assessment-cardiac-morphological-functional-changes-mouse-model

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging

Transverse aortic constriction (TAC) in mice has been used as a valuable model to study mechanisms of cardiac hypertrophy and heart failure1. A reliable ...

University of Washington

In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and angle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activities of animals weren't influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.

Intravesical instillation in pure line LEW rats and nude mice.

Emerging evidence from therapeutic trials in humans and animal models suggests that in the treatment of depression, antidepressants play a role by targeting the glutamatergic system. Fluvoxamine is one of the widely used SSRIs which has been considered to target monoamine neurotransmitter reuptake mechanisms. However, whether fluvoxamine has an effect on the glutamate release is still unclear. The present experiment studied the effect of fluvoxamine on presynaptic glutamate release in prelimbic cortex, both in control C57BL/6 mice and chronic restraint stress C57BL/6 mice, and further investigated the mechanism underlying this effect by using patch clamp, on-line fluorimetry, pharmacological approaches combined with other techniques. The results showed that fluvoxamine increased the glutamate release in the depression model mice but it had no effect on the glutamate release in the control mice. The mechanism underlying these effects in depression model mice was that, fluvoxamine firstly activated presynaptic 5-HT(3) receptors, which transiently increased the Ca(2+) concentration. The increase of Ca(2+) concentration via 5-HT(3) receptors caused the activation of sigma-1 receptors, which were activated by fluvoxamine. The activation of sigma-1 receptors increased the intrasynaptosomal Ca(2+) concentration significantly through the outflow of endoplasmic reticulum calcium and finally activated PKC. These results suggested that fluvoxamine may have a selective effect and different mechanism based on the condition of animal.

Fluvoxamine increased glutamate release by activating both 5-HT(3) and sigma-1 receptors in prelimbic cortex of chronic restraint stress C57BL/6 mice.

In the differentiating alphaproteobacterium Caulobacter crescentus, organelle synthesis at cell poles is critical to forming different progeny after cell division. Co-ordination of polar organelle synthesis, including pili and holdfast, and flagellum ejection, is mediated in part by the scaffolding protein PodJ. At the time of cell division, PodJ undergoes regulated processing to a short form that persists at the flagellar pole of swarmer cells. This study analyses how PodJ's role in structural and signalling protein localization impacts organelle synthesis. A PodJ mutant with an internal deletion exhibits reduced sensitivity to pili-tropic phage ΦCbK, resulting from reduced pilA gene expression, which can be linked to altered signalling protein localization. The phage sensitivity defect of a ΔpodJ mutant can be partially suppressed by ectopic pilA expression. Induction of PodJ processing, by manipulation of podJ itself or controlled perP expression, resulted in decreased pilus biogenesis and, when coupled with a podJ mutation that reduced pilA expression, led to complete loss of phage sensitivity. As a whole, the results show that PodJ's scaffolding role for structural and signalling proteins both contribute to flagellar pole organelle development.

The scaffolding and signalling functions of a localization factor impact polar development.

Inflammation contributes to the pathophysiology of depression. Chemokine-like receptor-1 (CMKLR1) plays an important role both in the development of inflammation and in the mechanism of antidepressant effect of Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), ecosapeatanolicacid (EPA). The present study was to investigate the modification of CMKLR1 in chronic restraint stress (CRS) rats. CMKLR1 was examined in different brain region from CRS rats by using western blot and quantitative real-time PCR. The CMKLR1 expression in the hippocampus, prefrontal cortex and cerebellum was determined on 3, 7, 10 and 21 days of repeated restraint stress and was compared to controls. The results showed that the protein and mRNA level of CMKLR1 in the prefrontal cortex and hippocampus were significantly increased on day 3 and then decreased on day 7, 10 and 21 in the CRS rats. The protein and mRNA level of CMKLR1 in cerebellum was similar to that of control group throughout the whole experiment. Changed expression of brain CMKLR1 is suggested to be involved in the mechanism of depression.

Chronic mild restraint stress rats decreased CMKLR1 expression in distinct brain region.

A simple approach is presented for the fabrication of poly(methyl methacrylate) (PMMA) nanobowl arrays over cm2 areas using SiO2 colloidal crystal templates. SiO2 colloidal crystal templates were prepared on a clean glass substrate by self-assembled SiO2 spheres of 410 nm in diameter. The air between the silica spheres was filled by the superfluous monomer of PMMA that can be subsequently polymerized. After infiltration, the SiO2-PMMA templates were immersed in a 3 wt% hydrofluoric acid (HF) aqueous solution. After 24 h, silica spheres were etched and a free-standing nanobowl sheet was obtained. The size of the nanobowls could be controlled by the size of the SiO2 spheres and the area of the nanobowl sheet could be altered by the size of the glass substrate.

Fabrication of ordered poly(methyl methacrylate) nanobowl arrays using SiO2 colloidal crystal templates.

Peptide deformylase (PDF) is a prokaryotic enzyme that catalyzes the deformylation of nascent peptides generated during protein synthesis and water molecules play a key role in these hydrolases. Using X-ray absorption near edge spectroscopy (XANES) and ab initio calculations we accurately probe the local atomic environment of the metal ion binding in the active site of PDF at different pH values and with different metal ions. This new approach is an effective way to monitor existing correlations among functions and structural changes. We show for the first time that the enzymatic activity depends on pH values and metal ions via the bond length of the nearest coordinating water (Wat1) to the metal ion. Combining experimental and theoretical data we may claim that PDF exhibits an enhanced enzymatic activity only when the distance of the Wat1 molecule with the metal ion falls in the limited range from 2.15 to 2.55 Å.

How water molecules affect the catalytic activity of hydrolases--a XANES study of the local structures of peptide deformylase.

Chitosan oligosaccharide (COS) has a blood glucose lowering effect in diabetic rats and is widely used as a dietary supplement. However, the effect of COS on the offspring of supplemented mothers is unknown. This experiment investigates the effect of supplementing sows during gestation and lactation on the levels of plasma glucose on suckling piglets. From day 85 of gestation to day 14 of lactation, 40 pregnant sows were divided into two treatment groups and fed either a control diet or a control diet containing 30mgCOS/kg. One 14 day old piglet per pen was selected to collect plasma and tissue (8pens/diet). Performance, hepatic gluconeogenesis genes and proteins expression, amino acids contents in sow milk, hepatic glycogen and free fatty acid were determined. Results showed that supplementation of the maternal diet with COS improved daily gain and weaning weight (P<0.05), and the concentration of amino acids in sow milk (P<0.05). Meanwhile, maternal supplementation with COS increased (P<0.05) mRNA expression levels and activities of PEPCK-C, PEPCK-M and G6Pase in the liver of piglets compared with piglets from control fed sows. Correspondingly, the level of plasma glucose was higher (P<0.001) and hepatic glycogen was lower (P<0.05) in piglets from COS fed sows when compared with that in the control group. In conclusion, dietary supplementation of the diet with COS during late gestation and lactation reduced piglet hypoglycemia by stimulating hepatic gluconeogenesis and improved the growth rate of suckling piglets.

Supplementation of the sow diet with chitosan oligosaccharide during late gestation and lactation affects hepatic gluconeogenesis of suckling piglets.

Subsyndromal symptomatic depression (SSD) is a common disease with significant social dysfunction. However, SSD is still not well understood and the pathophysiology of it remains unclear.

Down-regulation of PRKCB1 expression in Han Chinese patients with subsyndromal symptomatic depression.

TAK1 (TGFβ-activated kinase-1) signaling is essential in regulating a number of important biological functions, including innate immunity, inflammatory response, cell growth and differentiation, and myocardial homeostasis. The precise role of TAK1 in the adult heart under pathological conditions remains largely unknown. Importantly, we observed that TAK1 is upregulated during compensatory hypertrophy but downregulated in end-stage heart failure. Here we generated transgenic mice with inducible expression of an active TAK1 mutant (TAK1ΔN) in the adult heart. TAK1ΔN transgenic mice developed greater cardiac hypertrophy compared with control mice after transverse aortic constriction (TAC), which was largely blocked by ablation of calcineurin Aβ. Expression of TAK1ΔN also promoted NFAT (nuclear factor of activated T-cells) transcriptional activity in luciferase reporter mice at baseline, which was further enhanced after TAC. Our results revealed that activation of TAK1 promoted adaptive cardiac hypertrophy through a cross-talk between calcineurin-NFAT and IKK-NFκB pathways. More significantly, adult-onset inducible expression of TAK1ΔN protected the myocardium from adverse remodeling and heart failure after myocardial infarction or long-term pressure overload, by preventing cardiac cell death and fibrosis. Mechanistically, TAK1 exerts its cardioprotective effect through activation of NFAT/NFκB, downregulation of Bnip3, and inhibition of cardiac cell death.

TAK1 Regulates Myocardial Response to Pathological Stress via NFAT, NFκB, and Bnip3 Pathways.

Harmful algal blooms caused by Phaeocystis globosa have resulted in staggering losses to coastal countries because of their world-wide distribution. Bacteria have been studied for years to control the blooms of harmful alga, however, the action mechanism of them against harmful algal cells is still not well defined. Here, a previously isolated algicidal bacterium Bacillus sp. LP-10 was used to elucidate the potential mechanism involved in the dysfunction of P. globosa algal cells at physiological and molecular levels. Our results showed Bacillus sp. LP-10 induced an obvious rise of reactive oxygen species (ROS), which was supposed to be major reason for algal cell death. Meanwhile, the results revealed a significant decrease of photosynthetic physiological indexes and apparent down-regulated of photosynthesis-related genes (psbA and rbcS) and protein (PSII reaction center protein D1), after treated by Bacillus sp. LP-10 filtrates, suggesting photoinhibition occurred in the algal cells. Furthermore, our results indicated that light played important roles in the algal cell death. Our work demonstrated that the major lethal reason of P. globosa cells treated by the algicidal bacterium was the photoinhibition resulted from oxidative stress induced by Bacillus sp. LP-10.

Photoinhibition of Phaeocystis globosa resulting from oxidative stress induced by a marine algicidal bacterium Bacillus sp. LP-10.

The energy crisis has become one of the major problems hindering the development of the world. The emergence of microbial fuel cells provides a new solution to the energy crisis. Microbial solar cells, integrating photosynthetic organisms such as plants and microalgae into microbial fuel cells, can convert solar energy into electrical energy. Microbial solar cell has steady electric energy, and broad application prospects in wastewater treatment, biodiesel processing and intermediate metabolites production. Here we reviewed recent progress of microbial solar cells from the perspective of the role of photosynthetic organisms in microbial fuel cells, based on a vast amount of literature, and discussed their advantages and deficiency. At last, brief analysis of the facing problems and research needs of microbial fuel cells are undertaken. This work was expected to be beneficial for the application of the microbial solar cells technology.

[Advances in microbial solar cells--A review].

There is little understanding of how unipolar major depressive disorder (UMDD) symptoms evolve in response to antidepressant treatment. The present research examined the associations between symptom trajectories and clinical remission in Chinese patients with UMDD. A total of 165 outpatients with UMDD received treatment of fluoxetine (20 mg/day) for 6 weeks and were assessed for symptom severity at weeks 1, 2, 4, and 6. We found that patients with UMDD show heterogeneity in treatment response to fluoxetine. Psychomotor retardation is a prominent symptom during the 6 weeks of assessment, and its severity at baseline is negatively associated with clinical remission. © 2016 John Wiley & Sons Australia, Ltd.

The symptom trajectories to clinical remission in Chinese patients with unipolar major depressive disorder.

Thrombospondin-2 (THBS2) and Thrombospondin-4 (THBS4) play an important role in cancer development and progression. However, genetic evidence for their roles in gastric cancer (GC) is lacking. The aim of this study was to explore the association of THBS2/THBS4 polymorphisms with risk and clinicopathological features of GC in a Southeast Chinese population. Eight tagging SNPs in THBS2 and THBS4 were genotyped in 761 GC cases and 739 controls from Chinese case-control sets using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. THBS2/THBS4 mRNA expression was studied in 82 human GC tumors and in mouse stomach tissues by real-time PCR. We found that both THBS2 and THBS4 were abundantly expressed in mouse stomach. THBS4 mRNA expression in human stomach was associated with tumor size (P = 0.002) and tumor-node-metastasis (TNM) (P = 0.010), and THBS2 mRNA expression was associated with the TNM (P = 0.010). Patients with the rs77878919^AG genotype were more prone to developing diffuse-type GC. THBS4 SNPs (rs77878919 and rs7736549) had a modest cumulative effect on the risk of poor prognosis (TNM), with that risk in the highest trend for patients carrying both these unfavorable genotypes. In addition, individuals carrying the THBS4 rs10474606 variant homozygous AA had a modest reduced GC risk. We conclude that THBS2/THBS4 may be functional in playing important role in GC, which was supported by the evidence of the mRNA overexpression in GC and the modest associations of THBS2/THBS4 polymorphisms to GC. These findings might be useful for risk assessment and prognosis prediction of GC.

Xiaoyun Guo

Department of Physiology and Biophysics

University of Washington

Assessment of Cardiac Morphological and Functional Changes in Mouse Model of Transverse Aortic Constriction by Echocardiographic Imaging