miR-152 regulates the proliferation and differentiation of C2C12 myoblasts by targeting <Emphasis Type="Italic">E2F3</Emphasis>

The development of skeletal muscle is a complex process involving the proliferation, differentiation, apoptosis, and changing of muscle fiber types in myoblasts. Many reports have described the involvement of microRNAs in the myogenesis of myoblasts. In this study, we found that the expression of miR-152 was gradually down-regulated during myoblast proliferation, but gradually up-regulated during the differentiation of myoblasts. Transfection with miR-152 mimics restrained cell proliferation and decreased the expression levels of cyclin E, CDK4, and cyclin D1, but promoted myotube formation and significantly increased the mRNA expression levels of MyHC, MyoD, MRF4, and MyoG in C2C12 myoblasts. However, treatment with miR-152 inhibitors promoted cell proliferation and restrained differentiation. Moreover, over-expression of miR-152 significantly decreased E2F3 production in C2C12 myoblasts. A luciferase assay confirmed that miR-152 could bind to the 3′ UTR of E2F3. In conclusion, this study showed that miR-152 inhibited proliferation and promoted myoblast differentiation by targeting E2F3.     

Nutrient Balancing by Captive Golden Snub-Nosed Monkeys <Emphasis Type="Italic">(Rhinopithecus roxellana</Emphasis>)

An organism’s fitness is tied closely to its ability to obtain food. However, many foods are nutritionally suboptimal on their own, forcing an individual to develop a feeding strategy that actively manages both type and amount of food consumed. Animals in captivity are additionally limited to human provisioned diets, which may be nutritionally inadequate and negatively affect behavior and health. We studied the nutritional intake of captive golden snub-nosed monkeys (Rhinopithecus roxellana) at two locations in China (132 days of continuous, sunrise to sunset focal samples of 7 individuals at each site) and used the Geometric Framework for nutrition to identify their feeding strategy and evaluate diet variation across sites, seasons, and age–sex classes. Captive golden snub-nosed monkeys had a mean nutrient intake of 75% carbohydrates (15% neutral detergent fiber, 60% total nonstructural carbohydrates), 12% fat, and 13% protein (by energy) that differed by location and season owing to differences in the type and amount of food items offered and consumed. Intake at one location differed from that of wild golden snub-nosed monkeys, suggesting that the captive diet was inadequate. These results highlight the importance of developing nutritionally adequate diets for captive animals based on an understanding of their nutritional requirements.     

Understanding the structural and energetic basis of PD-1 and monoclonal antibodies bound to PD-L1: A molecular modeling perspective

Background

The inhibitors blocking the interaction between programmed cell death protein 1(PD-1) and programmed death-ligand 1(PD-L1) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L1 and its protein ligands. However, the hotspot residues on PD-L1 as well as structural and energetic basis for different protein ligands still need to be further investigated.

伞形科部分类群气孔结构及其分类学价值

该研究对变豆菜亚科及芹亚科基础类群20属29种(变豆菜亚科9属11种,芹亚科基础类群11属18种)植物叶片(苞片或果实)的气孔结构进行显微观察分析,以明确变豆菜亚科及芹亚科基础类群的气孔特征及其与伞形科其他类群的区别。结果显示:(1)变豆菜亚科及芹亚科基础类群的气孔类型有无规则型、不等型和平列型3种,其中变豆菜亚科的变豆菜族气孔为无规则型(占总气孔比例的35%~75%)及不等型(25%~65%),仅刺芹属(Eryngium)具平列型,而Steganotaenieae族的气孔均为无规则型;芹亚科基础类群除柴胡属(Bupleurum)外多为或仅为无规则型(75%~100%),少为不等型(5%~25%)。(2)气孔结构支持分子系统学将Arctopus放入变豆菜亚科的变豆菜族,Choritaenia移入芹亚科。(3)变豆菜亚科气孔特征同芹亚科及牵环花亚科的较为相似,而同参棕亚科差别较大。     

Differentiation of Breast Cancer from Fibroadenoma with Dual-Echo Dynamic Contrast-Enhanced MRI

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) of the breast is a routinely used imaging method which is highly sensitive for detecting breast malignancy. Specificity, though, remains suboptimal. Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI), an alternative dynamic contrast imaging technique, evaluates perfusion-related parameters unique from DCE MRI. Previous work has shown that the combination of DSC MRI with DCE MRI can improve diagnostic specificity, though an additional administration of intravenous contrast is required. Dual-echo MRI can measure both T₁W DCE MRI and T₂*W DSC MRI parameters with a single contrast bolus, but has not been previously implemented in breast imaging. We have developed a dual-echo gradient-echo sequence to perform such simultaneous measurements in the breast, and use it to calculate the semi-quantitative T₁W and T₂*W related parameters such as peak enhancement ratio, time of maximal enhancement, regional blood flow, and regional blood volume in 20 malignant lesions and 10 benign fibroadenomas in 38 patients. Imaging parameters were compared to surgical or biopsy obtained tissue samples. Receiver operating characteristic (ROC) curves and area under the ROC curves were calculated for each parameter and combination of parameters. The time of maximal enhancement derived from DCE MRI had a 90% sensitivity and 69% specificity for predicting malignancy. When combined with DSC MRI derived regional blood flow and volume parameters, sensitivity remained unchanged at 90% but specificity increased to 80%. In conclusion, we show that dual-echo MRI with a single administration of contrast agent can simultaneously measure both T₁W and T₂*W related perfusion and kinetic parameters in the breast and the combination of DCE MRI and DSC MRI parameters improves the diagnostic performance of breast MRI to differentiate breast cancer from benign fibroadenomas.     

Identification of lipid binding and lipoprotein lipase activation domains of human apoAV

ApoAV, a newly discovered apolipoprotein, plays a key role in human triglyceride homeostasis; however, the structure-function correlation of apoAV is not clearly understood. To explore the relationship, wild type and six deletion mutants, that is (AV (Delta(1-51)), AV (Delta(51-128)), AV (Delta(132-188)), AV (Delta(192-238)), AV (Delta(246-299)), AV (Delta(301-343))), of human apoAV expressed in Escherichia coli were studied. All the deleted regions together encompass almost the entire 343 amino acid sequence of wild type apoAV. Circular dichroism spectroscopy showed that the alpha helical content of lipid-free wild type apoAV was 46%. In comparison with wild type apoAV, AV (Delta(192-238)) and AV (Delta(301-343)) displayed significantly decreased lipid binding activities, confirming the importance of these two regions in lipid binding function of apoAV. While, the LPL activation function of apoAV remarkably impaired after deletion of residues 192-238. These findings suggested that the domain (192-238) is absolutely necessary for apoAV in lipid binding and lipoprotein lipase activation.     

The Relative Contribution of Paracine Effect versus Direct Differentiation on Adipose-Derived Stem Cell Transplantation Mediated Cardiac Repair

Background

Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC) can improve cardiac function in animal models of myocardial infarction (MI). However, the mechanisms underlying the beneficial effect are not fully understood. In this study, we characterized the paracrine effect of transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair.

Methodology/Principal Findings

MI was experimentally induced in mice by ligation of the left anterior descending coronary artery. Either human ADSC, conditioned medium (CM) collected from the same amount of ADSC or control medium was injected into the peri-infarct region immediately after MI. Compared with the control group, both ADSC and ADSC-CM significantly reduced myocardial infarct size and improved cardiac function. The therapeutic efficacy of ADSC was moderately superior to ADSC-CM. ADSC-CM significantly reduced cardiomyocyte apoptosis in the infarct border zone, to a similar degree with ADSC treatment. ADSC enhanced angiogenesis in the infarct border zone, but to a stronger degree than that seen in the ADSC-CM treatment. ADSC was able to differentiate to endothelial cell and smooth muscle cell in post-MI heart; these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found.

Conclusions

ADSC-CM is sufficient to improve cardiac function of infarcted hearts. The therapeutic function of ADSC transplantation is mainly induced by paracrine-mediated cardioprotection and angiogenesis, while ADSC differentiation contributes a minor benefit by being involved in angiogenesis. Highlights 1 ADSC-CM is sufficient to exert a therapeutic potential. 2. ADSC was able to differentiate to vascular cells but not cardiomyocyte. 3. ADSC derived vascular cells amount to about 9% of the enhanced angiogenesis. 4. Paracrine effect is the major mechanism of ADSC therapeutic function for MI.     

Characterization and Fine Mapping of GLABROUS RICE 2 in Rice

Glabrous rice exhibits glabrous leaves and hulls because neither of these structures have trichomes on their surfaces. Glabrous rice varieties have become an important germplasm resource in the rice industry because they have considerable packaging efficiency and can reduce skin itching and dust during harvesting, drying, and packing （Shim et al., 2012; Zhang et al., 2012）.     

Myeloid cell-specific ABCA1 deletion does not worsen insulin resistance in HF diet-induced or genetically obese mouse models

Obesity-associated low-grade chronic inflammation plays an important role in the development of insulin resistance. The membrane lipid transporter ATP-binding cassette transporter A1 (ABCA1) promotes formation of nascent HDL particles. ABCA1 also dampens macrophage inflammation by reducing cellular membrane cholesterol and lipid raft content. We tested the hypothesis that myeloid-specific ABCA1 deletion may exacerbate insulin resistance by increasing the obesity-associated chronic low-grade inflammation. Myeloid cell-specific ABCA1 knockout (MSKO) and wild-type (WT) mice developed obesity, insulin resistance, mild hypercholesterolemia, and hepatic steatosis to a similar extent with a 45% high-fat (HF) diet feeding or after crossing into the ob/ob background. Resident peritoneal macrophages and stromal vascular cells from obese MSKO mice accumulated significantly more cholesterol. Relative to chow, HF diet markedly induced macrophage infiltration and inflammatory cytokine expression to a similar extent in adipose tissue of WT and MSKO mice. Among pro-inflammatory cytokines examined, only IL-6 was highly upregulated in MSKO-ob/ob versus ob/ob mouse peritoneal macrophages, indicating a nonsignificant effect of myeloid ABCA1 deficiency on obesity-associated chronic inflammation. In conclusion, myeloid-specific ABCA1 deficiency does not exacerbate obesity-associated low-grade chronic inflammation and has minimal impact on the pathogenesis of insulin resistance in both HF diet-induced and genetically obese mouse models.