人类免疫缺陷病毒1／2型抗体检测酶联免疫试剂盒的研制

采用二聚体合成肽（ＨＩＶ－１ｇｐ４１、ｇｐ１２０、ｐ２４和ＨＩＶ－２ｇｐ３６）包被酶标板条制备成固相抗原,与鼠抗人ＩｇＧ单克隆抗体酶标记物、底物ＴＭＢ及阴阳性参考血清配套制备成ＨＩＶ抗体ＥＩＡ试剂盒,专供检测人血清或血浆ＨＩＶ１／２抗体之用。以荷兰、韩国及万泰试剂作为对照,用该试剂盒对检定所的Ｐａｎｅｌ标准及献血员１５５５０例（其中ＨＣＶ抗体阳性１２８例,ＨＢｓＡｇ阳性４６例）进行检测,四种试剂对检定所Ｐａｎｅｌ标准的１３份阳性血清均呈阳性反应,２８份阴性血清均为阴性;献血员１５５５０例,四种试剂对其中１份血清均呈阳性反应,经Ｗｅｓｔｅｒｎｂｌｏｔ试验证实为阴性,四种试剂的阴性检出率均为９９．９９％。连续制备三批试剂经中国药品生物制品检定所检定,所检项目全部合格;同时委托检定所进行临床考核,４７份阳性血清全部呈阳性反应,１５０份阴性血清全部为阴性。说明该试剂盒具有很好的敏感性和特异性。     

Suppression of Coronary Atherosclerosis by Helix B Surface Peptide,a Nonerythropoietic,Tissue-Protective Compound Derived from Erythropoietin

Erythropoietin (EPO), a type I cytokine originally identified for its critical role in hematopoiesis, has been shown to have nonhematopoietic, tissue-protective effects, including suppression of atherosclerosis. However, prothrombotic effects of EPO hinder its potential clinical use in nonanemic patients. In the present study, we investigated the antiatherosclerotic effects of helix B surface peptide (HBSP), a nonerythropoietic, tissue-protective compound derived from EPO, by using human umbilical vein endothelial cells (HUVECs) and human monocytic THP-1 cells in vitro and Watanabe heritable hyperlipidemic spontaneous myocardial infarction (WHHLMI) rabbits in vivo. In HUVECs, HBSP inhibited apoptosis (≈70%) induced by C-reactive protein (CRP), a direct mediator of atherosclerosis. By using a small interfering RNA approach, Akt was shown to be a key molecule in HBSP-mediated prevention of apoptosis. HBSP also attenuated CRP-induced production of tumor necrosis factor (TNF)-α and matrix metalloproteinase-9 in THP-1 cells. In the WHHLMI rabbit, HBSP significantly suppressed progression of coronary atherosclerotic lesions as assessed by mean cross-sectional stenosis (HBSP 21.3 ± 2.2% versus control peptide 38.0 ± 2.7%) and inhibited coronary artery endothelial cell apoptosis with increased activation of Akt. Furthermore, TNF-α expression and the number of M1 macrophages and M1/M2 macrophage ratio in coronary atherosclerotic lesions were markedly reduced in HBSP-treated animals. In conclusion, these data demonstrate that HBSP suppresses coronary atherosclerosis, in part by inhibiting endothelial cell apoptosis through activation of Akt and in association with decreased TNF-α production and modified macrophage polarization in coronary atherosclerotic lesions. Because HBSP does not have the prothrombotic effects of EPO, our study may provide a novel therapeutic strategy that prevents progression of coronary artery disease.     

Hydroxyl-Functionalized DNAs with Different Linkers and Their Complmentary Duplex Stability

Tert-butyldiphenylsilyl (TBDPS) was testified to be an appropriate orthogonal protecting group for novel 7-hydroxyl-functionalized 8-aza-7-deaza-2′-deoxyadenosine analogues. It was stable in partial and complete hydrogenation reactions used for the different linker preparation. The corresponding phosphoramidites and hydroxyl-functionalized oligodeoxynucleotides were synthesized and identified. The thermal effect of the hydroxyl group with different linkers on DNA duplexes was evaluated. It provided a feasible strategy for the preparation of hydroxyl-functionalized DNAs for the nucleic acid research.     

Costs of Inaction on Maternal Mortality: Qualitative Evidence of the Impacts of Maternal Deaths on Living Children in Tanzania

Background

Little is known about the interconnectedness of maternal deaths and impacts on children, beyond infants, or the mechanisms through which this interconnectedness is established. A study was conducted in rural Tanzania to provide qualitative insight regarding how maternal mortality affects index as well as other living children and to identify shared structural and social factors that foster high levels of maternal mortality and child vulnerabilities.

Methods and Findings

Adult family members of women who died due to maternal causes (N = 45) and key stakeholders (N = 35) participated in in-depth interviews. Twelve focus group discussions were also conducted (N = 83) among community leaders in three rural regions of Tanzania. Findings highlight the widespread impact of a woman’s death on her children’s health, education, and economic status, and, by inference, the roles that women play within their families in rural Tanzanian communities.

Conclusions

The full costs of failing to address preventable maternal mortality include intergenerational impacts on the nutritional status, health, and education of children, as well as the economic capacity of families. When setting priorities in a resource-poor, high maternal mortality country, such as Tanzania, the far-reaching effects that reducing maternal deaths can have on families and communities, as well as women’s own lives, should be considered.     

New Anthracene‐Fused Nonfullerene Acceptors for High‐Efficiency Organic Solar Cells: Energy Level Modulations Enabling Match of Donor and Acceptor

Two new nonfullerene small molecule acceptors (NF‐SMAs) AT‐NC and AT‐4Cl based on heptacyclic anthracene(cyclopentadithiophene) (AT) core and different electron‐withdrawing end groups are designed and synthesized. Although the two new acceptor molecules use two different end groups, naphthyl‐fused indanone (NINCN) and chlorinated INCN (INCN‐2Cl) demonstrate similar light absorption. AT‐4Cl with chlorinated INCN as end groups are shifted significantly due to the strong electron‐withdrawing ability of chlorine atoms. Thus, desirable V_oc and photovoltaic performance are expected to be achieved when polymer PBDB‐T is used as the electron donor with AT‐NC as the acceptor, and fluorinated analog PBDB‐TF with down‐shifted energy levels is selected to blend with AT‐4Cl. Consequently, the device based on PBDB‐TF:AT‐4Cl yields a high power conversion efficiency of 13.27% with a slightly lower V_oc of 0.901 V, significantly enhanced J_sc of 19.52 mA cm^?2 and fill factor of 75.5% relative to the values based on PBDB‐T:AT‐NC. These results demonstrate that the use of a new electron‐rich AT core, together with energy levels modulations by end‐group optimizations enabling the match with polymer donors, is a successful strategy to construct high‐performance NF‐SMAs.     

Ecological application of wavelet analysis in the scaling of spatial distribution patterns of Ceratoides ewersmanniana

Ecological experiments are usually conducted on small scales, but the ecological and environmental issues are usually on large scales. Hence, there is a clear need of scaling. Namely, when we deal with patterns and processes on larger scales, a special connection needs to be established on the small scales that we are familiar with. Here we presented a wavelet analysis method that could build relationships between spatial distribution patterns on different scales. With this method, we also studied how spatial heterogeneity and distribution patterns changed with the scale. We investigated the distribution and the habitat of C. ewersmanniana in two plots (200 m × 200 m; the distance between these two plots is 15 km) at Mosuowan desert. The results demonstrated that spatial heterogeneity and distribution patterns were incorporated into larger scales when the wavelet scale varied from one (5 m) to four (20 m). However, if the wavelet scale was above five (25 m), the spatial distribution patterns varied placidly, the oscillation frequency of landforms stabilized at 110 m, and the dynamic quantity period of C. ewersmanniana stabilized at 115–125 m. We also identified signal mutation points with wavelet analysis and verified the heterogeneity degree of local space with position variance. We found that position variance decomposed the distribution patterns on large scales into small sampling plots, and the position with the largest variance also had the strongest heterogeneity. In a word, the wavelet analysis method could scale-up spatial distribution patterns and habitat heterogeneity. With this method and other methods derived from this one, such as wavelet scale, wavelet variance, position variance and extremely direct-viewing graphs, wavelet analysis could be widely applied in solving the scaling problem in ecological and environmental studies.     

Long noncoding RNA CPS1-IT1 suppresses melanoma cell metastasis through inhibiting Cyr61 via competitively binding to BRG1

Long noncoding RNA CPS1-IT1 is recently recognized as a tumor suppressor in several cancers. Here, we investigate the role of CPS1-IT1 in human melanoma. Presently, our study reveals the low expression of CPS1-IT1 in human melanoma tissues and cell lines, which is significantly associated with metastasis and tumor stage. Besides, the potential of CPS1-IT1 as a prognosis-predictor is strongly indicated. Functionally, CPS1-IT1 overexpression inhibits cell migration, invasion, epithelial–mesenchymal transition, and angiogenesis in melanoma cells. CYR61, an angiogenic factor that participates in tumor metastasis as well as a recognized oncogene in melanoma, is shown to be confined under CPS1-IT1 overexpression in melanoma cells. Furthermore, enforced expression of Cyr61 in CPS1-IT1-silenced melanoma cells dramatically normalized the protein level of Cyr61 and that of its downstream targets vascular endothelial growth factor and matrix metalloproteinase-9, as well as the repressive effect of CPS1-IT1 overexpression on melanoma cell metastasis. BRG1, a core component of SWI/SNF complex, is implied to interact with both CPS1-IT1 and Cyr61 in melanoma cells. Moreover, CPS1-IT1 negatively regulates Cyr61 expression by blocking the binding of BRG1 to Cyr61 promoter. Jointly, CPS1-IT1 controls melanoma metastasis through impairing Cyr61 expression via competitively binding with BRG1, uncovering a novel potential therapeutic and prognostic biomarker for patients with melanoma.     

TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination

Expression of the E3 ligase TRIM21 is increased in a broad spectrum of cancers; however, the functionally relevant molecular pathway targeted by TRIM21 overexpression remains largely unknown. Here, we show that TRIM21 directly interacts with and ubiquitinates CLASPIN, a mediator for ATR-dependent CHK1 activation. TRIM21-mediated K63-linked ubiquitination of CLASPIN counteracts the K6-linked ubiquitination of CLASPIN which is essential for its interaction with TIPIN and subsequent chromatin loading. We further show that overexpression of TRIM21, but not a TRIM21 catalytically inactive mutant, compromises CHK1 activation, leading to replication fork instability and tumorigenesis. Our findings demonstrate that TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination, providing a potential target for cancer therapy.     

Harnessing Case Isolation and Ring Vaccination to Control Ebola

As a devastating Ebola outbreak in West Africa continues, non-pharmaceutical control measures including contact tracing, quarantine, and case isolation are being implemented. In addition, public health agencies are scaling up efforts to test and deploy candidate vaccines. Given the experimental nature and limited initial supplies of vaccines, a mass vaccination campaign might not be feasible. However, ring vaccination of likely case contacts could provide an effective alternative in distributing the vaccine. To evaluate ring vaccination as a strategy for eliminating Ebola, we developed a pair approximation model of Ebola transmission, parameterized by confirmed incidence data from June 2014 to January 2015 in Liberia and Sierra Leone. Our results suggest that if a combined intervention of case isolation and ring vaccination had been initiated in the early fall of 2014, up to an additional 126 cases in Liberia and 560 cases in Sierra Leone could have been averted beyond case isolation alone. The marginal benefit of ring vaccination is predicted to be greatest in settings where there are more contacts per individual, greater clustering among individuals, when contact tracing has low efficacy or vaccination confers post-exposure protection. In such settings, ring vaccination can avert up to an additional 8% of Ebola cases. Accordingly, ring vaccination is predicted to offer a moderately beneficial supplement to ongoing non-pharmaceutical Ebola control efforts.     

Evolutionary change in testes tissue composition among experimental populations of house mice

Theory assumes that postcopulatory sexual selection favors increased investment in testes size because greater numbers of sperm within the ejaculate increase the chance of success in sperm competition, and larger testes are able to produce more sperm. However, changes in the organization of the testes tissue may also affect sperm production rates. Indeed, recent comparative analyses suggest that sperm competition selects for greater proportions of sperm‐producing tissue within the testes. Here, we explicitly test this hypothesis using the powerful technique of experimental evolution. We allowed house mice (Mus domesticus) to evolve via monogamy or polygamy in six replicate populations across 24 generations. We then used histology and image analysis to quantify the proportion of sperm‐producing tissue (seminiferous tubules) within the testes of males. Our results show that males that had evolved with sperm competition had testes with a higher proportion of seminiferous tubules compared with males that had evolved under monogamy. Previously, it had been shown that males from the polygamous populations produced greater numbers of sperm in the absence of changes in testes size. We thus provide evidence that sperm competition selects for an increase in the density of sperm‐producing tissue, and consequently increased testicular efficiency.