Is Order the Defining Feature of Magnitude Representation? An ERP Study on Learning Numerical Magnitude and Spatial Order of Artificial Symbols

Using an artificial-number learning paradigm and the ERP technique, the present study investigated neural mechanisms involved in the learning of magnitude and spatial order. 54 college students were divided into 2 groups matched in age, gender, and school major. One group was asked to learn the associations between magnitude (dot patterns) and the meaningless Gibson symbols, and the other group learned the associations between spatial order (horizontal positions on the screen) and the same set of symbols. Results revealed differentiated neural mechanisms underlying the learning processes of symbolic magnitude and spatial order. Compared to magnitude learning, spatial-order learning showed a later and reversed distance effect. Furthermore, an analysis of the order-priming effect showed that order was not inherent to the learning of magnitude. Results of this study showed a dissociation between magnitude and order, which supports the numerosity code hypothesis of mental representations of magnitude.     

Circulating MiR-125b as a marker predicting chemoresistance in breast cancer

Background

Chemotherapy is an important component in the treatment paradigm for breast cancers. However, the resistance of cancer cells to chemotherapeutic agents frequently results in the subsequent recurrence and metastasis. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of circulating microRNAs (miRNAs) can predict clinical outcome in breast cancer patients treated with adjuvant chemotherapy.

Methodology/Principal Findings

Circulating miRNAs in blood serum prior to treatment were determined by quantitative Real-Time PCR in 56 breast cancer patients with invasive ductal carcinoma and pre-operative neoadjuvant chemotherapy. Proliferating cell nuclear antigen (PCNA) immunostaining and TUNEL were performed in surgical samples to determine the effects of chemotherapy on cancer cell proliferation and apoptosis, respectively. Among the miRNAs tested, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression level in non-responsive patients (n = 26, 46%; p = 0.008). In addition, breast cancers with high miR-125b expression had higher percentage of proliferating cells and lower percentage of apoptotic cells in the corresponding surgical specimens obtained after neoadjuvant chemotherapy. Increased resistance to anticancer drug was observed in vitro in breast cancer cells with ectopic miR-125b expression; conversely, reducing miR-125b level sensitized breast cancer cells to chemotherapy. Moreover, we demonstrated that the E2F3 was a direct target of miR-125b in breast cancer cells.

Conclusions/Significance

These data suggest that circulating miR-125b expression is associated with chemotherapeutic resistance of breast cancer. This finding has important implications in the development of targeted therapeutics for overcoming chemotherapeutic resistance in novel anti-cancer strategies.     

Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.     

Vicilin Genes of Vigna luteola: Structure, Organization, Expression, and Variation

Two different but related sequences that encode Vigna luteola 7S vicilins were isolated and characterized. The sequences differ by two nucleotide substitutions, each of which results in an amino acid replacement. This low level of divergence suggests that a recent gene duplication has occurred. Both variants are expressed in cDNA populations; therefore, neither gene is a pseudogene. Both copies were present in all individuals (72) analyzed using real-time PCR and TaqMan probes. Segregation was not observed. The two sequences are not independent alleles. Vicilin genomic sequences of 11 specimens from six geographic locations were determined. No polymorphic sites were identified in either of the two gene copies. This lack of polymorphism suggests that either a population bottleneck or selection has occurred. The genetic structure, expression patterns, and protein composition of the V. luteola vicilins were compared to those of other legume vicilins.     

Identification and characterization of fully human anti-CD22 monoclonal antibodies

CD22 is a member of the B cell receptor family and is implicated in B cell function and development. It is expressed on multiple forms of B cell lymphoma and is an attractive cancer therapeutic target. We report here the identification of two fully human anti-CD22 antibodies using phage display methodology. Both antibodies exhibit specific binding to cell surface-associated CD22 in multiple B cell lines. Through ELISA using mammalian cell-expressed sub-domains of CD22 as binding antigen, we mapped the binding epitopes of the newly identified CD22 antibodies to be within the Ig-like domains 5 to 7 of CD22. Their epitopes do not overlap with those of several therapeutic antibodies currently in preclinical or clinical development. These antibodies have potential as cancer therapeutic candidates and research reagents.Key words: human antibody, CD22, phage display, cancer, hematological     

深圳大鹏半岛薇甘菊的空间发生规律

【目的】研究薇甘菊的入侵与地形、人为干扰间的关系,量化不同干扰因素对薇甘菊发生的影响,进一步揭示薇甘菊的发生规律,为薇甘菊的系统防治与管控提供技术支持。【方法】使用无人机遥感系统所获取的高分辨率航片作为数据源,通过目视解译方法确定薇甘菊的发生区域后结合3S技术手段,对深圳大鹏半岛210000 m²研究区内的薇甘菊发生状况与地形因子及人为干扰度间的关系进行系统分析。【结果】研究区内薇甘菊在低海拔区和阳坡分布居多,86.80%的薇甘菊入侵发生在人类轻中度干扰区,20°~40°坡度位置是薇甘菊的重点发生区。研究网格单元内薇甘菊的发生面积与坡度、高程显著负相关(P<0.01),与坡向相关性较差。【结论】在人为干扰较小的自然条件下,制约薇甘菊扩散发生的主要因子是入侵地的群落结构,而在人为干扰较为严重的地区,薇甘菊入侵的发生与人类活动消失后产生的空白生态位密切相关。     

Differential killing of CD56-expressing cells by drug-conjugated human antibodies targeting membrane-distal and membrane-proximal non-overlapping epitopes

CD56 (NCAM, neural cell adhesion molecule) is over-expressed in many tumor types, including neuroblastoma, multiple myeloma, small cell lung cancer, ovarian cancer, acute myeloid leukemia, NK-T lymphoma, neuroendocrine cancer and pancreatic cancer. Using phage display, we identified 2 high-affinity anti-CD56 human monoclonal antibodies (mAbs), m900 and m906, which bound to spatially separated non-overlapping epitopes with similar affinity (equilibrium dissociation constant 2.9 and 4.5 nM, respectively). m900 bound to the membrane proximal fibronectin type III-like domains, whereas m906 bound to the N-terminal IgG-like domains. m906 induced significant down-regulation of CD56 in 4 neuroblastoma cell lines tested, while m900-induced downregulation of CD56 was much lower. Antibody-drug conjugates (ADCs) made by conjugation with a highly potent pyrrolobenzodiazepine dimer (PBD) exhibited killing activity that correlated with CD56 down-regulation, and to some extent with in vivo binding ability of the antibodies. The m906PBD ADC was much more potent than m900PBD, likely due to higher CD56-mediated downregulation and stronger binding to cells. Treatment with m906PBD ADC resulted in very potent cytotoxicity (IC50: 0.05–1.7 pM). These results suggest a novel approach for targeting CD56-expressing neuroblastoma cells. Further studies in animal models and in humans are needed to find whether these antibodies and their drug conjugates are promising candidate therapeutics.     

我国胶园间作的回顾与展望

胶园间作通常指在胶园中间种农作物或其他经济作物，以收获间作物产品为主要目的的生产过程。在橡胶园，橡胶树按照人的意愿，即以“理想”的种植密度和种植形式栽植，因而在橡胶园里，尤其在幼龄胶园中，尚有部分未被利用的资源，这是胶园间作的基础。胶园种植豆科覆盖作...     

盐旱复合胁迫对小麦幼苗生长和水分吸收的影响

为明确盐害、干旱及盐旱复合胁迫对小麦幼苗生长和水分吸收的影响,从而为盐害和干旱胁迫下栽培调控提供理论依据。以2个抗旱性不同的小麦品种(扬麦16和耐旱型洛旱7号)为材料,采用水培试验,以NaCl和PEG模拟盐旱复合胁迫,研究了盐旱复合胁迫下小麦幼苗生长、根系形态、光合特性及水分吸收特性的变化。结果表明,盐、旱及复合胁迫下小麦幼苗的生物量、叶面积、总根长与根系表面积、叶绿素荧光和净光合速率均显著下降,但是复合胁迫处理的降幅却显著低于单一胁迫。盐旱复合胁迫下根系水导速率和根系伤流液强度显著大于单一胁迫,从而提高了小麦幼苗叶片水势和相对含水量。盐胁迫下小麦幼苗Na~+/K~+显著大于复合胁迫,但复合胁迫下ABA含量却显著小于单一的盐害和干旱胁迫。因此,盐旱复合胁迫可以通过增强根系水分吸收及降低根叶中ABA含量以维持较高光合能力,这是盐旱复合胁迫提高小麦适应性的重要原因。洛旱7号和扬麦16对盐及盐旱复合胁迫的响应基本一致,但在干旱胁迫下洛旱7号表现出明显的耐性。