雷米普利与BQ-123合用对大鼠在体心肌缺血／再灌注损伤的保护作用

目的：研究雷米普利与BQ-123合用对大鼠在体心肌缺血／再灌注损伤的影响。方法：健康雄性Wistar大鼠随机分为5组,制备缺血30min再灌注120min模型,采用雷米普利、BQ-123单用及两药联合应用的方式处理实验动物。观察两药合用对大鼠在体心肌缺血／再灌注损伤的保护作用。观察动物心率、血压、心电图ST-段变化,记录缺血期室性心律失常;检测血浆CK及LDH活力;心肌HE染色和TIC染色,定性和定量检测心肌梗死情况。结果：与I／R组比较,各给药组ST-段均明显降低;缺血期室性心律失常（VA）出现时间明显推迟且持续时间明显缩短,联合给药组作用更为显著;心律失常发生率明显降低;血浆CK及LDH活力显著降低且联合给药组降低更为显著;梗死面积明显缩小,心肌损伤程度明显减轻,其中联合给药组变化更为显著。结论：雷米普利、BQ-123单用及联合应用均对大鼠在体心肌缺血／再灌注损伤有保护作用,且两药合用在推迟缺血期VA的出现时间,缩短其持续时间,减少CK及LDH漏出,缩小心肌梗死面积方面优于两药各自单用。     

Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth.

The role of bone marrow (BM)-derived precursor cells in tumor angiogenesis is not known. We demonstrate here that tumor angiogenesis is associated with recruitment of hematopoietic and circulating endothelial precursor cells (CEPs). We used the angiogenic defective, tumor resistant Id-mutant mice to show that transplantation of wild-type BM or vascular endothelial growth factor (VEGF)-mobilized stem cells restore tumor angiogenesis and growth. We detected donor-derived CEPs throughout the neovessels of tumors and Matrigel-plugs in an Id1+/-Id3-/- host, which were associated with VEGF-receptor-1-positive (VEGFR1+) myeloid cells. The angiogenic defect in Id-mutant mice was due to impaired VEGF-driven mobilization of VEGFR2+ CEPs and impaired proliferation and incorporation of VEGFR1+ cells. Although targeting of either VEGFR1 or VEGFR2 alone partially blocks the growth of tumors, inhibition of both VEGFR1 and VEGFR2 was necessary to completely ablate tumor growth. These data demonstrate that recruitment of VEGF-responsive BM-derived precursors is necessary and sufficient for tumor angiogenesis and suggest new clinical strategies to block tumor growth.     

Auxin increases the hydraulic conductivity of auxin-sensitive hypocotyl tissue

The ability of water to enter the cells of growing hypocotyl tissue was determined in etiolated soybean (Glycine max (L.) Merr.) seedlings. Water uptake was restricted to that for cell enlargement, and the seedlings were kept intact insofar as possible. Tissue water potentials ( _w) were measured at thermodynamic equilibrium with an isopiestic thermocouple psychrometer. _wwas below the water potential of the environment by as much as 3.1 bars when the tissue was enlarging rapidly. However, _w was similar to the water potential of the environment when cell enlargement was not occurring. The low _w in enlarging tissue indicates that there was a low conductivity for water entering the cells.The ability of water to enter the enlarging cells was defined as the apparent hydraulic conductivity of the tissue (Lp). Despite the low Lp of growing cells, Lp decreased further as cell enlargement decreased when intact hypocotyl tissue was deprived of endogenous auxin (indole-3-acetic acid) by removal of the hypocotyl hook. Cell enlargement resumed and Lp increased when auxin was resupplied exogenously. The auxin-induced increase in Lp was correlated with the magnitude of the growth enhancement caused by auxin, and it was observed during the earliest phase of the growth response to auxin. The increase in Lp appeared to be caused by an increase in the hydraulic conductivity of the cell protoplasm, since other factors contributing to Lp remained constant. The rapidity of the response is consistent with a cellular site of action at the plasmalemma, although other sites are not precluded.Because the experiments involved only short times, auxin-induced changes in cell enlargement could not be attributed to changes in cell osmotic potentials. Neither could they be attributed to changes in turgor, which increased when the rate of enlargement decreased. Rather, auxin appeared to act by altering the extensibility of the cell walls and by simultaneously altering the ability of water to enter the growing cells under a given water potential gradient. The hydraulic conductivity and extensibility of the cell walls appeared to contribute about equally to the control of the growth rate of the hypocotyls.     

Well-to-wheel GHG emissions and mitigation potential from light-duty vehicles in Macau

Purpose

The rapid growth of vehicle sales and usage has highlighted the need for greenhouse gas (GHG) emission reduction in Macau, a special administrative region (SAR) of China. As the most primary vehicle type, light-duty vehicles (LDV, including light-duty gasoline vehicles (LDGVs) and light-duty diesel vehicles (LDDVs)) play a key role in promoting the GHG reduction and development of green transportation system in Macau.

Methods

This study, on the basis of real-world tested and statistical data, firstly performed a streamlined life-cycle assessment (SLCA) on LDVs, to evaluate the potential GHG emissions and reduction through shifting to hybrid electric vehicles (HEVs) and electric vehicles (EVs).

Results and discussion

The results show that the mean GHG emissions from the LDGVs, LDDVs, and HEVs per 100 km were 25.16, 20.30, and 15.00 kg CO₂ eq, respectively. Under the current electricity mix in Macau, EVs with the emissions of 12.39 kg CO₂ eq/100 km can achieve a significant GHG emission reduction of LDVs in Macau. The total GHG emissions from LDVs increased from 124.99 to 247.82 thousand metric tons over the periods 2001–2014, with a 5.42% annual growth rate. A scenario analysis indicated that the development of HEVs and EVs—especially EVs—has the potential to control the GHG emissions from LDVs. Under the electricity mix of natural gas (NG) and solar energy (SE), the GHG emissions from EVs would drop by about 22 and 28%, respectively, by 2030.

Conclusions

This study develops a useful approach to evaluate the potential GHG emissions and its reduction strategies in Macau. All the obtained results could be useful for decision makers, providing robust support for drawing up an appropriate plan for improving green transportation systems in Macau.

     

GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export

Molecular mechanisms governing the anterograde trafficking of nascent G protein-coupled receptors (GPCRs) are poorly understood. Here, we have studied the regulation of cell surface transport of α₂-adrenergic receptors (α₂-ARs) by GGA3 (Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding protein 3), a multidomain clathrin adaptor protein that sorts cargo proteins at the trans-Golgi network (TGN) to the endosome/lysosome pathway. By using an inducible system, we demonstrated that GGA3 knockdown significantly inhibited the cell surface expression of newly synthesized α_2B-AR without altering overall receptor synthesis and internalization. The receptors were arrested in the TGN. Furthermore, GGA3 knockdown attenuated α_2B-AR-mediated signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) activation and cyclic AMP (cAMP) inhibition. More interestingly, GGA3 physically interacted with α_2B-AR, and the interaction sites were identified as the triple Arg motif in the third intracellular loop of the receptor and the acidic motif EDWE in the VHS domain of GGA3. In contrast, α_2A-AR did not interact with GGA3 and its cell surface export and signaling were not affected by GGA3 knockdown. These data reveal a novel function of GGA3 in export trafficking of a GPCR that is mediated via a specific interaction with the receptor.     

A novel RNA-binding mode of the YTH domain reveals the mechanism for recognition of determinant of selective removal by Mmi1

The YTH domain-containing protein Mmi1, together with other factors, constitutes the machinery used to selectively remove meiosis-specific mRNA during the vegetative growth of fission yeast. Mmi1 directs meiotic mRNAs to the nuclear exosome for degradation by recognizing their DSR (determinant of selective removal) motif. Here, we present the crystal structure of the Mmi1 YTH domain in the apo state and in complex with a DSR motif, demonstrating that the Mmi1 YTH domain selectively recognizes the DSR motif. Intriguingly, Mmi1 also contains a potential m⁶A (N⁶-methyladenine)-binding pocket, but its binding of the DSR motif is dependent on a long groove opposite the m⁶A pocket. The DSR-binding mode is distinct from the m⁶A RNA-binding mode utilized by other YTH domains. Furthermore, the m⁶A pocket cannot bind m⁶A RNA. Our structural and biochemical experiments uncover the mechanism of the YTH domain in binding the DSR motif and help to elucidate the function of Mmi1.