Protein domain definition should allow for conditional disorder

Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.     

A novel parasitoid and a declining butterfly: cause or coincidence?

1. The small tortoiseshell butterfly (Aglais urticae L.) is considered to be a widespread and abundant generalist species in Northern Europe. However, it declined sharply in the U.K. between 2003 and 2008, coinciding with the arrival and spread of a parasitoid, Sturmia bella Meig. (Diptera: Tachinidae), which specialises on nymphalid butterflies. 2. Whether the decline in A. urticae is associated with the arrival of S. bella was investigated using data from a large‐scale butterfly monitoring scheme, and by collecting larvae to assess parasitoid incidence and parasitism frequency. Similar data were compiled for a related butterfly (Inachis io) which is also parasitised by S. bella but which is not declining. 3. Sturmia bella was recorded as far north as north Lincolnshire (53.53°N). Aglais urticae has declined significantly to the south of this latitude, but not to the north. 4. Sturmia bella was present in 26% and 15% of the larval groups of A. urticae and I. io, respectively, and now kills more individuals of A. urticae (but not I. io) than any native parasitoid. 5. Survival was 25–48% lower in batches of A. urticae larvae where S. bella was present, indicating that S. bella causes host mortality in addition to that caused by native parasitoids. 6. Our results suggest that S. bella may be playing a role in the recent decline of A. urticae. However, further research is needed to establish its effects relative to other potential drivers of trends in the abundance of this butterfly.     

Guaiane- and aristolane-type sesquiterpenoids of Nardostachys chinensis roots

Two guaiane-type compounds, nardoguaianone J and K (1 and 2) and two aristolane-type compounds, kanshone F and G (3 and 4), were isolated from Nardostachys chinensis roots. The structures including the absolute configurations were elucidated by spectral means and by comparison of their CD spectra.     

Discriminating the effects of phylogenetic hypothesis,tree resolution and clade age estimates on phylogenetic signal measurements

Understanding how species traits evolved over time is the central question to comprehend assembly rules that govern the phylogenetic structure of communities. The measurement of phylogenetic signal (PS) in ecologically relevant traits is a first step to understand phylogenetically structured community patterns. The different methods available to estimate PS make it difficult to choose which is most appropriate. Furthermore, alternative phylogenetic tree hypotheses, node resolution and clade age estimates might influence PS measurements. In this study, we evaluated to what extent these parameters affect different methods of PS analysis, and discuss advantages and disadvantages when selecting which method to use. We measured fruit/seed traits and flowering/fruiting phenology of endozoochoric species occurring in Southern Brazilian Araucaria forests and evaluated their PS using Mantel regressions, phylogenetic eigenvector regressions (PVR) and K statistic. Mantel regressions always gave less significant results compared to PVR and K statistic in all combinations of phylogenetic trees constructed. Moreover, a better phylogenetic resolution affected PS, independently of the method used to estimate it. Morphological seed traits tended to show higher PS than diaspores traits, while PS in flowering/fruiting phenology depended mostly on the method used to estimate it. This study demonstrates that different PS estimates are obtained depending on the chosen method and the phylogenetic tree resolution. This finding has implications for inferences on phylogenetic niche conservatism or ecological processes determining phylogenetic community structure.     

Characterization of H3.3K36M as a tool to study H3K36 methylation in cancer cells

Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells. Here we show that expression of H3.3K36M in HT1080 fibrosarcoma cancer cells severely impairs cellular proliferation, which contrasts its role in promoting transformation of chondrocytic cells. H3.3K36M-associated cellular toxicity phenocopies the specific depletion of H3K36me2, but not loss of H3K36me3. We further find that the H3K36me2-associated toxicity is largely independent of changes in H3K27me3. Together, our findings lend support to the argument that H3K36me2 has distinct roles in cancer cells independent of H3K36me3 and H3K27me3, and highlight the use of H3.3K36M as an epigenetic tool to study H3K36 and H3K27 methylation dynamics in diverse cell types.     

Conserved insulin signaling in the regulation of oocyte growth,development, and maturation

Insulin signaling regulates various aspects of physiology, such as glucose homeostasis and aging, and is a key determinant of female reproduction in metazoans. That insulin signaling is crucial for female reproductive health is clear from clinical data linking hyperinsulinemic and hypoinsulinemic condition with certain types of ovarian dysfunction, such as altered steroidogenesis, polycystic ovary syndrome, and infertility. Thus, understanding the signaling mechanisms that underlie the control of insulin‐mediated ovarian development is important for the accurate diagnosis of and intervention for female infertility. Studies of invertebrate and vertebrate model systems have revealed the molecular determinants that transduce insulin signaling as well as which biological processes are regulated by the insulin‐signaling pathway. The molecular determinants of the insulin‐signaling pathway, from the insulin receptor to its downstream signaling components, are structurally and functionally conserved across evolution, from worms to mammals—yet, physiological differences in signaling still exist. Insulin signaling acts cooperatively with gonadotropins in mammals and lower vertebrates to mediate various aspects of ovarian development, mainly owing to evolution of the endocrine system in vertebrates. In contrast, insulin signaling in Drosophila and Caenorhabditis elegans directly regulates oocyte growth and maturation. In this review, we compare and contrast insulin‐mediated regulation of ovarian functions in mammals, lower vertebrates, C. elegans, and Drosophila, and highlight conserved signaling pathways and regulatory mechanisms in general while illustrating insulin's unique role in specific reproductive processes.     

烷化溶血磷脂ET—18—OCH3对K562细胞作用的研究

为研究烷化溶血磷脂ET－18－OCH3（ALP）的抗白血病效果。本文以K562细胞为研究对象,通过台蓝拒染法测定ALP作用后K562细胞的生长抑制率和生长曲线;甲基纤维素半固体培养法测定克隆原细胞的存尖率;流式细胞仪检测K562细胞P210蛋白表达;TR－PCR半定量法测定细胞的bcr-abl mRNA;采用流式细胞仪进行DNA 及是民镜观察细胞形态学改变。结果显示,K562细胞经ALP处理后细胞生长明显受抑制,呈作用时间和剂量的依赖性,IC50为31.6(24h),22.3(48h),14.8(72h)μg/ml;细胞增殖速度显著降低,克隆原细胞存活曲线呈指数型,而正常对照组细胞的CFU－GM则未受影响;ATP还可使KT562细胞P210及bcr-abl mRNA水平下调,并有诱导细胞凋亡的作用,说明ALP对K562细胞生长具有明显抑制作用,并有诱导细胞凋亡的作用,提示ALP具有一定的抗白血病效应。     

Knockdown of SLC34A2 inhibits cell proliferation,metastasis, and elevates chemosensitivity in glioma

Solute carrier 34 A2 (SLC34A2) is a member of SLC34 family that is a group of phosphate transporters. SLC34A2 has been reported to play critical roles in tumorigenesis and progression. However, the researches about the biological roles of SLC34A2 in glioma have not yet been reported. In this study, we analyzed the expression patterns of SLC34A2 in clinical glioma tumor tissues and cell lines. The results demonstrated that SLC34A2 was generally overexpressed in both glioma tissues and cell lines. To further investigate the roles of SLC34A2 in glioma, lentivirus containing specific SLC34A2 short hairpin RNA (sh-SLC34A2) was used to infect glioma cell lines U251 and U87 for the knockdown of SLC34A2. The following studies proved that SLC34A2 knockdown exhibited suppressive effects on cell proliferation and migration/invasion. SLC34A2 knockdown also inhibited epithelial-mesenchymal transition (EMT) phenotype, as evidenced by the increased E-cadherin expression, and the decreased N-cadherin and fibronectin expressions. Besides, knockdown of SLC34A2 enhanced the temozolomide (TMZ) sensitivity of U251 and U87 cells. In vivo tumorigenicity assay demonstrated that SLC34A2 knockdown inhibited tumor growth. Moreover, SLC34A2 knockdown suppressed the activation of epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in U87 cells. GW2974 (EGFR inhibitor) increased SLC34A2 knockdown-inhibited cell proliferation, migration/invasion, as well as enhanced SLC34A2 knockdown-increased the TMZ sensitivity of glioma cells. These findings suggested that SLC34A2 might be a new potential therapeutic target for the therapy of glioma patients.