XPO1 inhibition with selinexor synergizes with proteasome inhibition in neuroblastoma by targeting nuclear export of IkB

Across many cancer types in adults, upregulation of the nuclear-to-cytoplasmic transport protein Exportin-1 (XPO1) correlates with poor outcome and responsiveness to selinexor, an FDA-approved XPO1 inhibitor. Similar data are emerging in childhood cancers, for which selinexor is being evaluated in early phase clinical studies. Using proteomic profiling of primary tumor material from patients with high-risk neuroblastoma, as well as gene expression profiling from independent cohorts, we have demonstrated that XPO1 overexpression correlates with poor patient prognosis. Neuroblastoma cell lines are also sensitive to selinexor in the low nanomolar range. Based on these findings and knowledge that bortezomib, a proteasome inhibitor, blocks degradation of XPO1 cargo proteins, we hypothesized that combination treatment with selinexor and bortezomib would synergistically inhibit neuroblastoma cellular proliferation. We observed that selinexor promoted nuclear retention of IkB and that bortezomib augmented the ability of selinexor to induce cell-cycle arrest and cell death by apoptosis. This synergy was abrogated through siRNA knockdown of IkB. The synergistic effect of combining selinexor and bortezomib in vitro provides rationale for further investigation of this combination treatment for patients with high-risk neuroblastoma.     

Appearance of the T-cell marker CD8 on B chronic lymphatic leukemia cells in long-term cultures

Summary Long-term cultures of highly purified B chronic lymphatic leukemia cells (B-CLL), were established. The B-CLL lymphocytes acquired the CD8 T cell marker in long-term cultures while still retaining their surface immunoglobulins. In confirmation of previous results, the cultured B-CLL lymphocytes released factor(s) into the culture medium that suppressed the allogeneic mixed-lymphocyte reaction. No correlation was found between the appearance of the CD8 T cell surface marker and onset of suppressor activity.     

Assessment of species limits in African ‘brown buntings’ (Emberiza,Passeriformes) based on mitochondrial and nuclear sequence data

We estimated a phylogeny for 10 taxa currently placed in four polytypic species that collectively encompass the African ‘brown buntings’: Cape Bunting Emberiza capensis, Cinnamon‐breasted Bunting Emberiza tahapisi, Lark‐like Bunting Emberiza impetuani and House Bunting Emberiza striolata. We made use of the mitochondrial cytochrome b gene and the nuclear introns 6–7 of ornithine decarboxylase (ODC), and intron 2 of myoglobin. There was substantial cytochrome b sequence divergence between taxa currently treated as conspecific: sahari vs. striolata (2.6–3.1% (uncorrected‐p); 3.0–3.6% (HKY + I)), and goslingi vs. tahapisi (4.4–4.7% (uncorrected‐p); 5.4–5.9% (HKY + I)). The degree of divergence of the nuclear loci among taxa was limited, and these loci lacked reciprocal monophyly, most likely as a consequence of incomplete lineage sorting. A single representative of the taxon septemstriata, generally treated as a member of the dark‐throated tahapisi group, here appears to be genetically consistent with the grey‐throated goslingi, and may be of hybrid origin. All other taxa allocated to E. striolata and E. tahapisi make up four reciprocally monophyletic groups consistent with sahari, striolata, tahapisi and goslingi, respectively. The extent of genetic evidence suggests that these taxa have been evolving as separate evolutionary lineages for a long time. This is further manifested in several morphological and vocal characteristics described previously, and we propose that these divergent taxa be treated as separate species: Cinnamon‐breasted Bunting Emberiza tahapisi, Gosling's Bunting Emberiza goslingi, Striolated Bunting Emberiza striolata and House Bunting Emberiza sahari. We do not propose any taxonomic changes regarding Emberiza impetuani or Emberiza capensis.     

Apoptotic cells represent a dynamic stem cell niche governing proliferation and tissue regeneration

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多甲藻对不同光照强度的反应:色素沉着及暗光适应的可能性

在ＨＰＬＣ色素分析的基础上，研究了多甲藻对不同光照强度（１６．６～２５０μ．Ｅｍ＾０２ｓ＾－１）的反应。类胡萝卡素中最重要的多甲藻素和硅甲藻黄素占叶黄素总量的９０％，随着光照强度的逐步增加，多甲藻细胞中叶绿素ａ含量呈现明显的下降趋势。结果表明硅甲藻黄素和β胡萝卜素具有光作用：１）当多甲藻暴露于较强光下时，硅甲藻黄素／叶绿素ａ之比呈现出明显增加的趋势，β胡萝卜素／叶绿素ａ之比也显现出明显的增加趋势；     

CircRNAs: role in human diseases and potential use as biomarkers

Circular RNAs (circRNAs) are a class of endogenous RNAs characterized by a covalent loop structure. In comparison to other types of RNAs, the abundance of circRNAs is relatively low but due to the circular configuration, their stability is very high. In addition, circRNAs display high degree of tissue specificity. The sponging activity of circRNAs toward microRNAs is the best-described mode of action of circRNAs. However, the ability of circRNAs to bind with specific proteins, as well as to encode short proteins, propose alternative functions. This review introduces the biogenesis of circRNAs and summarizes the roles played by circRNAs in human diseases. These include examples of their functional roles in several organ-specific cancers, such as head and neck and breast and lung cancers. In addition, we review potential functions of circRNAs in diabetes, cardiovascular, and neurodegenerative diseases. Recently, a growing number of studies have demonstrated involvement of circRNAs in a wide spectrum of signaling molecular pathways, but at the same time many different and controversial views on circRNAs role and function are emerging. We conclude by offering cellular homeostasis generated by networks comprising circular RNAs, other non-coding RNAs and RNA-binding proteins. Accordingly, it is predictable that circRNAs, due to their highly stable nature and remarkable tissue specificity, will emerge as reliable biomarkers of disease course and treatment efficacy.Subject terms: Cancer, Cell biology, Molecular biology     

Some aspects of the ecology of the desert snail Sphincterochila prophetarum in relation to energy and water flow

Summary Between 1976–1978, we studied the ecology of the Sphincterochila prophetarum, the most common snail, on stony slopes in Northern Negev. Energy and water flow determinations were made at the individual and population levels on a field observation basis and metabolic data were derived from laboratory simulations.The snails are active during 5–7% of the time during the year, while the remaining 95% of the time, the snails are in aestivation under stones. The energy and water inputs during the short feeding periods are very fast. Only 8% of the total energy in the eaten food are assimilated. Eighty-nine percent of the total assimilated energy are utilized in respiration during the various periods of activity and dormancy.The water loss during the feeding and activity period is about 37% of the total annual input. The snails lose twice as much the amount of water during the winter dormancy periods than in the summer dormancy period.Dedicated to Prof. Evenari and Dr. Springer