ultimately included in the review. Most of them supported the presence of subtle aberrations in WM in UHR individuals, especially in the superior longitudinal fasciculus (SLF), the inferior longitudinal fasciculus (ILF), and the inferior fronto-occipital fasciculus (IFOF). These alterations may therefore be considered a promising neurobiological marker for the risk of psychosis. However, due to methodological discrepancies and the relative scarcity of evidence, further investigation is called for, especially into connectome analysis in UHR patients.

scholarly journals The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Marta Boccazzi ◽  
Juliette Van Steenwinckel ◽  
Anne-Laure Schang ◽  
Valérie Faivre ◽  
Tifenn Le Charpentier ◽  
...  
Keyword(s):  
White Matter ◽  
Primary Cultures ◽  
White Matter Injury ◽  
Poly I:C ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Preterm Born ◽  
And Function

AbstractA leading cause of preterm birth is the exposure to systemic inflammation (maternal/fetal infection), which leads to neuroinflammation and white matter injury (WMI). A wide range of cytokines and chemokines are expressed and upregulated in oligodendrocytes (OLs) in response to inflammation and numerous reports show that OLs express several receptors for immune related molecules, which enable them to sense inflammation and to react. However, the role of OL immune response in WMI is unclear. Here, we focus our study on toll-like receptor-3 (TLR3) that is activated by double-strand RNA (dsRNA) and promotes neuroinflammation. Despite its importance, its expression and role in OLs remain unclear. We used an in vivo mouse model, which mimics inflammation-mediated WMI of preterm born infants consisting of intraperitoneal injection of IL-1β from P1 to P5. In the IL-1β-treated animals, we observed the upregulation of Tlr3, IL-1β, IFN-β, Ccl2, and Cxcl10 in both PDGFRα+ and O4+ sorted cells. This upregulation was higher in O4+ immature OLs (immOLs) as compared to PDGFRα+ OL precursor cells (OPCs), suggesting a different sensitivity to neuroinflammation. These observations were confirmed in OL primary cultures: cells treated with TLR3 agonist Poly(I:C) during differentiation showed a stronger upregulation of Ccl2 and Cxcl10 compared to cells treated during proliferation and led to decreased expression of myelin genes. Finally, OLs were able to modulate microglia phenotype and function depending on their maturation state as assessed by qPCR using validated markers for immunomodulatory, proinflammatory, and anti-inflammatory phenotypes and by phagocytosis and morphological analysis. These results show that during inflammation the response of OLs can play an autonomous role in blocking their own differentiation: in addition, the immune activation of OLs may play an important role in shaping the response of microglia during inflammation.

scholarly journals Increased and decreased superficial white matter structural connectivity in schizophrenia and bipolar disorder

2018 ◽  
Author(s):  
Ellen Ji ◽  
Pamela Guevara ◽  
Miguel Guevara ◽  
Antoine Grigis ◽  
Nicole Labra ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Language Processing ◽  
Structural Connectivity ◽  
Anterior Cingulate ◽  
Precentral Gyrus ◽  
Psychiatric Illnesses ◽  
And Function ◽  
Post Hoc

AbstractSchizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes”, with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from post-mortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labelling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

scholarly journals Bilirubin and its Oxidation Products Damage Brain White Matter

2014 ◽  
Vol 34 (11) ◽  
pp. 1837-1847 ◽  
Author(s):  
Katarina Lakovic ◽  
Jinglu Ai ◽  
Josephine D'Abbondanza ◽  
Asma Tariq ◽  
Mohammed Sabri ◽  
...  
Keyword(s):  
White Matter ◽  
Dimethyl Sulfoxide ◽  
Brain Slices ◽  
Structure And Function ◽  
Adult Brain ◽  
Oxidation Products ◽  
Unmyelinated Axons ◽  
And Function

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke.

scholarly journals Unraveling the mechanism of the cadherin-catenin-actin catch bond

2018 ◽  
Author(s):  
Shishir Adhikari ◽  
Jacob Moran ◽  
Christopher Weddle ◽  
Michael Hinczewski
Keyword(s):  
Protein Complexes ◽  
Optical Tweezer ◽  
Force Transducer ◽  
Salt Bridges ◽  
Lifetime Distributions ◽  
Catch Bond ◽  
The Individual ◽  
And Function

The adherens junctions between epithelial cells involve a protein complex formed by E-cadherin, β-catenin, α-catenin and F-actin. The stability of this complex was a puzzle for many years, since in vitro studies could reconstitute various stable subsets of the individual proteins, but never the entirety. The missing ingredient turned out to be mechanical tension: a recent experiment that applied physiological forces to the complex with an optical tweezer dramatically increased its lifetime, a phenomenon known as catch bonding. However, in the absence of a crystal structure for the full complex, the microscopic details of the catch bond mechanism remain mysterious. Building on structural clues that point to α-catenin as the force transducer, we present a quantitative theoretical model for how the catch bond arises, fully accounting for the experimental lifetime distributions. The model allows us to predict the energetic changes induced by tension at the interface between α-catenin and F-actin. It also identifies a significant energy barrier due to a network of salt bridges between two conformational states of β-catenin. By stabilizing one of these states, this barrier could play a role in how the complex responds to additional in vivo binding partners like vinculin. Since significant conformational energy barriers are a common feature of other adhesion systems that exhibit catch bonds, our model can be adapted into a general theoretical framework for integrating structure and function in a variety of force-regulated protein complexes.

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography

2007 ◽  
Vol 102 (5) ◽  
pp. 2046-2055 ◽  
Author(s):  
N. L. Ford ◽  
E. L. Martin ◽  
J. F. Lewis ◽  
R. A. W. Veldhuizen ◽  
M. Drangova ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Tidal Volume ◽  
Human Subjects ◽  
Free Breathing ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Lung Morphology ◽  
The Individual ◽  
And Function

Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 ± 0.03 ml) and functional residual capacity (0.16 ± 0.03 ml).

Sign in / Sign up

Export Citation Format

Share Document