每年，性别差异的组织（OSSD）和主编性别差异的生物学选择一份在该日历年内发表的杰出论文，并在年度会议期间向作者颁发OSSD-BSD出版奖。今年的赢家是乔安娜·弗洛洛斯（Joanna Floros）博士。该博客由Floros博士及其同事撰写，概述了她的开始是性别差异研究人员和屡获殊荣论文的结果。

A sex differences researcher is born
在我的博士后培训之后，我（Joanna Floros博士）开始与哈佛医学院儿科学系的新生儿学临床组合作。该研究重点是肺表面活性剂，肺表面活性剂是一种脂蛋白复合物，这对生命至关重要，因为它降低了表面张力并防止肺塌陷。缺乏肺表面活性剂或不足的表面活性剂的过早出生的婴儿呼吸问题，并且可能患上呼吸窘迫综合征（RDS）。过早出生的雄性婴儿患RDS的风险较高，因为表面活性剂的产生有些延迟。因此，从我从事肺部研究的一开始，我就意识到性是我的研究中要考虑的重要变量。

To this day, pulmonary surfactant proteins remain the primary focus of my lab. These proteins (particularly the protein “SP-A,” which stands for surfactant protein A) along with the alveolar macrophage (“AM,” also known as dust cells for the role they play in ‘cleaning’ the lungs of potentially harmful particles), are the first line of defense against a number of harmful pathogens, allergens, and pollutants, such as ozone (O₃). In humans the SP-A chromosomal locus consists of two functional genes, which encode the SP-A1 and SP-A2 proteins, respectively. Each gene was further identified with several SP-A-based variants that differ within the coding sequence. Genetic studies showed that these SP-A1 and SP-A2 variants associate with various pulmonary diseases, and体外研究表明，两个基因产物和变体之间的功能，结构和调节差异。目前，我们必须研究这些变体体内这导致了人源化转基因（HTG）小鼠的创建，其中每只小鼠携带一个不同的人类SP-A变体，并且编码SP-A变体的基因被淘汰（KO）。

2017年OSSD-BSD出版奖论文：研究摘要
环境污染（尤其是O₃-induced oxidative stress) not only negatively affects lung function and inflammation, but differentially affects SP-A variants. We and others have shown that in the absence of SP-A, the negative effects of pneumonia and other types of lung injury increase. Moreover, sex differences have been observed in the survival rates between male and female wild type and SP-A KO mice after bacterial infection alone or preceded by O₃- 诱导的氧化应激。女性仅在感染中就表现出更好的存活率，但是当氧化应激先于感染之前，雄性的生存结果逆转了。显然，性激素在这种结果中起着作用，因为未观察到频率很高的散发/绝育小鼠生存的性别差异。还观察到AM蛋白质组中的性别差异是SP-A基因型的函数。因为SPA通过通过AM和炎症过程调节病原体（包括细菌）的去除（包括细菌），在肺的先天免疫中起关键作用，这两种过程都是几种肺部疾病的核心，我们在我们的研究中寻求研究机制O的影响₃-induced oxidative stress on the regulation of the AM miRNome as a function of SP-A genotype and sex.

我们假设在存在或不存在氧化应激的情况下，两个人类SP-A1和SP-A2基因产物在雄性和雌性小鼠中差异调节AM miRNOME。microRNA（miRNA）是参与基因转录后调节的简短非编码RNA，并在多种生物过程中起关键作用。在哺乳动物细胞中已经鉴定出许多miRNA，并且所有蛋白质编码基因的三分之一受这些小分子调节。

我们将表达SP-A1或SP-A2的雄性和雌性小鼠暴露于O₃或过滤空气（对照），并测量372 miRNA的表达水平。鉴定出对氧化应激的反应显着改变的miRNA，并用于鉴定涉及的途径和分子，并可能受这些miRNA的影响。研究结果表明，AM miRNOME受两个SP-A基因的差异调节，以响应O₃exposure and that the SP-A2 male (but not female) miRNome is associated with genes involved in inflammation pathways, regulation of reactive oxygen species, and cell death (summarized in Figure 1), indicating that the pathways involved are sex-specific. The involvement of sex hormones in the SP-A2 sex-specific miRNome findings was supported by our findings in spayed and neutered mice where the regulation of the miRNome of the SP-A2 male mice compared to that of female mice in response to oxidative stress was significantly altered after castration. These findings support previous observations of sex differences in survival.

Even though both males and females have similar respiratory requirements, sex has been identified as one of the several risk factors for lung disease identified in humans. Sexual dimorphism in lung function can significantly influence the clinical outcome and modulate lung disease susceptibility, as is the case in respiratory infections, COPD, asthma, and CF, and in asthma exacerbations in response to O₃exposure.

结果本研究提供有关可能发生某些性别差异的机制的见解。将来，此信息可能有助于考虑适当的性别特异性治疗疗法和/或避免一种性别与另一种性别的负面副作用，甚至可能完全触发甚至完全缺乏男性与女性的药物或疗法的疗效反之亦然。此外，不管性研究是否涉及动物还是人类，并非所有动物/人类都有相同的临床结果，表明其他因素也会促进。在本研究中，我们观察到SP-A遗传学在O之后的结果中起着重要作用₃- 诱导的氧化应激。这很重要，因为为了进步，我们需要考虑一些包括性别，遗传学和环境影响在内的许多因素。