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1.
Front Mol Biosci ; 11: 1321364, 2024.
Article in English | MEDLINE | ID: mdl-38584701

ABSTRACT

Lipid nanoparticles (LNPs) are being intensively researched and developed to leverage their ability to safely and effectively deliver therapeutics. To achieve optimal therapeutic delivery, a comprehensive understanding of the relationship between formulation, structure, and efficacy is critical. However, the vast chemical space involved in the production of LNPs and the resulting structural complexity make the structure to function relationship challenging to assess and predict. New components and formulation procedures, which provide new opportunities for the use of LNPs, would be best identified and optimized using high-throughput characterization methods. Recently, a high-throughput workflow, consisting of automated mixing, small-angle X-ray scattering (SAXS), and cellular assays, demonstrated a link between formulation, internal structure, and efficacy for a library of LNPs. As SAXS data can be rapidly collected, the stage is set for the collection of thousands of SAXS profiles from a myriad of LNP formulations. In addition, correlated LNP small-angle neutron scattering (SANS) datasets, where components are systematically deuterated for additional contrast inside, provide complementary structural information. The centralization of SAXS and SANS datasets from LNPs, with appropriate, standardized metadata describing formulation parameters, into a data repository will provide valuable guidance for the formulation of LNPs with desired properties. To this end, we introduce Simple Scattering, an easy-to-use, open data repository for storing and sharing groups of correlated scattering profiles obtained from LNP screening experiments. Here, we discuss the current state of the repository, including limitations and upcoming changes, and our vision towards future usage in developing our collective knowledge base of LNPs.

2.
Nat Commun ; 15(1): 3413, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649740

ABSTRACT

The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.


Subject(s)
Biomolecular Condensates , Molecular Dynamics Simulation , Scattering, Small Angle , Biomolecular Condensates/chemistry , Fluorescence Recovery After Photobleaching , Neutron Diffraction , Macromolecular Substances/chemistry , Proteins/chemistry
3.
Article in English | MEDLINE | ID: mdl-38442043

ABSTRACT

OBJECTIVE: A pathological tremor (PT) is an involuntary rhythmic movement of varying frequency and amplitude that affects voluntary motion, thus compromising individuals' independence. A comprehensive model incorporating PT's physiological and biomechanical aspects can enhance our understanding of the disorder and provide valuable insights for therapeutic approaches. This study aims to build a biomechanical model of pathological tremors using OpenSim's realistic musculoskeletal representation of the human wrist with two degrees of freedom. METHODS: We implemented a Matlab/OpenSim interface for a forward dynamics simulation, which allows for the modeling, simulation, and design of a physiological H∞ closed-loop control. This system replicates pathological tremors similar to those observed in patients when their arm is extended forward, the wrist is pronated, and the hand is subject to gravity forces. The model was individually tuned to five subjects (four Parkinson's disease patients and one diagnosed with essential tremor), each exhibiting distinct tremor characteristics measured by an inertial sensor and surface EMG electrodes. Simulation agreement with the experiments for EMGs, central frequency, joint angles, and angular velocities were evaluated by Jensen-Shannon divergence, histogram centroid error, and histogram intersection. RESULTS: The model emulated individual tremor statistical characteristics, including muscle activations, frequency, variability, and wrist kinematics, with greater accuracy for the four Parkinson's patients than the essential tremor. CONCLUSION: The proposed model replicated the main statistical features of subject-specific wrist tremor kinematics. SIGNIFICANCE: Our methodology may facilitate the design of patient-specific rehabilitation devices for tremor suppression, such as neural prostheses and electromechanical orthoses.


Subject(s)
Dyskinesias , Essential Tremor , Parkinson Disease , Humans , Tremor , Wrist/physiology , Wrist Joint , Biomechanical Phenomena
4.
bioRxiv ; 2024 Feb 11.
Article in English | MEDLINE | ID: mdl-37873180

ABSTRACT

The functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.

5.
J Invest Dermatol ; 144(4): 833-843.e3, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37951348

ABSTRACT

Human Langerhans cells highly express CD1a antigen-presenting molecules. To understand the functions of CD1a in human skin, we used CD1a tetramers to capture T cells and determine their effector functions and TCR patterns. Skin T cells from all donors showed CD1a tetramer staining, which in three cases exceeded 10% of skin T cells. CD1a tetramer-positive T cells produced diverse cytokines, including IL-2, IL-4, IL-5, IL-9, IL-17, IL-22, and IFN-γ. Conserved TCRs often recognize nonpolymorphic antigen-presenting molecules, but no TCR motifs are known for CD1a. We detected highly conserved TCRs that used TRAV34 and TRBV28 variable genes, which is a known motif for recognition of staphylococcal enterotoxin B, a superantigen associated with atopic dermatitis. We found that these conserved TCRs did not respond to superantigen presented by CD1a, but instead showed a cross-reactive response with two targets: CD1a and staphylococcal enterotoxin B presented by classical major histocompatibility complex II. These studies identify a conserved human TCR motif for CD1a-reactive T cells. Furthermore, the demonstrated cross-reaction of T cells with two common skin-specific stimuli suggests a candidate mechanism by which CD1a and skin flora could synergize during natural immune response and in Staphylococcus-associated skin diseases.


Subject(s)
Antigens, CD1 , Staphylococcal Skin Infections , Superantigens , Humans , T-Lymphocytes , Enterotoxins , Receptors, Antigen, T-Cell , Staphylococcus
6.
Res Sq ; 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37886520

ABSTRACT

The functions of biomolecular condensates are thought to be influenced by their material properties, and these are in turn determined by the multiscale structural features within condensates. However, structural characterizations of condensates are challenging, and hence rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and bespoke coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that mimic nucleolar granular components (GCs). We show that facsimiles of GCs are network fluids featuring spatial inhomogeneities across hierarchies of length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights, extracted from a combination of approaches, suggest that condensates formed by multivalent proteins share features with network fluids formed by associative systems such as patchy or hairy colloids.

7.
J Phys Chem Lett ; 13(42): 9834-9840, 2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36250687

ABSTRACT

Bicelles, composed of a mixture of long and short chain lipids, form nanostructured molecular assemblies that are attractive lipid-membrane mimics for in vitro studies of integral membrane proteins. Here we study the effect of a third component, the single chain detergent n-dodecyl-ß-d-maltoside (DDM) on the morphology of bicelles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO) below (10 °C) and above (38 °C) the phase transition. In the absence of DDM, bicelles convert from ellipsoidal disks at 10 °C to extended ribbon-like structures at 38 °C. The addition of DDM reshapes the ellipsoidal disc to a circular one and the flattened ribbon to a circular-cylinder worm-like micelle. Knowledge of the influence of the single chain detergent DDM on bicelle nanoscale morphology contributes toward comprehending lipid membrane self-organization and to the goal of optimizing lipid mimics for membrane biology research.


Subject(s)
Dimyristoylphosphatidylcholine , Micelles , Dimyristoylphosphatidylcholine/chemistry , Detergents , Bile Acids and Salts , Phosphorylcholine , Membrane Proteins/chemistry , Lipid Bilayers/chemistry
8.
BMC Public Health ; 22(1): 83, 2022 01 13.
Article in English | MEDLINE | ID: mdl-35027014

ABSTRACT

Interventions that increase population physical activity are required to promote health and wellbeing. parkrun delivers community-based, 5 km events worldwide yet 43% who register never participate in a parkrun event. This research had two objectives; i) explore the demographics of people who register for parkrun in United Kingdom, Australia, Ireland, and don't initiate or maintain participation ii) understand the barriers to participating in parkrun amongst these people. Mandatory data at parkrun registration provided demographic characteristics of parkrun registrants. A bespoke online survey distributed across the three countries captured the reasons for not participating or only participating once. Of 680,255 parkrun registrants between 2017 and 19, 293,542 (43%) did not participate in any parkrun events and 147,148 (22%) only participated in one parkrun event. Females, 16-34 years and physically inactive were more likely to not participate or not return to parkrun. Inconvenient start time was the most frequently reported barrier to participating, with females more likely than males to report the psychological barrier of feeling too unfit to participate. Co-creating strategies with and for people living with a chronic disease, women, young adults, and physically inactive people, could increase physical activity participation within parkrun.


Subject(s)
Exercise , Health Promotion , Australia , Female , Humans , Male , Surveys and Questionnaires , United Kingdom , Young Adult
9.
Mult Scler Relat Disord ; 57: 103422, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34871858

ABSTRACT

We characterized the frequency of diffusely abnormal white matter (DAWM) across a broad spectrum of multiple sclerosis (MS) participants. 35% of clinically isolated syndrome (CIS), 57% of relapsing remitting and 64% of secondary progressive MS participants demonstrated DAWM. CIS with DAWM had decreased cortical thickness, higher lesion load and a higher concentration of serum neurofilament light chain compared to CIS without DAWM. DAWM may be useful in identifying CIS patients with greater injury to their brains. Larger and longitudinal studies are warranted.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , White Matter , Brain/diagnostic imaging , Humans , Intermediate Filaments , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , White Matter/diagnostic imaging
10.
Food Chem ; 365: 130474, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34265645

ABSTRACT

An analytical procedure for the multielement determination in enteral nutrition formulations employing slurry sampling and inductively coupled plasma optical emission spectrometry (ICP OES) is proposed. A two-level full-factorial design was applied to assess the influence of the presence of stabilizing agents (HNO3, Triton X-100 and ethanol) on the composition of the slurry. Multiple response was established as a dependent variable. The experimental conditions for the preparation of the slurry were: 2.0 mL of sample and 8.0 mL of 10% (v/v) HNO3. The limits of detection (LOD) were 5; 9; and 10 µg L-1 for Cu, Fe, Zn, respectively. For P, and K, the LOD were 8 and 24 mg L-1, respectively. The method was applied for the analysis of three enteral nutrition formulation samples and the obtained concentrations ranges were (in mg L-1): 0.41-0.43 (Cu), 2.0-2.9 (Fe), 1.7-3.1 (Zn), 682-1409 (K), and 217-344 (P).


Subject(s)
Enteral Nutrition , Limit of Detection , Spectrum Analysis
11.
J Phys Chem Lett ; 12(23): 5608-5615, 2021 Jun 17.
Article in English | MEDLINE | ID: mdl-34110168

ABSTRACT

Papain-like protease (PLpro) from SARS-CoV-2 plays essential roles in the replication cycle of the virus. In particular, it preferentially interacts with and cleaves human interferon-stimulated gene 15 (hISG15) to suppress the innate immune response of the host. We used small-angle X-ray and neutron scattering combined with computational techniques to study the mechanism of interaction of SARS-CoV-2 PLpro with hISG15. We showed that hISG15 undergoes a transition from an extended to a compact state after binding to PLpro, a conformation that has not been previously observed in complexes of SARS-CoV-2 PLpro with ISG15 from other species. Furthermore, computational analysis showed significant conformational flexibility in the ISG15 N-terminal domain, suggesting that it is weakly bound to PLpro and supports a binding mechanism that is dominated by the C-terminal ISG15 domain. This study fundamentally improves our understanding of the SARS-CoV-2 deISGylation complex that will help guide development of COVID-19 therapeutics targeting this complex.


Subject(s)
Coronavirus Papain-Like Proteases/chemistry , Coronavirus Papain-Like Proteases/metabolism , Cytokines/chemistry , Cytokines/metabolism , Interferons/metabolism , SARS-CoV-2/metabolism , Ubiquitins/chemistry , Ubiquitins/metabolism , Coronavirus Papain-Like Proteases/genetics , Cytokines/genetics , Humans , Neutron Diffraction , Protein Conformation , SARS-CoV-2/enzymology , SARS-CoV-2/genetics , Scattering, Small Angle , Ubiquitins/genetics , X-Ray Diffraction
12.
Front Neurorobot ; 15: 751282, 2021.
Article in English | MEDLINE | ID: mdl-35140597

ABSTRACT

This study presents a new approach for an sEMG hand prosthesis based on a 3D printed model with a fully embedded computer vision (CV) system in a hybrid version. A modified 5-layer Smaller Visual Geometry Group (VGG) convolutional neural network (CNN), running on a Raspberry Pi 3 microcomputer connected to a webcam, recognizes the shape of daily use objects, and defines the pattern of the prosthetic grasp/gesture among five classes: Palmar Neutral, Palmar Pronated, Tripod Pinch, Key Grasp, and Index Finger Extension. Using the Myoware board and a finite state machine, the user's intention, depicted by a myoelectric signal, starts the process, photographing the object, proceeding to the grasp/gesture classification, and commands the prosthetic motors to execute the movements. Keras software was used as an application programming interface and TensorFlow as numerical computing software. The proposed system obtained 99% accuracy, 97% sensitivity, and 99% specificity, showing that the CV system is a promising technology to assist the definition of the grasp pattern in prosthetic devices.

13.
Photochem Photobiol ; 97(1): 32-39, 2021 01.
Article in English | MEDLINE | ID: mdl-33174219

ABSTRACT

In this work, the effect of the calcination temperature on the TiO2 synthesis using Pechini's method was reported. The adopted calcination temperatures were 500, 600, and 700°C. XRD measurements indicated the composition of crystalline phases, and from there, the conversion of the anatase phase to rutile. TiO2 Evonik® was used as a reference standard and sodium diclofenac as a standard for photodegradation assessment. The average crystalline size increased. In both cases, this trend accompanied the increase in calcination temperature. The optical properties were performed using diffuse UV-Vis reflectance. Results obtained indicated maximum absorption wavelength values more intense and displaced to the visible region. Also, the estimated band gap energy values decreased. The photocatalytic performance of TiO2 samples was superior to the reference catalyst (TiO2 Evonik® ). Especially in the first 10 minutes, the comparative photodegradation was up to approximately 58% higher. The photodegradation kinetic constants were also higher, and by comparison, up to approximately 73% higher. Toxicity measurements, using Artemias salina, also indicated similar decay behavior in the first 10 minutes, with a performance of up to approximately 60%.


Subject(s)
Diclofenac/chemistry , Titanium/chemistry , Animals , Artemia , Biological Assay , Catalysis , Photolysis , Temperature , X-Ray Diffraction
14.
Animals (Basel) ; 10(12)2020 Dec 10.
Article in English | MEDLINE | ID: mdl-33321976

ABSTRACT

This study was conducted to investigate the effects of dietary supplementation of porcine digestible peptides (PDP), spray-dried plasma (SDP), or a combination of both, on growth performance and the expression of genes related to intestinal function of weaned pigs. A total of 180 piglets (trial 1) and 198 piglets (trial 2) were used to evaluate the partial substitution of soybean ingredients with 2% SDP or 2% PDP (trial 1), and with 3% SDP or the combination of 1% SDP and 2% PDP (SDP-PDP; trial 2) during the pre-starter period (0-14 days). The gene expression of 56 genes was quantified in a qPCR platform in jejunum and ileum samples obtained from piglets 14 d after weaning (trial 2). Piglets fed SDP, PDP and SDP-PDP had a higher body weight (BW), average daily gain (ADG) and feed efficiency (G:F) than the soybean control on day 14 (p < 0.05). In addition, the combination of SDP and PDP upregulated ten genes in jejunum samples (p < 0.05) related to intestinal function. More research is needed to confirm that gene expression upregulation by PDP in combination with SDP has an impact on intestinal function and to elucidate its underlying mechanisms.

15.
Mar Pollut Bull ; 153: 110959, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32275522

ABSTRACT

This study aims to identify, classify, quantify the ingested microplastic by marine teleost fish, in order to analyze the relationship between microplastic and trophic guilds. Food items of 214 individuals of Opisthonema oglinum, Bagre marinus, Cathorops spixii, Sciades herzbergii, Chloroscombrus chrysurus, Conodon nobilis, Haemulopsis corvinaeformis were analyzed. The species were classified according to their trophic guilds (zoobenthivorous or opportunistic/omnivorous). All species ingested microplastic and contamination occurred independently of the trophic guild. Of the sampled fish, 55% were contaminated by microplastic. The most consumed categories were blue (28%) and transparent filaments (20%). Raman spectroscopy measurements detected that most sampled filament corresponds to blue synthetic fiber (polyester). This study can contribute by filling gaps in knowledge regarding sandy beach impacts, which are environments so highly threatened by human activities around the world and are neglected in terms of use and conservation plans.


Subject(s)
Environmental Monitoring , Fishes , Microplastics , Water Pollutants, Chemical , Animals , Brazil , Eating , Feeding Behavior , Gastrointestinal Contents , Plastics
16.
J Biomech ; 95: 109279, 2019 Oct 11.
Article in English | MEDLINE | ID: mdl-31443944

ABSTRACT

Computational models of the human brain are widely used in the evaluation and development of helmets and other protective equipment. These models are often attempted to be validated using cadaver tissue displacements despite studies showing neural tissue degrades quickly after death. Addressing this limitation, this study aimed to develop a technique for quantifying living brain motion in vivo using a closed head impact animal model of traumatic brain injury (TBI) called CHIMERA. We implanted radiopaque markers within the brain of three adult ferrets and resealed the skull while the animals were anesthetized. We affixed additional markers to the skull to track skull kinematics. The CHIMERA device delivered controlled, repeatable head impacts to the head of the animals while the impacts were fluoroscopically stereo-visualized. We observed that 1.5 mm stainless steel fiducials (∼8 times the density of the brain) migrated from their implanted positions while neutral density targets remained in their implanted position post-impact. Brain motion relative to the skull was quantified in neutral density target tests and showed increasing relative motion at higher head impact severities. We observed the motion of the brain lagged behind that of the skull, similar to previous studies. This technique can be used to obtain a comprehensive dataset of in vivo brain motion to validate computational models reflecting the mechanical properties of the living brain. The technique would also allow the mechanical response of in vivo brain tissue to be compared to cadaveric preparations for investigating the fidelity of current human computational brain models.


Subject(s)
Brain Injuries, Traumatic/physiopathology , Brain/physiopathology , Head/physiopathology , Motion , Animals , Biomechanical Phenomena , Computer Simulation , Disease Models, Animal , Ferrets , Head Protective Devices , Humans , Image Processing, Computer-Assisted , Radiostereometric Analysis , Skull
17.
PLoS One ; 14(4): e0214601, 2019.
Article in English | MEDLINE | ID: mdl-30998678

ABSTRACT

RecA is a multifunctional protein that plays a central role in DNA repair in bacteria. The structural Make ATP Work motif (MAW) is proposed to control the ATPase activity of RecA. In the present work, we report the biochemical activity and structural effects of the L53Q mutation at the MAW motif of the RecA protein from H. seropedicae (HsRecA L53Q). In vitro studies showed that HsRecA L53Q can bind ADP, ATP, and ssDNA, as does wild-type RecA. However, the ATPase and DNA-strand exchange activities were completely lost. In vivo studies showed that the expression of HsRecA L53Q in E. coli recA1 does not change its phenotype when cells were challenged with MMS and UV. Molecular dynamics simulations showed the L53Q point mutation did not cause large conformational changes in the HsRecA structure. However, there is a difference on dynamical cross-correlation movements of the residues involved in contacts within the ATP binding site and regions that hold the DNA binding sites. Additionally, a new hydrogen bond, formed between Q53 and T49, was hypothesized to allow an independent motion of the MAW motif from the hydrophobic core, what could explain the observed loss of activity of HsRecA L53Q.


Subject(s)
Adenosine Triphosphate/metabolism , DNA Repair , Herbaspirillum/genetics , Rec A Recombinases/genetics , Adenosine Triphosphatases/metabolism , Amino Acid Motifs , Binding Sites , DNA, Single-Stranded/metabolism , Escherichia coli/metabolism , Escherichia coli/radiation effects , Hydrolysis , Molecular Dynamics Simulation , Point Mutation , Protein Binding , Protein Structure, Tertiary , Rec A Recombinases/chemistry , Rec A Recombinases/metabolism , Ultraviolet Rays
18.
Sci Rep ; 8(1): 7677, 2018 05 16.
Article in English | MEDLINE | ID: mdl-29769541

ABSTRACT

Traumatic brain injury is a major source of global disability and mortality. Preclinical TBI models are a crucial component of therapeutic investigation. We report a tunable, monitored model of murine non-surgical, diffuse closed-head injury-modCHIMERA-characterized by impact as well as linear and rotational acceleration. modCHIMERA is based on the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) platform. We tested this model at 2 energy levels: 1.7 and 2.1 Joules-substantially higher than previously reported for this system. Kinematic analysis demonstrated linear acceleration exceeding injury thresholds in humans, although outcome metrics tracked impact energy more closely than kinematic parameters. Acute severity metrics were consistent with a complicated-mild or moderate TBI, a clinical population characterized by high morbidity but potentially reversible pathology. Axonal injury was multifocal and bilateral, neuronal death was detected in the hippocampus, and microglial neuroinflammation was prominent. Acute functional analysis revealed prolonged post-injury unconsciousness, and decreased spontaneous behavior and stimulated neurological scores. Neurobehavioral deficits were demonstrated in spatial learning/memory and socialization at 1-month. The overall injury profile of modCHIMERA corresponds with the range responsible for a substantial portion of TBI-related disability in humans. modCHIMERA should provide a reliable platform for efficient analysis of TBI pathophysiology and testing of treatment modalities.


Subject(s)
Behavior, Animal , Brain Concussion/complications , Brain Injuries, Traumatic/complications , Disease Models, Animal , Head Injuries, Closed/complications , Microglia/pathology , Nervous System Diseases/etiology , Animals , Biomechanical Phenomena , Brain Concussion/physiopathology , Brain Injuries, Traumatic/physiopathology , Female , Head Injuries, Closed/physiopathology , Male , Maze Learning , Mice , Mice, Inbred C57BL , Motor Activity , Nervous System Diseases/pathology
19.
eNeuro ; 4(5)2017.
Article in English | MEDLINE | ID: mdl-28966972

ABSTRACT

Diffuse axonal injury (DAI) is a hallmark of traumatic brain injury (TBI) pathology. Recently, the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) was developed to generate an experimental model of DAI in a mouse. The characterization of DAI using diffusion tensor magnetic resonance imaging (MRI; diffusion tensor imaging, DTI) may provide a useful set of outcome measures for preclinical and clinical studies. The objective of this study was to identify the complex neurobiological underpinnings of DTI features following DAI using a comprehensive and quantitative evaluation of DTI and histopathology in the CHIMERA mouse model. A consistent neuroanatomical pattern of pathology in specific white matter tracts was identified across ex vivo DTI maps and photomicrographs of histology. These observations were confirmed by voxelwise and regional analysis of DTI maps, demonstrating reduced fractional anisotropy (FA) in distinct regions such as the optic tract. Similar regions were identified by quantitative histology and exhibited axonal damage as well as robust gliosis. Additional analysis using a machine-learning algorithm was performed to identify regions and metrics important for injury classification in a manner free from potential user bias. This analysis found that diffusion metrics were able to identify injured brains almost with the same degree of accuracy as the histology metrics. Good agreement between regions detected as abnormal by histology and MRI was also found. The findings of this work elucidate the complexity of cellular changes that give rise to imaging abnormalities and provide a comprehensive and quantitative evaluation of the relative importance of DTI and histological measures to detect brain injury.


Subject(s)
Diffuse Axonal Injury/diagnostic imaging , Diffuse Axonal Injury/etiology , Diffusion Magnetic Resonance Imaging , Head Injuries, Closed/complications , Acceleration/adverse effects , Amyloid beta-Protein Precursor/metabolism , Animals , Anisotropy , Calcium-Binding Proteins/metabolism , Diffuse Axonal Injury/pathology , Disease Models, Animal , Glial Fibrillary Acidic Protein/metabolism , Head Injuries, Closed/etiology , Image Processing, Computer-Assisted , Male , Mice , Mice, Inbred C57BL , Microfilament Proteins/metabolism , Optic Tract/pathology
20.
Pesqui. vet. bras ; 37(9): 931-936, Sept. 2017. tab, mapas
Article in English | LILACS, VETINDEX | ID: biblio-895523

ABSTRACT

This study focused on assessing the prevalence, geospatial distribution and risk factors for bovine cysticercosis in cattle from the state of Rondônia, Brazil, through the years 2012 to 2015. The prevalence established was 0.014% (95% C.I. 0.013-0.014), with a higher detection of unviable cysticerci (84.80%). The municipalities of Itapuã do Oeste, Candeias do Jamari, Nova Brasilândia D'Oeste, Pimenteiras do Oeste, Porto Velho, Nova Mamoré, Urupá and Guajará-Mirim had higher risk (OR>1; p<0.05) for cysticercosis occurrence compared with the municipality of Castanheiras (OR=1). The Administrative Regions of Porto Velho, Guajará-Mirim, Colorado D'Oeste, Cacoal, Ji-Paraná had higher risk (OR>1; p<0.05) for cysticercosis occurrence in the slaughtered animals than those reared in Ariquemes Administrative Region (OR=1). Some variables such as human population density (OR=2.15; 2.15-2.16), percentage of urban houses with inappropriate sewage system (OR=1.91, 1.91-.1.92) and percentage of inappropriate rural sewage system (OR=1.14, 1.14-1.14) were significantly associated (p<0.05) with the occurrence of bovine cysticercosis. In conclusion, the prevalence of bovine cysticercosis in the state of Rondônia was 0.014% (95% C.I. 0.013-0.014) and higher-risk areas were identified, providing useful information to Official Sanitary Inspection System in order to improve cysticercosis detection. Also, human population density and the lack of appropriate sewage system in urban and rural areas are closely related to bovine cysticercosis occurrence in this state.(AU)


Este estudo objetivou avaliar a prevalência, distribuição espacial e fatores de risco para a ocorrência de cisticercose bovina em animais abatidos oriundos do Estado de Rondônia, Brasil, entre os anos de 2012 a 2015. A prevalência observada foi de 0,014% (I.C. 95% 0,013-0,014), com maior detecção de cisticercos inviáveis (84,80%). Os municípios de Itapuã do Oeste, Candeias do Jamari, Nova Brasilândia D'Oeste, Pimenteiras do Oeste, Porto Velho, Nova Mamoré, Urupá e Guajará-Mirim apresentaram maior risco (OR>1; p<0.05) para a ocorrência da enfermidade quando comparadas ao município de Castanheiras (OR=1). As Regiões Administrativas de Porto Velho, Guajará-Mirim, Colorado D'Oeste, Cacoal, Ji-Paraná, respectivamente, apresentaram maior risco (OR>1; p<0.05) para a ocorrência de cisticercose nos bovinos abatidos comparadas à Região Administrativa de Ariquemes (OR=1). Algumas variáveis como a densidade populacional humana (OR=2,15; 2,15-2,16), percentual de domicílios urbanos com saneamento inadequado (OR=1,91, 1,91-1,92) e percentual de saneamento rural inadequado (OR=1,14, 1,14-1,14) apresentaram-se como fatores de risco significativos (p<0.05) para a ocorrência de cisticercose bovina. Conclui-se que a prevalência de cisticercose bovina no Estado de Rondônia foi 0,014% (I.C. 95% 0,013-0,014) e que áreas de maior ocorrência puderam ser identificadas, fornecendo informações a serem utilizadas pelo Serviço de Inspeção Federal para melhorar a detecção dos casos. Ainda, a densidade da população humana e a deficiência de sistemas de tratamento de esgotos urbanos e rurais estão intimamente relacionadas com a ocorrência da cisticercose bovina neste estado.(AU)


Subject(s)
Animals , Cattle , Cysticercosis/epidemiology , Disease Outbreaks/veterinary , Taenia saginata , Brazil , Zoonoses , Risk Factors , Geographic Information Systems
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