High-throughput sequencing of single neuron projections reveals spatial organization in the olfactory cortex.

In most sensory modalities, neuronal connectivity reflects behaviorally relevant stimulus features, such as spatial location, orientation, and sound frequency. By contrast, the prevailing view in the olfactory cortex, based on the reconstruction of dozens of neurons, is that connectivity is random. Here, we used high-throughput sequencing-based neuroanatomical techniques to analyze the projections of 5,309 mouse olfactory bulb and 30,433 piriform cortex output neurons at single-cell resolution. Surprisingly, statistical analysis of this much larger dataset revealed that the olfactory cortex connectivity is spatially structured. Single olfactory bulb neurons targeting a particular location along the anterior-posterior axis of piriform cortex also project to matched, functionally distinct, extra-piriform targets. Moreover, single neurons from the targeted piriform locus also project to the same matched extra-piriform targets, forming triadic circuit motifs. Thus, as in other sensory modalities, olfactory information is routed at early stages of processing to functionally diverse targets in a coordinated manner.

Maize auxin response factor ZmARF1 confers multiple abiotic stresses resistances in transgenic Arabidopsis.

Prolonged exposure to abiotic stresses causes oxidative stress, which affects plant development and survival. In this research, the overexpression of ZmARF1 improved tolerance to low Pi, drought and salinity stresses. The transgenic plants manifested tolerance to low Pi by their superior root phenotypic traits: root length, root tips, root surface area, and root volume, compared to wide-type (WT) plants. Moreover, the transgenic plants exhibited higher root and leaf Pi content and upregulated the high affinity Pi transporters PHT1;2 and phosphorus starvation inducing (PSI) genes PHO2 and PHR1 under low Pi conditions. Transgenic Arabidopsis displayed tolerance to drought and salt stress by maintaining higher chlorophyll content and chlorophyll fluorescence, lower water loss rates, and ion leakage, which contributed to the survival of overexpression lines compared to the WT. Transcriptome profiling identified a peroxidase gene, POX, whose transcript was upregulated by these abiotic stresses. Furthermore, we confirmed that ZmARF1 bound to the auxin response element (AuxRE) in the promoter of POX and enhanced its transcription to mediate tolerance to oxidative stress imposed by low Pi, drought and salt stress in the transgenic seedlings. These results demonstrate that ZmARF1 has significant potential for improving the tolerance of crops to multiple abiotic stresses.

Basal metabolic rate and the risk of urolithiasis: a two-sample Mendelian randomization study.

OBJECTIVE: Few studies have investigated the impact of basal metabolic rate (BMR) on the development of urolithiasis, and the causal relationship is yet to be established. In this study, a two-sample Mendelian randomization (MR) analysis was utilized to identify the causal relationship between BMR and risk of urolithiasis. METHOD: Genetic instruments for BMR were drawn from a public genome-wide association study (GWAS). Summary dates on BMR and urolithiasis were obtained from a GWAS meta-analysis with sample sizes of 454,874 and 212,453, respectively. The inverse-variance weighted (IVW) method was provided as the main approach to estimate the causal relationship. The weighted-median method and the MR-Egger method were used as supplements to the IVW method. In addition, we conducted sensitivity analyses, including heterogeneity tests, pleiotropy tests and leave-one-out analysis, to assess the robustness of the outcomes. Furthermore, the funnel plot asymmetry was visually inspected to evaluate possible bias. RESULTS: The inverse-variance weighted data revealed that genetically predicted BMR significantly decreased the risk of urolithiasis [beta coefficient (beta): - 0.2366, odds ratio (OR): 0.7893, 95% confidence interval (CI) 0.6504-0.9579, p = 0.0166]. CONCLUSIONS: BMR has causal effects on urolithiasis in an MR study, and the risk of urolithiasis in patients with lower levels of BMR is higher.

Correlation Between Preoperative and Postoperative Alignment and Kinematic Gait in Total Knee Arthroplasty.

Objective: Maintaining the lower limb in a neutral posture following total knee arthroplasty (TKA) has long been a concept maintained by operators. This study aimed to investigate the relationship between changes in lower limb alignment and the dynamics of knee gait before and after TKA to understand the impact of alignment on gait better and offer a theoretical foundation for correcting lower limb alignment in TKA. Methods: Our study included a group of 20 participants. The cohort consisted of 1 male and 19 females, 11 left and 9 right knees, ages 58 to 81. Using the Opti_Knee® Knee Motion Test System with infrared reflective markers and a high-speed camera, the step length and 6 degrees of freedom of the knee were recorded. Following that, we investigated the association between HKA angle and knee kinematic gait before and after surgery. Results: For preoperative HKA angles ranging from -28° to -3°, we observed increased step length, flexion-extension rotation, and varus-valgus rotation with an increase in HKA angle. Conversely, an increase in HKA angle from -3 ° to 15° corresponded with decreased step length, flexion-extension rotation, and varus-valgus rotation. An increase in HKA angle from 1° to 3° postoperatively increased step length, flexion-extension rotation, and varus-valgus rotation. In contrast, increasing the HKA angle from 3° to 5° resulted in less flexion-extension rotation. The flexion-extension rotation was at its maximum when the HKA angle was 3°. A 3° postoperative varus resulted in improved kinematic gait. Step length, varus-valgus rotation, and flexion-extension rotation increased with increasing HKA angle in the neutral alignment group. In contrast, the non-neutral alignment group exhibited decreased flexion-extension rotation as the HKA angle increased, while step length and varus-valgus rotation increased as the HKA angle increased. The varus-valgus rotation was statistically significant (P < .05) in the preoperative versus early postoperative period in the 6 degrees of freedom. Conclusions: A 3° varus alignment was found to have a superior postoperative knee kinematic gait, implying that a 3° varus alignment may be more suitable as a new gold standard for TKA than the traditional "0°" alignment. The neutral alignment group demonstrated a better knee kinematic gait than the non-neutral alignment group. During early postoperative walking, significant improvements in varus-valgus rotation were found in the 6 degrees of knee freedom.

Characteristic CT angiography findings and clinical value of catheter-related central venous thrombosis in hemodialysis patients with end-stage renal disease.

BACKGROUND: Central catheter-related thrombosis (CRT) is the most common catheter-related complication in patients with end-stage renal disease (ESRD) but is often underappreciated and misdiagnosed by radiologist. PURPOSE: To find the computed tomography angiography (CTA) characteristics of central CRT, then raise the diagnosis of this disorder. MATERIAL AND METHODS: A total of 301 eligible patients with ESRD who experienced both chest multi-phase multidetector CTA (MDCTA) and digital subtraction angiography were enrolled in the final analysis. The location, shape, and related signs of the central CRT in MDCTA images were evaluated. Independent-samples T test, chi-square test, and binary logistic regression were analyzed using SPSS software. RESULTS: In total, 166 patients were found to have CRT using MDCTA, and this was verified by DSA. Central CRT was usually irregular in the superior vena cava segment, and the angle of the contact area between central CRT and catheter was <180° (all P < 0.05). Age, collateral circulation, and venous stenosis were shown to have significant differences when compared to patients without CRT (all P < 0.05), but there were no significant differences about the sex or catheter insertion site. In addition, age and collateral circulation were the factors found to be significantly associated with thrombosis (P < 0.05). In particular, the thrombosis was 2.213 times more likely to be found in those patients with collateral circulation (odds ratio = 2.213, 95% confidence interval = 1.236-3.961). CONCLUSION: Chest multi-phase MDCTA can effectively reduce the missed diagnosis and misdiagnosis of central CRT. It is worth paying more attention to the central CRT especially when the collateral circulation is observed.

Compact MR-compatible ergometer and its application in cardiac MR under exercise stress: A preliminary study.

PURPOSE: To develop a compact MR-compatible ergometer for exercise stress and to initially evaluate the reproducibility of myocardial native T1 and myocardial blood flow (MBF) measurements during exercise stress performed on this ergometer. METHODS: The compact ergometer consists of exercise, workload, and data processing components. The exercise stress can be achieved by pedaling on a pair of cylinders at a predefined frequency with adjustable resistances. Ten healthy subjects were recruited to perform cardiac MRI scans twice in a 3.0T MR scanner, at different days to assess reproducibility. Myocardial native T1 and MBF were acquired at rest and during a moderate exercise. The reproducibility of the two tests was determined by the intra-group correlation coefficient (ICC) and coefficient of variation (CoV). RESULTS: The mean exercise intensity in this pilot study was 45 Watts (W), with an exercise duration of 5 min. Stress induced a significant increase in systolic blood pressure (from 113 ± 11 mmHg to 141 ± 12, P < 0.05) and maximal increase in heart rate by 74 ± 19%. The rate pressure product increased two-fold (P < 0.001). Excellent reproducibility was demonstrated in native T1 during the exercise (CoV = 3.0%), whereas the reproducibility of MBF and myocardial perfusion reserve during the exercise was also good (CoV = 10.7% and 8.8%, respectively). CONCLUSION: This pilot study demonstrated that it is possible to acquire reproducible measurements of myocardial native T1 and MBF during the exercise stress in healthy volunteers using our new compact ergometer.

Low-dose dobutamine cardiovascular magnetic resonance segmental strain study of early phase of intramyocardial hemorrhage rats.

BACKGROUND: This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking. METHODS: Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)-cine sequence. Another FISP-cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and NMI segments were acquired. The efficiency of PRS and PCS (EPRS and EPCS, respectively) were calculated on the basis of the time of every single heartbeat. RESULTS: The PRS, PCS, EPRS, and EPCS of the sham group increased after LDD injection. However, the PRS, PCS, EPRS, and EPCS of the IMH segment did not increase. Moreover, the PRS and PCS of the MI and NMI segments did not increase, but the EPRS and EPCS of these segments increased. The PRS, PCS, EPRS, and EPCS of the IMH segment were lower than those of the MI and NMI segments before and after LDD injection, but without a significant difference between MI segment and NMI segment before and after LDD injection. CONCLUSIONS: LDD could help assess dysfunctions in segments with IMH, especially using the efficiency of strain. IMH was a crucial factor that decreased segmental movement and reserved function.

A piperidinol-containing molecule is active against Mycobacterium tuberculosis by inhibiting the mycolic acid flippase activity of MmpL3.

Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major human pathogen, and current treatment options to combat this disease are under threat because of the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. High-throughput whole-cell screening of an extensive compound library has recently identified a piperidinol-containing molecule, PIPD1, as a potent lead compound against M. tuberculosis Herein, we show that PIPD1 and related analogs exert in vitro bactericidal activity against the M. tuberculosis strain mc26230 and also against a panel of multidrug-resistant and extensively drug-resistant clinical isolates of M. tuberculosis, suggesting that PIPD1's mode of action differs from those of most first- and second-line anti-tubercular drugs. Selection and DNA sequencing of PIPD1-resistant mycobacterial mutants revealed the presence of single-nucleotide polymorphisms in mmpL3, encoding an inner membrane-associated mycolic acid flippase in M. tuberculosis Results from functional assays with spheroplasts derived from a M. smegmatis strain lacking the endogenous mmpL3 gene but harboring the M. tuberculosis mmpL3 homolog indicated that PIPD1 inhibits the MmpL3-driven translocation of trehalose monomycolate across the inner membrane without altering the proton motive force. Using a predictive structural model of MmpL3 from M. tuberculosis, docking studies revealed a PIPD1-binding cavity recently found to accommodate different inhibitors in M. smegmatis MmpL3. In conclusion, our findings have uncovered bactericidal activity of a new chemical scaffold. Its anti-tubercular activity is mediated by direct inhibition of the flippase activity of MmpL3 rather than by inhibition of the inner membrane proton motive force, significantly advancing our understanding of MmpL3-targeted inhibition in mycobacteria.

MR extracellular volume mapping and non-contrast T1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys.

OBJECTIVE: To detect diffuse myocardial fibrosis in different severity levels of left ventricular diastolic dysfunction (DD) in spontaneous type 2 diabetes mellitus (T2DM) rhesus monkeys. METHODS: Eighteen spontaneous T2DM and nine healthy monkeys were studied. Echocardiography was performed for diastolic function classification. Cardiac magnetic resonance (CMR) imaging was performed to obtain extracellular volume fraction (ECV) maps and T1ρ maps at two different spin-locking frequencies. ECV values, T1ρ values, and myocardial fibrosis index (mFI) values which are based on the dispersion of T1ρ, were calculated. Global peak diastolic longitudinal strain rates (GSrL) were also obtained. RESULTS: Echocardiography results showed mild DD in nine T2DM monkeys and moderate DD in the other nine. The global ECV values were significantly different among healthy animals as compared with animals with mild DD or moderate DD, and the ECV values of animals with moderate DD were significantly higher as compared with those of mild DD. The mFI values increased progressively from healthy animals to those with mild DD and then to those with moderate DD. Diastolic function indicators (e.g., early diastolic mitral annulus velocity, GSrL) correlated well with ECV and mFI. CONCLUSIONS: Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. T1ρ mapping may have the potential to be used for diffuse myocardial fibrosis assessment. KEY POINTS: • Monkeys with T2DM exhibit increased ECV, T1ρ, and mFI values, which may be indicative of the expansion of extracellular volume and the deposition of excessive collagen. • The relationship between diastolic dysfunction and diffuse myocardial fibrosis may be demonstrated by imaging markers. • Non-contrast T1ρ mapping may have the potential to be used for diffuse myocardial assessment.

[Cardiac Magnetic Resonance in Cardiovascular Disease Research and Its Clinical Application: an Update].

Cardiac magnetic resonance (CMR) is a non-invasive imaging technology, which has been used widely in clinical and basic researches on cardiovascular disease in recent years. With the innovation and optimization of CMR technologies, significant progress has been developed in the evaluation of myocardial viability, the function of regions and global myocardium, and the myocardial texture characteristics. Therefore, with the discussion on the progress of CMR to draw more and more attention in clinics, we hope to improve the application of CMR not only in the basic research but also in the diagnosis and precise evaluation aspects of cardiovascular disease.

[Cardiac Magnetic Resonance Imaging Study of Ventricular Myocardial Deformation in Spontaneous T2DM Rhesus Monkey].

OBJECTIVE: To assess biventricular, especially right ventricular, function and deformationin rhesus monkeys with spontaneous type 2 diabetes mellitus (T2DM) using cardiac magnetic resonance (CMR). METHODS: Twelve male spontaneous T2DM rhesus monkeys and age, sex, body mass matched 9 healthy rhesus monkeys without hypertension and myocardial infarction were included in this study. Fasting blood glucose (FPG), glycated hemoglobin (HbA1c) and blood liquid levels were measured. Biventricular function and myocardial deformations were evaluated by CMR cine and tissue-tracking. RESULTS: Compared with control, the FPG and HbA1c levers were significantly increased in T2DM group, but there was no significant difference in body mass and age between the two groups. CMR result showed that there was no significant decrease in right ventricle and left ventricle ejection fraction in T2DM (P < 0.05). However, the absolute value of radial and circumferential global peak systolic strain, systolic strain rate and three directions global peak diastolic strain rate of the right ventricle free wall were lower in the T2DM group (P < 0.05). Also, only radial and circumferential peak systolic strain and radial diastolic strain rate of left ventricle were higher (P < 0.05). CONCLUSIONS: Right ventricle showed systolic and diastolic dysfunction which were consistent with left ventricle in T2DM by CMR-tissue tracking.

[Magnetic Resonance Imaging Tissue Feature Tracking for Cardiac Amyloidosis].

OBJECTIVE: To detect cardiac amyloidosis (CA) using cardiac magnetic resonance feature tracking(CMR-FT). METHODS: Forty-three CA patients and 24 healthy volunteers underwent steady-state free precession cine sequence on 3.0T MRI after injection of Magnevist. Software cvi 42 was used for analyzing the left ventricular function including left ventricular mass (diastole) (LVMD), left ventricular mass (systole) (LVMS), left ventricle end-diastolic volume (LVEDV), left ventricle end-systolic volume (LVESV), left ventricle stroke volume (LVSV), and left ventricular ejection fraction (LVEF), as well as myocardial strains including 3D global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS), and 2D endocardial and epicardial longitudinal strain, circumferential strain, and radial strain (ENDO-LS, EPI-LS, ENDO-CS, EPI-CS, ENDO-RS, and EPI-RS). The global and layer-specific strains were compared between the CA patients with LVEF >50%, the CA patients with LVEF ≤50%, and the healthy controls. RESULTS: For the left ventricular function, the CA patients had greater myocardial mass than the healthy controls (P < 0.05); the CA patients with LVEF ≤50% had greater LVESV and lower LVSV than those with LVEF >50% (P < 0.05). For the global strains, significant differences also appeared in GLS and GCS among the three groups (all P < 0.05). The CA patients had lower GRS than the healthy controls (P < 0.05), while no significant difference was found in GRS between the CA patients with LVEF >50% and those with LVEF ≤50% (P>0.05). For the layer-specific strains, significant differences in ENDO-LS, EPI-LS, ENDO-CS, EPI-CS, ENDO-RS, and EPI-RS were found among the three groups (all P < 0.05). There were significant correlations between GLS and LVEF (r=-0.404, P=0.016), and between GCS and LVEF (r=-0.602, P < 0.001) in the CA patients. CONCLUSION: CMR-FT can assess not only global strains but also layer-specific strains for the myocardial function of CA patients.

[Diagnostic Values and Reliability of Cardiac Magnetic Resonance Tissue Tracking 2D and 3D Strain Assessments for Experimental Autoimmune Myocarditis in Rats].

OBJECTIVE: To determinethe diagnostic valuesand reliabilityof cardiac magnetic resonance tissue tracking (CMR-TT) derived two-dimensional(2D) and three-dimensional(3D) strains in assessing experimental autoimmunity myocarditis (EAM) in rats. METHODS: 20 Lewis rats were randomly divided into model and control groups. The animal model of autoimmune myocarditis was induced by injecting porcine cardiac myosin into the footpads of the rats.On day 35, all of the rats were examined using the 7.0T CMR cine scan. The cardiac function and global strain of the left ventricular of the rats were analyzed with specific cardiac post-processing. The rats were then sacrificed and myocardial samples were taken and stained with HE and Masson. The diagnostic values of the strain parameters were assessed by receiver operating characteristic (ROC) curves with the pathological results as diagnostic criteria.The reliability of the strain parameters were tested using interclass correlation coefficient (ICC), coefficients of variation (CV) and Bland-Altman. RESULTS: No abnormal pathological changes in myocardial cells were found in the control group. Myocarditis was successfully induced in all of the rats in the model group, showing myocardial fiber arrangement disorder, degeneration, necrosis, inflammatory cell infiltration and interstitial fibrosis. The ROC showed that 2D global strain parameters possessed higher diagnostic values than 3D strain parameters. The 2D had an area under the curve (AUC) of 0.96 in global circumferential strain (GCS), 0.95 in global radial strain (GRS), and 0.90 in global longitudinal strain (GLS), compared with 0.87 GCS, 0.85 GRS, and 0.77 GLS in the 3D, respectively.The reliability of the 2D strain parameters was high, except for inter-observer 2D GRS(ICC=0.893). The 3D strain parameters had lower reliability (ICCs:0.421-0.79) than the 2D strain parameters (ICCs:0.893-0.986). CONCLUSION: The diagnostic values of 2D strain parameters are higher than 3D strain parameters in diagnosing myocarditis.

[Evaluating Cardiac Function of Tree Shrew (Tupaiabelangeri) using CMR at 7T with 2D Tissue Tracking].

OBJECTIVE: To determine the potential value of the two-dimensional (2D) cardiac magnetic resonance imaging (CMR) tissue tracking (CMR-TT) method in assessing the cardiac function of tree shrew at 7T. METHODS: Healthy adult tree shrews (male, n=8) and spraguedawley rats(male, n=8) were selected for this study. CMR was performed to acquire the short-axis images of left ventricle at 7T using the same appropriative coil and cine sequence for all experimental animals. The CMR images were processed using the professional cardiac analysis software, calculating ejection fraction (EF), radial peak sysolic strain (Err), circumferential peak sysolic strain (Ecc), radial peak sysolic displacement (DR), and LVM/BM 〔the ratio of left ventricular mass (LVM) to body mass (BM)〕. RESULTS: Cine imaging for the tree shrews was 100% successful following the CMR protocol for the rats, with clearly visible main segments of cardiac. Significant differences in EF, Err, Ecc and DR were found between the two groups of animals (P < 0.01). The tree shrews has lower EF, Err and Ecc than the rats. Err and Ecc appeared in the fifteenth phase in left ventriclar systole in the tree shrews, compared with the tenth phase in the rats.The tree shrews also had higher LVM/BM than the rats. CONCLUSION: The cardiac function of tree shrew can be assessed using the 2D CMR-TT method despite significant differences across species.

[Tracking Early Reperfused Myocardial Infarction using Cardiac MR].

OBJECTIVE: To determine segmental myocardial changes in cardiovascular magnetic resonance feature-tracking (CMR-FT) in the early phase of reperfused myocardial infarction in patients and rats. METHODS: Ten patients receiving percutaneous coronary interventions (2-10 d) and 10 rats with 60 min induced myocardial ischemia followed by reperfusions (48 h and 7 d) were investigated by MRI. The steady state free precession cine and late gadolinium enhancement (LGE) sequences were measured to evaluate the standard short axis of the whole heart after an injection of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, Magnevist, Bayer Health Care Pharmaceuticals) at a dose of 0.1 mmol/kg. The infarction sizes (all areas were expressed as a percentage of the whole myocardial tissues of left ventricle (LV), end-diastolic volume (EDV) and ejection fractions (EF) were calculated. The MRI cine images were analyzed using the myocardial feature tracking software CVI, estimating the peak value of radial strains (RS) and circumferential strains (CS) of the 16 AHA segments excluding apex cordis. The complete myocardial infarction (CMI) segments, partial myocardial infarction (PMI) segments and non-myocardial infarction (NMI) segments were identified and compared. RESULTS: Patients: The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (both P < 0.01). However, there was no significant difference between the CMI and the PMI segment (P>0.05). Rats: No significance differences were found in EF and EDV between the two time period 48 h and 7 d (both P>0.05). The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (all P < 0.01). But there was no significance difference between the CMI segment and the PMI segment (P>0.05). No significant changes in the global radial strain and the circumferential strain were found over time (both P>0.05). But the segmental radial strain and circumferential strain became larger over time (all P < 0.05). CONCLUSIONS: The systolic ability of myocardium decreases as a result of reperfusion injury in the early phase of reperfused myocardial infarction. But it can gradually recover over time with reperfusion.

2D/3D CMR tissue tracking versus CMR tagging in the assessment of spontaneous T2DM rhesus monkeys with isolated diastolic dysfunction.

BACKGROUND: Spontaneous T2DM in rhesus monkeys manifests as isolated diastolic dysfunction in the early stage of diabetic cardiomyopathy, similar to humans. Myocardial deformation measurements have emerged as a superior way to measure left ventricular (LV) function in the early stage of cardiac dysfunction, making it possible to further evaluate early-stage LV dysfunction in spontaneous T2DM rhesus monkeys. METHODS: Spontaneous T2DM rhesus monkeys with isolated diastolic dysfunction (T2DM-DD, n = 10) and corresponding nondiabetic healthy animals (ND, n = 9) were prospectively scanned for a CMR study. Circumferential and longitudinal peak systolic strain (Ecc, Ell), time to peak strain (tEcc, tEll) and peak diastolic strain rate (CSR, LSR) obtained from 2D/3D CMR-TT were compared with those obtained from CMR tagging separately. In addition, all CMR imaging protocols were performed twice in 9 ND animals to assess test-retest reproducibility. RESULTS: Compared with the ND group, the T2DM-DD monkeys demonstrated significantly impaired LV Ecc (- 10.63 ± 3.23 vs - 14.18 ± 3.19, p < 0.05), CSR (65.50 ± 14.48 vs 65.50 ± 14.48, p < 0.01), Ell (- 9.11 ± 2.59 vs - 14.17 ± 1.68, p < 0.05), and LSR (59.43 ± 19.17 vs 108.46 ± 22.33, p < 0.01) with the tagging. Only Ecc (- 13.10 ± 2.47 vs - 19.03 ± 3.69, p < 0.01) and CSR (148.90 ± 31.27 vs 202.00 ± 51.88, p < 0.01) were significantly reduced with 2D CMR-TT, and only Ecc (- 13.77 ± 1.98 vs - 17.26 ± 3.78, p < 0.05) was significantly reduced with 3D CMR-TT. Moreover, 2D/3D CMR-TT-derived Ecc and CSR correlated with the corresponding tagging values collectively, with a statistically significant ICC value (p < 0.05). Test-retest repeatability analysis showed that most tagging-derived biomarkers had acceptable repeatability (p < 0.01). In addition, 2D CMR-TT-derived indicators were poorer than those derived from the tagging method but better than those obtained using the 3D method, with larger ICCs except for tEcc (p < 0.05). CONCLUSIONS: LV systolic and diastolic deformations were impaired in spontaneous T2DM rhesus monkeys previously diagnosed with isolated diastolic dysfunction by echocardiography. The 2D CMR-TT-derived Ecc and CSR were effective in the evaluation of the myocardial systolic and diastolic functions of early-diabetic cardiomyopathy, with relatively higher test-retest reproducibility and acceptable correlation with the tagging method compared with the 3D CMR-TT method.

Subunit composition of a DEG/ENaC mechanosensory channel of Caenorhabditis elegans.

Caenorhabditis elegans senses gentle touch in the six touch receptor neurons (TRNs) using a mechanotransduction complex that contains the pore-forming degenerin/epithelial sodium channel (DEG/ENaC) proteins MEC-4 and MEC-10. Past work has suggested these proteins interact with the paraoxonase-like MEC-6 and the cholesterol-binding stomatin-like MEC-2 proteins. Using single molecule optical imaging in Xenopus oocytes, we found that MEC-4 forms homotrimers and MEC-4 and MEC-10 form 4:4:10 heterotrimers. MEC-6 and MEC-2 do not associate tightly with these trimers and do not influence trimer stoichiometry, indicating that they are not part of the core channel transduction complex. Consistent with the in vitro data, MEC-10, but not MEC-6, formed puncta in TRN neurites that colocalize with MEC-4 when MEC-4 is overexpressed in the TRNs.

The quantification of blood-brain barrier disruption using dynamic contrast-enhanced magnetic resonance imaging in aging rhesus monkeys with spontaneous type 2 diabetes mellitus.

Microvascular lesions of the body are one of the most serious complications that can affect patients with type 2 diabetes mellitus. The blood-brain barrier (BBB) is a highly selective permeable barrier around the microvessels of the brain. This study investigated BBB disruption in diabetic rhesus monkeys using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Multi-slice DCE-MRI was used to quantify BBB permeability. Five diabetic monkeys and six control monkeys underwent magnetic resonance brain imaging in 3 Tesla MRI system. Regions of the frontal cortex, the temporal cortex, the basal ganglia, the thalamus, and the hippocampus in the two groups were selected as regions of interest to calculate the value of the transport coefficient Ktrans using the extended Tofts model. Permeability in the diabetic monkeys was significantly increased as compared with permeability in the normal control monkeys. Histopathologically, zonula occludens protein-1 decreased, immunoglobulin G leaked out of the blood, and nuclear factor E2-related factor translocated from the cytoplasm to the nuclei. It is likely that diabetes contributed to the increased BBB permeability.

The role of curvature effects in liquid-liquid extraction: assessing organic phase mesoscopic properties from MD simulations.

The bending rigidity of small reverse aggregates involved in liquid-liquid extraction processes has been investigated by molecular dynamics simulations. Simulations of a common extractant (DMDOHEMA) with four hydrophobic chains in explicit solvent (n-heptane) and in vacuum have been performed to determine the effect of solvent penetration on film stiffness. Elastic film bending energy that is needed for mesoscopic modelling of transfer of species between complex fluids is harmonic in terms of curvature (Helfrich formalism) and the packing parameter only if the solvent is explicitly taken into account. In terms of the packing parameter of the real molecular film constituting the reverse water in oil aggregates and taking into account molecular volume, area and film thickness (that is in agreement with Tanford's model), the bending rigidity is calculated to be about 16 kBT per extractant molecule (about 40 kJ mol-1), which is smaller than the free energy of transfer from an isolated "monomer" molecule to a weak aggregate, but of the order of magnitude of the free energy of transfer used in liquid-liquid extraction processes.

Stability of reverse micelles in rare-earth separation: a chemical model based on a molecular approach.

Molecular complexes formed in the organic phase during solvent extraction may self-assemble as reverse micelles, and therefore induce a supramolecular organization of this phase. In most of the cases, water molecules play an essential role in the organization of this non polar medium. The aim of this work is to investigate the speciation of the aggregates formed in the organic phase during solvent extraction, and especially to assess their stability as a function of the number of water molecules included in their polar core. We have focused on malonamide extractants that have already been investigated experimentally. Different stoichiometries of reverse micelles in the organic phase have been studied by means of classical molecular dynamics simulations. Furthermore, umbrella-sampling molecular dynamics simulations have been used to calculate the equilibrium constant (K°) representing the association/dissociation pathways of water molecules in the aggregates and the corresponding reaction free energies (ΔrG°).