Skeletal myopathy in a rat model of postmenopausal heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of all patients with heart failure and frequently affects postmenopausal women. The HFpEF condition is phenotype-specific, with skeletal myopathy that is crucial for disease development and progression. However, most of the current preclinical models of HFpEF have not addressed the postmenopausal phenotype. We sought to advance a rodent model of postmenopausal HFpEF and examine skeletal muscle abnormalities therein. Female, ovariectomized, spontaneously hypertensive rats (SHR) were fed a high fat, high sucrose diet to induce HFpEF. Controls were female sham-operated Wistar-Kyoto rats on a lean diet. In a complementary, longer-term cohort, controls were female sham-operated SHRs on a lean diet to evaluate the effect of strain difference in the model. Our model developed key features of HFpEF that included increased body weight, glucose intolerance, hypertension, cardiac hypertrophy, diastolic dysfunction, exercise intolerance, and elevated plasma cytokines. In limb skeletal muscle, HFpEF decreased specific force by 15-30% (p < 0.05) and maximal mitochondrial respiration by 40-55% (p < 0.05), increased oxidized glutathione by ~2-fold (p < 0.05), and tended to increase mitochondrial H2O2 emission (p = 0.10). Muscle fiber cross-sectional area, markers of mitochondrial content, and indices of capillarity were not different between control and HFpEF in our short-term cohort. Overall, our model of postmenopausal HFpEF recapitulates several key features of the disease. This new model reveals contractile and mitochondrial dysfunction and redox imbalance that are potential contributors to abnormal metabolism, exercise intolerance, and diminished quality of life in patients with postmenopausal HFpEF.

Brillouin Frequency Shift Sensing Technology Used in Railway Strain and Temperature Measurement

This study and verification are based on the Brillouin frequency shift (BFS), which is related to the strain and temperature changes of a single-mode fiber, because such a shifted frequency can be quantitatively measured and converted to strain and temperature differences. We explain the installation of a Brillouin distributed fiber sensing system (DFOS) on an actual operating railway to measure the temperature and strain of the rail. In addition, the measured data were calculated and analyzed, revealing the geometric irregularity of the tested rail and the location of the abnormality. We obtained a temperature difference of 12.1 °C between the temperature distribution of the measured rail and the atmospheric temperature, and there was a 1.5 h delay between the two. We also obtained rail irregularities ranging from −0.3 to +0.4 mm by calculating the slight strain difference of the rail in this test.

Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions

Background Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson’s and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a “prion-like” manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail. Methods Three strains of preformed α-syn fibrils (PFFs) were generated in different buffer conditions which varied in pH and ionic concentrations. The α-syn PFFs were intramuscularly (IM) injected into a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses wild-type human α-syn, and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated. Results The three strains of α-syn PFFs triggered distinct propagation patterns. The fibrils generated in mildly acidic buffer led to the most severe α-syn pathology, degeneration of motor neurons and microgliosis in the spinal cord. Conclusions The different α-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS, which further supports the view that α-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.

Damage Identification Method of Box Girder Bridges Based on Distributed Long-Gauge Strain Influence Line under Moving Load

A new method was proposed for the damage identification of box girder bridges under moving load, wherein the difference of strain influence line (DSIL) was taken as an index to represent the long-gauge strain difference before and after damage. The damage identification theory based on long-gauge strain influence lines was derived for box girder bridges with shear lag effect under consideration, and a regularized index DSIL was proposed for the quantitative identifications of damage location and extent. A series of experiments were carried out to study the influences of speed, vehicle type, and vehicle weight on the damage identification, and the experimental data were obtained by long-gauge fiber Bragg grating strain sensors. Moreover, numerical simulations were performed to confirm the method. The experimental and numerical results show that the method can locate the damage accurately, and quantitatively identify the damage extent under different working conditions. The experimental damage extent is generally slightly higher than the theoretical, with an average identification error smaller than 5%. Additionally, the relative error of damage extent is smaller than 3% under different working conditions. Thus, the effectiveness of this method was verified.

Quasi-Static Shear Test of Hybrid Adhesive Bonds Based on Treated Cotton-Epoxy Resin Layer

This research evaluates the mechanical properties of hybrid adhesive bonds with various 100% cotton fabrics in static and quasi-static conditions and the influence of alkali surface treatment (NaOH) of the cotton fabrics on the mechanical properties. Biological fibers in polymers are characterized by low wettability with the matrix, which decreases mechanical properties. Adhesive bonds usually operate in cyclic stress, which causes irreversible failure before maximal strength. In this paper, a quasi-static test was used to load the adhesive bonds in 5–50% (192–1951 N) and 5–70% (192–2732 N) intervals with 1000 cycles. The results of SEM analysis showed good wettability of alkali treated cotton fabric with NaOH solution in hybrid adhesive bonds. The static test proved the influence of reinforcing cotton fabrics on shear tensile strength against pure resin, i.e., sample Erik up to 19% on 14.90 ± 1.15 MPa and sample Tera up to 21% on 15.28 ± 1.05 MPa. The adhesive bonds with pure resin did not resist either quasi-static tests. Reinforcing cotton fabrics resisted both quasi-static tests, even shear tensile strength increases up to 10% on 16.34 ± 1.24 MPa for the fabric Erik. The results of strain difference of adhesive bonds with Tera and Erik confirmed that a lower value of the difference during cyclic loading positively influenced the ultimate shear tensile strength.

Absence-like epileptic spike-wave discharges in adult Lister Hooded rats and their pharmacological modulation

Efforts to advance translation through pre-clinical behavioural and pharmacological tests prompted attention to rat strain differences. Particularly the use of touchscreen technology for cognitive testing initiated the widespread use of Lister Hooded and Long Evans rats and they differed in pharmacological sensitivity to certain drugs. One possible reason for this rat strain difference could be that Long Evans rats produce high-amplitude spike-wave discharges (SWDs) in their cortical EEG recordings, while no information available about Lister Hooded rats in this regard. As a serendipitous observation, we noticed the presence of SWDs during the EEG recordings of Lister Hooded rats. In this study, therefore, we examined these spontaneous SWDs in two groups of Lister Hooded rats. The number and sum duration of the SWDs were similar to that was observed in other rat strains. We found SWDs during wakefulness, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, their duration was the longest during wakefulness, but their number and sum duration were also high during REM. The GABA-B receptor agonist baclofen exacerbated, while the GABA-B antagonist SCH50911 reduced the occurrence of the recorded SWDs. Typical anti-seizure medications, valproate and diazepam, decreased the number and sum duration of SWDs. Although the two rat strains typically used in touchscreen experiments are similar in term of SWDs, the occurrence and possible pharmacological modulation of SWDs are considerable during their use in behavioural experiments.

Strain difference in transgene-induced tumorigenesis and suppressive effect of ionizing radiation

Transgenic expression in medaka of the Xiphophorus oncogene xmrk, under a pigment cell specific mitf promoter, induces hyperpigmentation and pigment cell tumors. In this study, we crossed the Hd-rR and HNI inbred strains because complete genome information is readily available for molecular and genetic analysis. We prepared an Hd-rR (p53+/−, p53−/−) and Hd-rR HNI hybrid (p53+/−) fish-based xmrk model system to study the progression of pigment cells from hyperpigmentation to malignant tumors on different genetic backgrounds. In all strains examined, most of the initial hyperpigmentation occurred in the posterior region. On the Hd-rR background, mitf:xmrk-induced tumorigenesis was less frequent in p53+/− fish than in p53−/− fish. The incidence of hyperpigmentation was more frequent in Hd-rR/HNI hybrids than in Hd-rR homozygotes; however, the frequency of malignant tumors was low, which suggested the presence of a tumor suppressor in HNI genetic background fish. The effects on tumorigenesis in xmrk-transgenic immature medaka of a single 1.3 Gy irradiation was assessed by quantifying tumor progression over 4 consecutive months. The results demonstrate that irradiation has a different level of suppressive effect on the frequency of hyperpigmentation in purebred Hd-rR compared with hybrids.

Significance of the Asymmetry of the Haltere: A Microscale Vibratory Gyroscope

Nature has evolved a beautiful design for small-scale vibratory gyroscopes in the form of halteres located in the metathorax region of the dipteran flies that detect body rotations based on the Coriolis principle. The specific design of the haltere is in contrast to the existing MEMS vibratory gyroscope, where the elastic beams supporting the proof mass are typically designed with symmetric cross-sections so that there is a mode matching between the actuation and sensing vibrations. The mode matching provides high sensitivity and low bandwidth. Hence, the objective of the manuscript is to understand the mechanical significance of the haltere’s asymmetry. In this study, the distributed Coriolis force and the corresponding bending stress by incorporating the actual mass variations along the haltere length are estimated. In addition, it is hypothesied that sensilla sense the rate of rotation based on the differential strain (difference between the final strain (strain due to the inertial and Coriolis forces) and the reference strain (strain due to inertial force)). This differential strain always occurs either on the dorsal or ventral surface of the haltere and at a distance away from the base, where the campaniform sensilla are located. This study brings out one specific feature—the asymmetric geometry of the haltere structure—that is not found in current vibratory gyroscope designs. This finding will inspire new designs of MEMS gyroscopes that have elegance and simplicity of the haltere along with the desired performance.

Abstract P089: Assessment Of Sensorimotor Function To Establish A Clinically Relevant Animal Model Of Intracerebral Hemorrhage (ICH) Using The Hypertensive Transgenic Rat (mRen2)27

Uncontrolled hypertension is the leading cause of spontaneous ICH and elevated SBP is a strong predictor of poor outcomes in ICH patients. An animal model of the chronically hypertensive, metabolically dysfunctional and pro-inflammatory state of the ICH patient population is needed to advance clinically-relevant ICH research. Transgenic (mRen2)27 rats overexpress the murine Ren2 gene and develop hypertension and metabolic syndrome by 12-14 weeks of age. Indices of diastolic and systolic cardiac function are in decline in (mRen2)27 males by 30 weeks of age, but are preserved in females at this age. To establish whether (mRen2)27 rats exhibit sensorimotor dysfunction as compared with control Sprague Dawley (SD) rats, male and female (mRen2)27 rats underwent corner turn (CT), vibrissae evoked forelimb placing (VEF), cage wire hang (CWH), and open-field (OF) testing for five consecutive weeks starting at 20-weeks of age (n=16; female=8; each strain). Despite the significant between-strain difference in SBP [189 ± 3 mmHg in (mRen2)27 and 119 ± 3 mmHg in SD; p<0.001], there were no significant between-strain differences in sensorimotor testing at weeks 20, 22, 23, and 24 (Table 1). At week 21, a significant between-strain difference was identified isolated to the VEF test (p<0.01). As sensorimotor testing is critical to assess the effect of experimentally-induced ICH in rodent models, the lack of strain differences supports the viability of (mRen2)27 rats as a clinically relevant model for the comparison of ICH superimposition in the two strains at this age without consistent baseline sensorimotor deficits. (Cardiovascular Sci. and Hypertension & Vasc. Res. Ctrs; Neurosurgery)

Genetics of mouse behavioral and peripheral neural responses to sucrose

Mice of the C57BL/6ByJ (B6) strain have higher consumption of, and stronger peripheral neural responses to, sucrose solution than do mice of the 129P3/J (129) strain. To identify quantitative trait loci (QTLs) responsible for this strain difference and evaluate the contribution of peripheral taste responsiveness to individual differences in sucrose intake, we produced an intercross (F2) of 627 mice, measured their sucrose consumption in two-bottle choice tests, recorded the electrophysiological activity of the chorda tympani nerve elicited by sucrose in a subset of F2 mice, and genotyped the mice with DNA markers distributed in every mouse chromosome. We confirmed a sucrose consumption QTL (Scon2, or Sac) on mouse chromosome (Chr) 4, harboring the Tas1r3 gene, which encodes the sweet taste receptor subunit T1R3 and affects both behavioral and neural responses to sucrose. For sucrose consumption, we also detected five new main-effect QTLs Scon6 (Chr2), Scon7 (Chr5), Scon8 (Chr8), Scon3 (Chr9) and a sex-specific QTL Scon9 (Chr15), and an interacting QTL pair Scon4 (Chr1) and Scon3 (Chr9). No additional QTLs for the taste nerve responses to sucrose were detected besides the previously known one on Chr4 (Scon2). Identification of the causal genes and variants for these sucrose consumption QTLs may point to novel mechanisms beyond peripheral taste sensitivity that could be harnessed to control obesity and diabetes.