Targeted therapy for gastric cancer: Molecular pathways and ongoing investigations

Gastric cancer is currently the second leading cause of worldwide cancer mortality. Ongoing collaborative sequencing efforts have highlighted recurrent somatic genomic aberrations in gastric cancer, however, despite advances in characterizing the genomic landscape, there have been few advances in patient outcomes. Prognosis remains poor with a median overall survival of 12 months for advanced disease. The improved survival with trastuzumab, and more recently ramucirumab, underscore the promise of targeted and biologic therapies and the importance of molecular tumor characterization in gastric cancer. Here we review the most frequent actionable alterations in gastric cancer and highlight ongoing clinical investigations attempting to translate biologic understanding into improved clinical outcomes.     

Increased expression of mdig predicts poorer survival of the breast cancer patients

Breast cancer is the most common cancer and the second leading cause of cancer death among women of all races and Hispanic origin populations in the United States. In the present study, we reported that the survival time of the breast cancer patients is influenced by the expression level of mdig, a previously identified lung cancer-associated oncogene encoding a JmjC-domain protein. By checking the expression levels of mRNA and protein of mdig through both RT-PCR and immunohistochemistry in samples from 204 patients, we noticed that about 30% of breast cancer samples showed increased expression of mdig. Correlation of the mdig expression levels with the survival time of the breast cancer patients indicated a clear inverse relationship between mdig expression and patient survival, including poorer overall survival, distant metastasis free survival, relapse free survival, and post-progression survival. Taken together, these data suggest that an increased expression of mdig is an important prognostic factor for poorer survival time of the breast cancer patients.     

Positive interactions between herbivores and plant diversity shape forest regeneration

The effects of herbivores and diversity on plant communities have been studied separately but rarely in combination. We conducted two concurrent experiments over 3 years to examine how tree seedling diversity, density and herbivory affected forest regeneration. One experiment factorially manipulated plant diversity (one versus 15 species) and the presence/absence of deer (Odocoileus virginianus). We found that mixtures outperformed monocultures only in the presence of deer. Selective browsing on competitive dominants and associational protection from less palatable species appear responsible for this herbivore-driven diversity effect. The other experiment manipulated monospecific plant density and found little evidence for negative density dependence. Combined, these experiments suggest that the higher performance in mixture was owing to the acquisition of positive interspecific interactions rather than the loss of negative intraspecific interactions. Overall, we emphasize that realistic predictions about the consequences of changing biodiversity will require a deeper understanding of the interaction between plant diversity and higher trophic levels. If we had manipulated only plant diversity, we would have missed an important positive interaction across trophic levels: diverse seedling communities better resist herbivores, and herbivores help to maintain seedling diversity.     

Paternal care in a fish: epigenetics and fitness enhancing effects on offspring anxiety

In many animals, including humans, interactions with caring parents can have long-lasting effects on offspring sensitivity to stressors. However, whether these parental effects impact offspring fitness in nature is often unclear. In addition, despite evidence that maternal care can influence offspring behaviour via epigenetic alterations to the genome, it remains unclear whether paternal care has similar effects. Here, we show in three-spined sticklebacks, a fish in which fathers are the sole provider of offspring care, that the direct care provided by fathers affects offspring anxiety and the potential for epigenetic alterations to the offspring genome. We find that families are differentially vulnerable to early stress and fathers can compensate for this differential sensitivity with the quality of their care. This variation in paternal care is also linked to the expression in offspring brains of a DNA methyltransferase (Dnmt3a) responsible for de novo methylation. We show that these paternal effects are potentially adaptive and anxious offspring are unlikely to survive an encounter with a predator. By supplying offspring care, fathers reduce offspring anxiety thereby increasing the survival of their offspring—not in the traditional sense through resource provisioning but through an epigenetic effect on offspring behavioural development.     

荒漠绿洲过渡带沙拐枣种群结构及动态特征

沙拐枣(Calligonum mongolicum)作为黑河中游荒漠绿洲过渡带的一种主要固沙植物种,它对于维护荒漠绿洲过渡带生态系统的稳定性起到了至关重要的作用。通过样地调查和数据统计,绘制了沙拐枣种群的径级结构图,在此基础上编制了种群的特定时间生命表,分析了存活曲线、死亡率曲线等重要参数,并运用时间序列模型预测种群数量动态,以揭示荒漠绿洲过渡带沙拐枣种群的结构及动态特征。结果表明:沙拐枣种群属于增长型,Vpi'=0.0233,表明该种群趋近于稳定型,但沙拐枣种群Ⅰ、Ⅱ龄级个体数目少于Ⅲ龄级的个体数目;存活曲线趋于Deevey-Ⅱ,各龄级种群有相近的死亡率;时间序列预测分析表明,在未来2、4、6、8个龄级时间后沙拐枣老龄个体逐渐增多,幼龄株数则有所降低,种群稳定性长期维持困难,因此,适当的人工辅助恢复和现有植株及生境的保护是保持沙拐枣种群自然更新和种群恢复的关键。     

温度对褐飞虱发育、存活和产卵影响的关系模型

设置系列恒温19、22、25、28、31、34℃,测定了温度对褐飞虱发育、存活和产卵的影响,建立了温度对褐飞虱生物学参数影响的关系模型。试验结果表明:(1)褐飞虱卵和若虫的发育历期在28℃下最短。除22℃以外,短翅型雌若虫的发育历期长于雄若虫的发育历期。(2)34℃下,褐飞虱卵未成功孵化,推测34℃是褐飞虱发育的限制性高温。不同温度下若虫的存活率为:25℃22℃28℃19℃31℃;低温主要导致低龄若虫死亡,而高温则主要导致高龄若虫死亡。(3)不同温度下产卵前期为19℃31℃22℃25℃28℃。产卵期22℃时最长。短翅型雌虫寿命随着温度降低而延长,产卵量在28℃时最大(256粒),19℃时最低(108粒)。(4)采用温度(x)与褐飞虱各生物学参数(y)间进行回归分析,获得一系列关系模型;其中,卵历期(y=0.079 x2-4.462 x+70.536),若虫历期(y=0.233 x2-12.886 x+189.878),产卵前期(y=0.068 x2-3.614 x+49.88)和短翅型雌成虫寿命(y=-0.622 x+35.03)与温度间具有显著的回归关系。     

不同红小豆品种幼苗对干旱胁迫的生理响应

为筛选红小豆（Phaseolus angularis Linn.）幼苗抗旱性鉴定指标,采用盆栽控水方法,对红小豆3个品种‘保红947’、‘东北大红袍’、‘晋小豆5号’进行了苗期形态特征及根系生理生化特性的研究。结果表明：干旱胁迫抑制了红小豆3个品种植株的生长;重度干旱胁迫下,3个品种光系统Ⅱ（PSⅡ）的潜在活性（可变荧光/初始荧光,Fv/Fo）、最大光化学效率（可变荧光/最大荧光产量,Fv/Fm）、株高、叶面积、茎粗、根鲜重、根系活力、可溶性蛋白质含量等指标均随干旱胁迫强度的增加呈明显下降趋势,根冠比、根系脯氨酸（Pro）含量、可溶性糖含量、SOD活性、POD活性、MDA含量等指标随着干旱胁迫强度的增加呈明显上升趋势。综合各项生理指标,‘东北大红袍’在干旱胁迫下能保持相对较优的生理状态,抗旱性最强。通过主成分分析表明,株高、叶面积、茎粗、主根长、根鲜重、最大光化学效率、根系活力、可溶性糖含量、可溶性蛋白质含量、SOD活性、MDA含量等生理生化特性可作为鉴定红小豆苗期抗旱性的指标。