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The glymphatic system, a macroscopic waste clearance system in the brain, is crucial for maintaining neural health. It facilitates the exchange of cerebrospinal and interstitial fluid, aiding the clearance of soluble proteins and metabolites and distributing essential nutrients and signaling molecules. Emerging evidence suggests a link between glymphatic dysfunction and the pathogenesis of neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s disease. These disorders are characterized by the accumulation and propagation of misfolded or mutant proteins, a process in which the glymphatic system is likely involved. Impaired glymphatic clearance could lead to the buildup of these toxic proteins, contributing to neurodegeneration. Understanding the glymphatic system’s role in these disorders could provide insights into their pathophysiology and pave the way for new therapeutic strategies. Pharmacological enhancement of glymphatic clearance could reduce the burden of toxic proteins and slow disease progression. Neuroimaging techniques, particularly MRI-based methods, have emerged as promising tools for studying the glymphatic system in vivo. These techniques allow for the visualization of glymphatic flow, providing insights into its function under healthy and pathological conditions. This narrative review highlights current MRI-based methodologies, such as motion-sensitizing pulsed field gradient (PFG) based methods, as well as dynamic gadolinium-based and glucose-enhanced methodologies currently used in the study of neurodegenerative disorders.

Purpose: To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects.Methods: The dependence of CBF on anesthesia dose and time was investigated by simultaneously measuring respiration rate (RR) and heart rate (HR) under four different anesthetic regimens. Quantitative CBF was measured by a phase-contrast (PC) MRI technique. RR was evaluated with a mouse monitoring system (MouseOX) while HR was determined using an ultrashort-TE MRI sequence. CBF, RR, and HR were recorded dynamically with a temporal resolution of 1 min in a total of 19 mice. Linear regression models were used to investigate the relationships among CBF, anesthesia dose, RR, and HR.Results: CBF, RR, and HR all showed a significant dependence on anesthesia dose (p < 0.0001). However, the dose in itself was insufficient to account for the variations in physiological parameters, in that they showed a time-dependent change even for a constant dose. RR and HR together can explain 52.6% of the variations in CBF measurements, which is greater than the amount of variance explained by anesthesia dose (32.4%). Based on the multi-parametric regression results, a model was proposed to correct the anesthesia effects in mouse CBF measurements, specifically CBFcorrected=CBF+0.58RR−0.41HR−32.66Dose. We also reported awake-state CBF in mice to be 142.0 ± 8.8 mL/100 g/min, which is consistent with the model-predicted value.Conclusion: The accuracy of CBF measurement in mice can be improved by using a correction model that accounts for respiration rate, heart rate, and anesthesia dose.

Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, in vivo tools to assess BBB permeability are scarce and often require the use of exogenous contrast agents. In this study, we aimed to develop a non-contrast arterial-spin-labeling (ASL) based MRI technique to estimate BBB permeability to water in mice. By determining the relative fraction of labeled water spins that were exchanged into the brain tissue as opposed to those that remained in the cerebral veins, we estimated indices of global BBB permeability to water including water extraction fraction (E) and permeability surface-area product (PS). First, using multiple post-labeling delay ASL experiments, we estimated the bolus arrival time (BAT) of the labeled spins to reach the great vein of Galen (VG) to be 691.2 ± 14.5 ms (N = 5). Next, we investigated the dependence of the VG ASL signal on labeling duration and identified an optimal imaging protocol with a labeling duration of 1200 ms and a PLD of 100 ms. Quantitative E and PS values in wild-type mice were found to be 59.9 ± 3.2% and 260.9 ± 18.9 ml/100 g/min, respectively. In contrast, mice with Huntington's disease (HD) revealed a significantly higher E (69.7 ± 2.4%, P = 0.026) and PS (318.1 ± 17.1 ml/100 g/min, P = 0.040), suggesting BBB breakdown in this mouse model. Reproducibility studies revealed a coefficient-of-variation (CoV) of 4.9 ± 1.7% and 6.1 ± 1.2% for E and PS, respectively. The proposed method may open new avenues for preclinical research on pathophysiological mechanisms of brain diseases and therapeutic trials in animal models.

INTRODUCTION: The blood-brain barrier (BBB) is compromised in multiple central nervous system (CNS) disorders associated with neuroinflammation, including multiple sclerosis (MS). Currently available magnetic resonance imaging (MRI) methods, however, are only able to measure BBB leakage in the lower molecular size range with the use of small molecular tracers, i.e., gadolinium (Gd) agents (

Abstract Background Cell transplantation-based treatments for neurological disease are promising, yet graft rejection remains a major barrier to successful regenerative therapies. Our group and others have shown that long-lasting tolerance of transplanted stem cells can be achieved in the brain with systemic application of monoclonal antibodies blocking co-stimulation signaling. However, it is unknown if subsequent injury and the blood-brain barrier breach could expose the transplanted cells to systemic immune system spurring fulminant rejection and fatal encephalitis. Therefore, we investigated whether delayed traumatic brain injury (TBI) could trigger graft rejection. Methods Glial-restricted precursor cells (GRPs) were intracerebroventricularly transplanted in immunocompetent neonatal mice and co-stimulation blockade (CoB) was applied 0, 2, 4, and 6 days post-grafting. Bioluminescence imaging (BLI) was performed to monitor the grafted cell survival. Mice were subjected to TBI 12 weeks post-transplantation. MRI and open-field test were performed to assess the brain damage and behavioral change, respectively. The animals were decapitated at week 16 post-transplantation, and the brains were harvested. The survival and distribution of grafted cells were verified from brain sections. Hematoxylin and eosin staining (HE) was performed to observe TBI-induced brain legion, and neuroinflammation was evaluated immunohistochemically. Results BLI showed that grafted GRPs were rejected within 4 weeks after transplantation without CoB, while CoB administration resulted in long-term survival of allografts. BLI signal had a steep rise following TBI and subsequently declined but remained higher than the preinjury level. Open-field test showed TBI-induced anxiety for all animals but neither CoB nor GRP transplantation intensified the symptom. HE and MRI demonstrated a reduction in TBI-induced lesion volume in GRP-transplanted mice compared with non-transplanted mice. Brain sections further validated the survival of grafted GRPs and showed more GRPs surrounding the injured tissue. Furthermore, the brains of post-TBI shiverer mice had increased activation of microglia and astrocytes compared to post-TBI wildtype mice, but infiltration of CD45+ leukocytes remained low. Conclusions CoB induces sustained immunological tolerance towards allografted cerebral GRPs which is not disrupted following TBI, and unexpectedly TBI may enhance GRPs engraftment and contribute to post-injury brain tissue repair.

Phosphocreatine plays a vital role in cellular energetic homeostasis, but there are no routine diagnostic tests to noninvasively map the distribution with clinically relevant spatial resolution. Here, the authors develop and validate a noninvasive approach for quantifying and imaging phosphocreatine, without contrast agents, on widely available clinical MRI scanners with artificial neural networks.

Cerebrovascular Reactivity (CVR) provides an assessment of the brain's vascular reserve and has been postulated to be a sensitive marker in cerebrovascular diseases. MRI-based CVR measurement typically employs alterations in arterial carbon dioxide (CO2) level while continuously acquiring Blood-Oxygenation-Level-Dependent (BOLD) images. CO2-inhalation and resting-state methods are two commonly used approaches for CVR MRI. However, processing of CVR MRI data often requires special expertise and may become an obstacle in broad utilization of this promising technique. The aim of this work was to develop CVR-MRICloud, a cloud-based CVR processing pipeline, to enable automated processing of CVR MRI data. The CVR-MRICloud consists of several major steps including extraction of end-tidal CO2 (EtCO2) curve from raw CO2 recording, alignment of EtCO2 curve with BOLD time course, computation of CVR value on a whole-brain, regional, and voxel-wise basis. The pipeline also includes standard BOLD image processing steps such as motion correction, registration between functional and anatomic images, and transformation of the CVR images to canonical space. This paper describes these algorithms and demonstrates the performance of the CVR-MRICloud in lifespan healthy subjects and patients with clinical conditions such as stroke, brain tumor, and Moyamoya disease. CVR-MRICloud has potential to be used as a data processing tool for a variety of basic science and clinical applications.

Purpose: Mannitol is a hyperosmolar agent for reducing intracranial pressure and inducing osmotic blood–brain barrier opening (OBBBO). There is a great clinical need for a non-invasive method to optimize the safety of mannitol dosing. The aim of this study was to develop a label-free Chemical Exchange Saturation Transfer (CEST)-based MRI approach for detecting intracranial accumulation of mannitol following OBBBO. Methods: In vitro MRI was conducted to measure the CEST properties of D-mannitol of different concentrations and pH. In vivo MRI and MRS measurements were conducted on Sprague-Dawley rats using a Biospec 11.7T horizontal MRI scanner. Rats were catheterized at the internal carotid artery (ICA) and randomly grouped to receive either 1 mL or 3 mL D-mannitol. CEST MR images were acquired before and at 20 min after the infusion. Results: In vitro MRI showed that mannitol has a strong, broad CEST contrast at around 0.8 ppm with a mM CEST MRI detectability. In vivo studies showed that CEST MRI could effectively detect mannitol in the brain. The low dose mannitol treatment led to OBBBO but no significant mannitol accumulation, whereas the high dose regimen resulted in both OBBBO and mannitol accumulation. The CEST MRI findings were consistent with 1H-MRS and Gd-enhanced MRI assessments. Conclusion: We demonstrated that CEST MRI can be used for non-invasive, label-free detection of mannitol accumulation in the brain following BBBO treatment. This method may be useful as a rapid imaging tool to optimize the dosing of mannitol-based OBBBO and improve its safety and efficacy.

Detecting Alzheimer's disease (AD) at an early stage brings a lot of benefits including disease management and actions to slow the progression of the disease. Here, we demonstrate that reduced creatine chemical exchange saturation transfer (CrCEST) contrast has the potential to serve as a new biomarker for early detection of AD. The results on wild type (WT) mice and two age-matched AD models, namely tauopathy (Tau) and Aβ amyloidosis (APP), indicated that CrCEST contrasts of the cortex and corpus callosum in the APP and Tau mice were significantly reduced compared to WT counterpart at an early stage (6-7 months) (p

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system in which the immune system attacks the myelin and axons, consequently leading to demyelination and axonal injury. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of MS, and currently various types of MRI techniques have been used to detect the pathology of MS based on unique mechanisms. In this study, we applied the relayed nuclear Overhauser effect weighted (rNOEw) imaging to study human MS at clinical 3T. Three groups of subjects, including 20 normal control (NC) subjects, 14 neuromyelitis optica spectrum disorders (NMOSD) patients and 21 MS patients, were examined at a clinical 3T MRI scanner. Whole-brain rNOEw images of each subject were obtained by acquiring a control and a labeled image within four minutes. Significantly lower brain rNOEw contrast was detected in MS group compared to NC (P = 0.008) and NMOSD (P = 0.014) groups, while no significant difference was found between NC and NMOSD groups (P = 0.939). The lower rNOEw contrast of MS group compared to NC/NMOSD group was significant in white matter (P = 0.041/0.021), gray matter (P = 0.004/0.020) and brain parenchyma (P = 0.015/0.021). Moreover, MS lesions showed higher number and larger size but lower rNOEw contrast than NMOSD lesions (P = 0.002). Our proposed rNOEw imaging scheme has potential to serve as a new method for assisting MS diagnosis. Importantly, it may be used to identify MS from NMOSD.

Background: Characterization of physiological parameters of the aging brain, such as perfusion and brain metabolism, is important for understanding brain function and diseases. Aging studies on human brain have mostly been based on the cross-sectional design, while the few longitudinal studies used relatively short follow-up time compared to the lifespan.Objectives: To determine the longitudinal time courses of cerebral physiological parameters across the adult lifespan in mice.Methods: The present work examined longitudinal changes in cerebral blood flow (CBF), cerebral venous oxygenation (Yv), and cerebral metabolic rate of oxygen (CMRO2) using MRI in healthy C57BL/6 mice from 3 to 20 months of age. Each mouse received 16 imaging sessions at an ~1-month interval.Results: Significant increases with age were observed in CBF (p = 0.017) and CMRO2 (p < 0.001). Meanwhile, Yv revealed a significant decrease (p = 0.002) with a non-linear pattern (p = 0.013). The rate of change was 0.87, 2.26, and −0.24% per month for CBF, CMRO2, and Yv, respectively. On the other hand, systemic parameters such as heart rate did not show a significant age dependence (p = 0.47). No white-matter-hyperintensities (WMH) were observed on the T2-weighted image at any age of the mice.Conclusion: With age, the mouse brain revealed an increase in oxygen consumption. This observation is consistent with previous findings in humans using a cross-sectional design and suggests a degradation of the brain's energy production or utilization machinery. Cerebral perfusion remains relatively intact in aged mice, at least until 20 months of age, consistent with the absence of WMH in mice.

Multiple sclerosis (MS) is an autoimmune disorder that targets myelin proteins and results in extensive damage in the central nervous system in the form of focal lesions as well as diffuse molecular changes. Lesions are currently detected using T1-weighted, T2-weighted, and gadolinium-enhanced magnetic resonance imaging (MRI); however, monitoring such lesions has been shown to be a poor predictor of disease progression. Chemical exchange saturation transfer (CEST) MRI is sensitive to many of the biomolecules in the central nervous system altered in MS that cannot be detected using conventional MRI. We monitored disease progression in an experimental autoimmune encephalomyelitis (EAE) model of MS using on resonance variable delay multiple pulse (onVDMP) CEST MRI. Alterations in onVDMP signal were observed in regions responsible for hindlimb function throughout the central nervous system. Histological analysis revealed glial activation in areas highlighted in onVDMP CEST MRI. onVDMP signal changes in the 3rd ventricle preceded paralysis onset that could not be observed with conventional MRI techniques. Hence, the onVDMP CEST MRI signal has potential as a novel imaging biomarker and predictor of disease progression in MS.

Abstract The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage. However, this assumption has never been experimentally tested. Here we take advantage of the leaky tetracycline promoter system in the Tat-transgenic mouse to show that a chronic very low-level expression of Tat is associated with astrocyte activation, inflammatory cytokine expression, ceramide accumulation, reductions in brain volume, synaptic, and axonal damage that occurs over a time frame of 1 year. These data suggest that a chronic low-level production of Tat may contribute to progressive neurological damage in virally suppressed HIV-infected individuals.

Abstract The incidence of accidental and intentional acid skin burns is rising. Current treatment strategies are mostly inadequate, leaving victims disfigured and without treatment options. Here, we have shown that transplantation of adipose-derived stem cells (ASCs) accelerates the process of acid burn wound-healing. Pre-conditioning of ASCs using ascorbic acid (AA) or hypoxic conditions provided additional benefit. While the wounds were ultimately healed in all mice, histological analysis revealed that, in non-transplanted animals, the number of hair follicles was reduced. Bioluminescent imaging (BLI) of transplanted ASCs revealed a gradual loss of transplanted cells, with a similar rate of cell death for each treatment group. The signal of fluorinated cells detected by a clinically applicable 19F MRI method correlated with the BLI findings, which points to 19F MRI as a reliable method with which to track ASCs after transplantation to skin wounds. No difference in therapeutic effect or cell survival was observed between labeled and non-labeled cells. We conclude that, despite being short-lived, transplanted ASCs can accelerate wound-healing and reduce hair loss in acid-burn skin injury. The fluorine nanoemulsion is a clinically applicable cell label capable of reporting on the survival of transplanted cells.

The glymphatic system, a macroscopic waste clearance system in the brain, is crucial for maintaining neural health. It facilitates the exchange of cerebrospinal and interstitial fluid, aiding the clearance of soluble proteins and metabolites and distributing essential nutrients and signaling molecules. Emerging evidence suggests a link between glymphatic dysfunction and the pathogenesis of neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s disease. These disorders are characterized by the accumulation and propagation of misfolded or mutant proteins, a process in which the glymphatic system is likely involved. Impaired glymphatic clearance could lead to the buildup of these toxic proteins, contributing to neurodegeneration. Understanding the glymphatic system’s role in these disorders could provide insights into their pathophysiology and pave the way for new therapeutic strategies. Pharmacological enhancement of glymphatic clearance could reduce the burden of toxic proteins and slow disease progression. Neuroimaging techniques, particularly MRI-based methods, have emerged as promising tools for studying the glymphatic system in vivo. These techniques allow for the visualization of glymphatic flow, providing insights into its function under healthy and pathological conditions. This narrative review highlights current MRI-based methodologies, such as motion-sensitizing pulsed field gradient (PFG) based methods, as well as dynamic gadolinium-based and glucose-enhanced methodologies currently used in the study of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

We report time-resolved angle-resolved photoemission study on Ta2Ni1-xCoxSe5 (x = 0.10) in which the excitonic insulator (EI) transition temperature is reduced by Co substitution for Ni. In the photoinduced phase, the conduction band is clearly observed and the energy gap between the conduction and valence bands is undetectably small within the energy resolution. Assuming that the energy gap is closed, the conduction band crosses or overlaps with the valence band near the Fermi level resembling a nodal semimetal. [ABSTRACT FROM AUTHOR]

Glycogen plays a central role in glucose homeostasis and is abundant in several types of tissue. We report an MRI method for imaging glycogen noninvasively with enhanced detection sensitivity and high specificity, using the magnetic coupling between glycogen and water protons through the nuclear Overhauser enhancement (NOE). We show in vitro that the glycogen NOE (glycoNOE) signal is correlated linearly with glycogen concentration, while pH and temperature have little effect on its intensity. For validation, we imaged glycoNOE signal changes in mouse liver, both before and after fasting and during glucagon infusion. The glycoNOE signal was reduced by 88 ± 16% (n = 5) after 24 h of fasting and by 76 ± 22% (n = 5) at 1 h after intraperitoneal (i.p.) injection of glucagon, which is known to rapidly deplete hepatic glycogen. The ability to noninvasively image glycogen should allow assessment of diseases in which glucose metabolism or storage is altered, for instance, diabetes, cardiac disease, muscular disorders, cancer, and glycogen storage diseases. [ABSTRACT FROM AUTHOR]

A new type of spin diffusion, cross-relaxation driven spin diffusion (CRDSD), is investigated using 15N NMR on a N-acetyl-L-valyl-L-leucine (NAVL) single crystal under stationary condition. A two-dimensional (2D) pulse sequence that correlates the chemical shifts of 15N nuclei, with a radio-frequency spin lock on the 15N channel during the mixing time, is used to observe CRDSD. Experimental results obtained using CRDSD, rf-driven spin diffusion, and proton driven spin diffusion approaches on the NAVL single crystal are compared. Our experimental results suggest that the 15N spin diffusion rate can be enhanced by about 1000 times using CRDSD than by the normal proton driven spin diffusion. Interestingly, the required spin-locking rf field strength for CRDSD is much lower than that used for the rf-driven spin diffusion experiments. The cross-peak patterns observed in 2D 15N–15N correlation spectra using CRDSD and RFDSD are very different as they arise from different spin-spin interactions. A detailed theory describing CRDSD and RFDSD processes is also presented using a thermodynamic model. The speedy spin diffusion process rendered by the CRDSD approach will be useful to assign resonances from a uniformly 15N or 13C labeled proteins and peptides, particularly in aligned samples. [ABSTRACT FROM AUTHOR]

The application of the [43.sup]Ca magic angle spinning solid-state NMR experiments in studying the significance of different compounds in the formation of bone is demonstrated. The calcium environment of the bone is shown to be extremely similar to the carbonated apaptite.

A solid-state NMR method, dipolar enhanced polarization transfer (DREPT), is described that has helped in determining the side-chain dynamics from membrane proteins in lipid bilayers. An appropriate model is used for determining the side-chain dynamics and providing additional information on the topology and function of a membrane protein in its native environment.

Two-dimensional proton-evolved local-field (2D PELF) pulse sequences are implemented by using either composite zero cross-polarization (COMPOZER-CP) or windowless isotropic mixing (WIM) for magnetization transfer. The results from magnetically aligned bicelles containing uniformly [super 15]N-labeled cytochrome [b.sub.5] have shown that the PELF-based experimental approaches have a major impact on solid-state NMR spectroscopy of membrane proteins and other membrane-associated molecules in magnetically aligned bicelles.

Solid-state NMR spectroscopy, controlled dehydration and H/D exchange are used for revealing the structural changes of an intact piece of bovine cortical bone. The results have shown that glycosaminoglycans in the collagen fiber and mineral interface have chelated with a [Ca.sup.2+] ion present on the surface of the mineral through sulfate or carboxylate groups.

The structures of the human and rat islet amyloid polypeptide ([IAPP.sub.1-19]) peptides in dodecylphosphocholine (DPC) micelles are examined. The difference in peptide topology in the membrane has corresponded to similar topology differences for the full-length human rat IAPP peptides, with the toxic human IAPP peptide adopting a transmembrane orientation and the nontoxic rat IAPP peptide bound to the surface of the membrane.

Sepsis-induced acute kidney injury (SAKI) is a major complication of kidney disease associated with increased mortality and faster progression. Therefore, the development of imaging biomarkers to detect septic AKI is of great clinical interest. In this study, we aimed to characterize the endogenous chemical exchange saturation transfer (CEST) MRI contrast in the lipopolysaccharide (LPS)-induced SAKI mouse model and to investigate the use of CEST MRI for detecting such injury. We used a SAKI mouse model that was generated by i.p. injection of 10 mg/kg LPS. The resulting kidney injury was confirmed by the elevation of serum creatinine and histology. MRI assessments were performed 24 h after LPS injection, including CEST MRI at different B1 strengths (1, 1.8 and 3 µT), T1 mapping, T2 mapping and conventional magnetization transfer contrast (MTC) MRI. The CEST MRI results were analyzed using Z-spectra, in which the normalized water signal saturation (Ssat/S0) is measured as a function of saturation frequency. Substantial decreases in CEST contrast were observed at both 3.5 and - 3.5 ppm frequency offset from water at all B1 powers, with the most significant difference obtained at a B1 of 1.8 µT. The average Ssat/S0 differences between injured and normal kidneys were 0.07 (0.55 ± 0.04 versus 0.62 ± 0.04, P = 0.0028) and 0.07 (0.50 ± 0.04 versus 0.57 ± 0.03, P = 0.0008) for 3.5 and - 3.5 ppm, respectively. In contrast, the T1 and T2 relaxation times and MTC contrast in the injured kidneys did not show a significant change compared with the normal control. Our results showed that CEST MRI is more sensitive to the pathological changes in injured kidneys than the changes in T1, T2 and MTC effect, indicating its potential clinical utility for molecular imaging of renal diseases. [ABSTRACT FROM AUTHOR]

Stem cell therapy for neurological disorders reached a pivotal point when the efficacy of several cell types was demonstrated in small animal models. Translation of stem cell therapy is contingent upon overcoming the challenge of effective cell delivery to the human brain, which has a volume ~1000 times larger than that of the mouse. Intra-arterial injection can achieve a broad, global, but also on-demand spatially targeted biodistribution; however, its utility has been limited by unpredictable cell destination and homing as dictated by the vascular territory, as well as by safety concerns. We show here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus be used to accurately predict the distribution of intra-arterial administered stem cells. Moreover, high-speed MRI enables the real-time visualization of cell homing, providing the opportunity for immediate intervention in the case of undesired biodistribution. [ABSTRACT FROM AUTHOR]

A two-step heteronuclear enhancement approach was combined with chemical exchange saturation transfer (CEST) to magnify 15N MRI signal of molecules through indirect detection via water protons. Previous CEST studies have been limited to radiofrequency (rf) saturation transfer or excitation transfer employing protons. Here, the signal of 15N is detected indirectly through the water signal by first inverting selectively protons that are scalar-coupled to 15N in the urea molecule, followed by chemical exchange of the amide proton to bulk water. In addition to providing a small sensitivity enhancement, this approach can be used to monitor the exchange rates and thus the pH sensitivity of the participating 15N-bound protons. [ABSTRACT FROM AUTHOR]

A pair of spot-focusing horn lens antenna is the key component in a free-space measurement system. The electromagnetic constitutive parameters of a planar sample are determined using transmitted and reflected electromagnetic beams. These parameters are obtained from the measured scattering parameters by the microwave network analyzer, thickness of the sample, and wavelength of a focused beam on the sample. Free-space techniques introduced by most papers consider the focused wavelength as the free-space wavelength. But in fact, the incident wave projected by a lens into the sample approximates a Gaussian beam, thus, there has an elongation of the wavelength in the focused beam and this elongation should be taken into consideration in dielectric and magnetic measurement. In this paper, elongation of the wavelength has been analyzed and measured. Measurement results show that the focused wavelength in the vicinity of the focus has an elongation of 1%-5% relative to the free-space wavelength. Elongation's influence on the measurement result of the permittivity and permeability has been investigated. Numerical analyses show that the elongation of the focused wavelength can cause the increase of the measured value of the permeability relative to traditionally measured value, but for the permittivity, it is affected by several parameters and may increase or decrease relative to traditionally measured value. [ABSTRACT FROM AUTHOR]

Microsomal monoxygenase enzymes of the cytochrome-P450 family are found in all biological kingdoms, and play a central role in the breakdown of metabolic as well as xenobiotic, toxic and 70% of the drugs in clinical use. Full-length cytochrome-b5 has been shown to be important for the catalytic activity of cytochrome-P450. Despite the significance in understanding the interactions between these two membrane-associated proteins, only limited high-resolution structural information on the full-length cytochrome-P450 and the cytochromes-b5-P450 complex is available. Here, we report a structural study on a functional ∼72-kDa cytochromes-b5-P450 complex embedded in magnetically-aligned bicelles without having to freeze the sample. Functional and solid-state NMR (Nuclear Magnetic Resonance) data reveal interactions between the proteins in fluid lamellar phase bilayers. In addition, our data infer that the backbone structure and geometry of the transmembrane domain of cytochrome-b5 is not significantly altered due to its interaction with cytochrome-P450, whereas the mobility of cytochrome-b5 is considerably reduced. [ABSTRACT FROM AUTHOR]

In this paper, the difficulty in orienting the B2phase of the banana mesogen 1,3-Phenylene-bis 4-4-(10-undecenyloxy)-benzoyloxy benzoate (Pbis11BB) in a relatively high magnetic field is reported based on some observations using both 13C and 2H NMR. 2H NMR spectra recorded for the two labeled isotopomers of Pbis11BB in the isotropic and B2phases are shown here. Preliminary results on the deuteron spin−spin relaxation (T2) data are reported at 61 MHz in order to underline the peculiar slow dynamics of banana-shaped liquid crystals (BLC), and these results are discussed in the framework of recent studies on similar BLC. The molecular structure and dynamics in the B2and crystalline phases are also studied by 13C solid-state NMR techniques. The results also point to the slow dynamics in the B2phase of Pbis11BB. In particular, two-dimensional MAS exchange experiment has been performed to shed light on the molecular conformation structure of the five-ring banana core in the crystalline phase of Pbis11BB, and to compare with that of quantum mechanical calculations reported in the literature. [ABSTRACT FROM AUTHOR]

A deuterium two-dimensional exchange NMR technique is used to study the chiral smectic C (SmC*) and chiral subphases (Sm%@mt;sys@%%@ital@%C%@rsf@%%@sx@%Fi1%@be@%*%@sxx@%%@mx@%, Sm%@mt;sys@%%@ital@%C%@rsf@%%@sx@%Fi2%@be@%*%@sxx@%%@mx@%) of a smectogen (s)-1-methylheptyl 4‘-(4-n-decyloxy-benzoyloxy)biphenyl-4-carboxylate (10B1M7). The aim is to demonstrate how this technique can be combined with sample rotation in the magnetic field to obtain the fast translational self-diffusion constant along the helical pitch in the SmC* phase and to shed light on the structure of helicoidal superlattice in the three-layer Sm%@mt;sys@%%@ital@%C%@rsf@%%@sx@%Fi1%@be@%*%@sxx@%%@mx@% and four-layer Sm%@mt;sys@%%@ital@%C%@rsf@%%@sx@%Fi2%@be@%*%@sxx@%%@mx@% phases. The cross-peak intensities in the 2D exchange spectrum are sensitive to the disposition of molecules in the three- and four-layer base unit. The results support the “asymmetric Clock model” as an appropriate description of the ferrielectric phases in this compound. [ABSTRACT FROM AUTHOR]

The article presents a study which uses copper-chelated lipid in enhancing nuclear magnetic resonance (NMR) experiment sensitivity on lipid bilayers to address the limitations posed by for high-throughput application of solid-state NMR spectroscopy. It mentions that the study carried its objective under aligned static and unaligned magic-angle spinning (MAS) conditions. The results suggest that the present study will impact studies that cater on membrane-associated peptides and proteins.

针对市场在售的调和油、玉米油、大豆油、花生油和菜籽油等食用植物油,随机购买20种共290份食用植物油样品。采用液相色谱法测定AFB1、AFB2、AFG1、AFG2以及OTA、OTB真菌毒素的含量，对食用植物油中黄曲霉毒素和赭曲霉毒素的污染水平和分布特征进行分析。结果表明：20种290份食用植物油样品中，有16种共67份样品存在不同程度的真菌毒素污染，总污染率达到23.1%，不同种类食用植物油污染呈现“多种类、共分布”的特点，其中AFG1污染率（14.8%）最高，其次为OTA（13.4%）。绝大多数阳性样本受1～4种真菌毒素污染，仅有少数阳性样本受真菌毒素污染数量达到5种。总体上食用植物油样品受到多种真菌毒素的混合污染情况比较严重，应引起一定的重视。 A total of 290 samples from 20 kinds of edible vegetable oils such as blended oil, corn oil, soybean oil, peanut oil, and rapeseed oil on the market were randomly purchased. Then, the contents of AFB1, AFB2, AFG1, AFG2, OTA and OTB were accurately determined by HPLC to investigate the pollution levels and distribution characteristics of aflatoxins and ochratoxins in edible vegetable oils. The results showed that among the 20 kinds of 290 edible vegetable oil samples, 16 kinds of 67 samples suffered from different degrees of mycotoxin contamination, and the total pollution rate reached 23.1%. The pollution of different kinds of edible vegetable oils presented the characteristics of multi-species and co-distribution. AFG1 had the highest pollution rate (14.8%), followed by OTA (13.4%). Besides, the vast majority of positive samples were contaminated by 1-4 kinds of mycotoxins, only a few positive samples were contaminated with 5 kinds of mycotoxins. Overall, the problem that the edible vegetable oil samples are polluted by multiple mycotoxins is serious and should be paid attention to.

Islet amyloid polypeptide (IAPP or amylin) is a 37-residue peptide hormone associated with glucose metabolism that is cosecreted with insulin by β-cells in the pancreas. Since human IAPP is a highly amyloidogenic peptide, it has been suggested that the formation of APP amyloid fibers is responsible for the death of β-cells during the early stages of type II diabetes. It has been hypothesized that transient membrane-bound α-helical structures of human IAPP are. precursors to the formation of these amyloid deposits. On the other hand, rat IAPP forms transient α-helical structures but does not progress further to form amyloid fibrils. To understand the nature of this intermediate state and the difference in toxicity between the rat and human versions of IAPP, we have solved the high-resolution structure of rat IAPP in the membrane-mimicking detergent micelles composed of dodecylphosphocholine. The structure is characterized by a helical region spanning the residues A5 to S23 and a disordered C-terminus. A distortion in the helix is seen at R18 and S19 that may be involved in receptor binding. Paramagnetic quenching NMR experiments indicate that rat APP is bound on the surface of the micelle, in agreement with other nontoxic forms of APP. A comparison to the detergent-bound structures of other APP variants indicates that the N-terminal region may play a crucial role in the self-association and toxicity of IAPP by controlling access to the putative dimerization interface on the hydrophobic face of the amphipathic helix. [ABSTRACT FROM AUTHOR]

The article offers information on the Altered cerebral glucose in brain parenchyma and cerebrospinal fluid of early Alzheimer's disease detected by dynamic glucose-enhanced magnetic resonance imaging (MRI). It discusses the dynamic glucose-enhanced magnetic resonance imaging approach was developed to simultaneously monitor d-glucose uptake and clearance in both brain parenchyma and cerebrospinal fluid.

Enzymes that degrade lignocellulose to simple sugars are of great interest in research and for biotechnology because of their role in converting plant biomass to fuels and chemicals. The synthesis of cellulolytic enzymes in filamentous fungi is tightly regulated at the transcriptional level, with the transcriptional activator ClrB/CLR-2 playing a critical role in many species. In Penicillium oxalicum, clrB overexpression could not relieve the dependence of cellulase expression on cellulose as an inducer, suggesting that clrB is controlled post-transcriptionally. In this study, using a reporter gene system in yeast, we identified the C-terminal region of ClrB/CLR-2 as a transcriptional activation domain. Expression of clrBID, encoding a ClrB derivative in which the DNA-binding and transcriptional activation domains are fused together to remove the middle region, led to cellulase production in the absence of cellulose in P. oxalicum. Strikingly, the clrBID-expressing strain produced cellulase on carbon sources that normally repress cellulase expression, including glucose and glycerol. Results from deletion of the carbon catabolite repressor gene creA in the clrBID-expressing strain suggested that the effect of clrBID is independent of CreA's repressive function. A similar modification of clrB in Aspergillus niger resulted in the production of a mannanase in glucose medium. Taken together, these results indicate that ClrB suppression under noninducing conditions involves its middle region, suggesting a potential strategy to engineer fungal strains for improved cellulase production on commonly used carbon sources. [ABSTRACT FROM AUTHOR]

Microsomal cytochrome b5 (cytb5) is a membrane-bound protein that modulates the catalytic activity of its redox partner, cytochrome P4502B4 (cytP450). Here, we report the first structure of full-length rabbit ferric microsomal cytb5 (16 kDa), incorporated in two different membrane mimetics (detergent micelles and lipid bicelles). Differential line broadening of the cytb5NMRresonances and site-directed mutagenesis data were used to characterize the cytb5 interaction epitope recognized by ferric microsomal cytP450 (56 kDa). Subsequently, a datadriven docking algorithm, HADDOCK (high ambiguity driven biomolecular docking), was used to generate the structure of the complex between cytP4502B4 and cytb5 using experimentally derived restraints from NMR, mutagenesis, and the double mutant cycle data obtained on the full-length proteins. Our docking and experimental results point to the formation of a dynamic electron transfer complex between the acidic convex surface of cytb5 and the concave basic proximal surface of cytP4502B4. The majority of the binding energy for the complex is provided by interactions between residues on the C-helix and β-bulge of cytP450 and residues at the end of helix α4 of cytb5. The structure of the complex allows us to propose an interprotein electron transfer pathway involving the highly conserved Arg-125 on cytP450 serving as a salt bridge between the heme propionates of cytP450 and cytb5. We have also shown that the addition of a substrate to cytP450 likely strengthens the cytb5- cytP450 interaction. This study paves the way to obtaining valuable structural, functional, and dynamic information on membrane- bound complexes. [ABSTRACT FROM AUTHOR]

Poly(amidoamine) (PAMAM) dendrimer nanobiotechnology shows great promise in targeted drug delivery and gene therapy. Because of the involvement of cell membrane lipids with the pharmacological activity of dendrimer nanomedicines, the interactions between dendrimers and lipids are of particular relevance to the pharmaceutical applications of dendrimers. In this study, solid–state NMR was used to obtain a molecular image of the complex of generation–5 (G5) PAMAM dendrimer with the lipid bilayer. Using H radio frequency driven dipolar recoupling (RFDR) and 1H magic angle spinning (MAS) nuclear Overhauser effect spectroscopy (NOESY) techniques, we show that dendrimers are thermodynamically stable when inserted into zwitterionic lipid bilayers. 14N and 31P NMR experiments on static samples and measurements of the mobility of C–H bonds using a 2D proton detected local field protocol under MAS corroborate these results. The localization of dendrimers in the hydrophobic core of lipid bilayers restricts the motion of bilayer lipid tails, with the smaller G5 dendrimer having more of an effect than the larger G7 dendrimer. Fragmentation of the membrane does not occur at low dendrimer concentrations in zwitterionic membranes. Because these results show that the amphipathic dendrimer molecule can be stably incorporated in the interior of the bilayer (as opposed to electrostatic binding at the surface), they are expected to be useful in the design of dendrimer–based nanobiotechnologies. [ABSTRACT FROM AUTHOR]

Nanoscale building blocks are individually exceptionally strong because they are close to ideal, defect-free materials, It is, however, difficult to retain the ideal properties in macroscale composites. Bottom-up assembly of a clay/polymer nanocomposite allowed for the preparation of a homogeneous, optically transparent material with planar orientation of the alumosilicate nanosheets. The stiffness and tensile strength of these multilayer composites are one order of magnitude greater than those of analogous nanocomposites at a processing temperature that is much lower than those of ceramic or polymer materials with similar characteristics. A high level of ordering of the nanoscale building blocks, combined with dense covalent and hydrogen bonding and stiffening of the polymer chains, leads to highly effective load transfer between nanosheets and the polymer. [ABSTRACT FROM AUTHOR]