Multidrug-resistant cancer cells and cancer stem cells hijack cellular systems to circumvent systemic therapies,can natural products reverse this?

Chemotherapy is one of the most effective and broadly used approaches for cancer management and many modern regimes can eliminate the bulk of the cancer cells. However, recurrence and metastasis still remain a major obstacle leading to the failure of systemic cancer treatments. Therefore, to improve the long-term eradication of cancer, the cellular and molecular pathways that provide targets which play crucial roles in drug resistance should be identified and characterised. Multidrug resistance (MDR) and the existence of tumor-initiating cells, also referred to as cancer stem cells (CSCs), are two major contributors to the failure of chemotherapy. MDR describes cancer cells that become resistant to structurally and functionally unrelated anti-cancer agents. CSCs are a small population of cells within cancer cells with the capacity of self-renewal, tumor metastasis, and cell differentiation. CSCs are also believed to be associated with chemoresistance. Thus, MDR and CSCs are the greatest challenges for cancer chemotherapy. A significant effort has been made to identify agents that specifically target MDR cells and CSCs. Consequently, some agents derived from nature have been developed with a view that they may overcome MDR and/or target CSCs. In this review, natural products-targeting MDR cancer cells and CSCs are summarized and clustered by their targets in different signaling pathways.     

The past vs. the tiny: historical science and the abductive arguments for realism

Scientific realism is fundamentally a view about unobservable things, events, processes, and so on, but things can be unobservable either because they are tiny or because they are past. The familiar abductive arguments for scientific realism lend more justification to scientific realism about the tiny than to realism about the past. This paper examines both the “basic” abductive arguments for realism advanced by philosophers such as Ian Hacking and Michael Devitt, as well as Richard Boyd’s version of the inference to the best explanation of the success of science, and shows that these arguments provide less support to historical than to experimental realism. This is because unobservably tiny things can function both as unifiers of the phenomena and as tools for the production of new phenomena, whereas things in the past can only serve as unifiers of the phenomena. The upshot is that realists must not suppose that by presenting arguments for experimental realism they have thereby defended realism in general.     

Fishes of Bly Tunnel, Lassen County, California

Leon Bly Tunnel, which connects Eagle Lake to Willow Creek, was investigated to see if the water issuing from the tunnel was lake water or spring water and to check reports of its being inhabited by fish. We found that the water was similar to that of highly alkaline Eagle Lake, despite a block placed in the tunnel in 1986. Five species of fish were found in the tunnel, the same species inhabiting both Willow Creek and Eagle Lake, although the creek was much warmer and less alkaline than the lake. The fish originated from the creek. Fish in the tunnel were either not feeding or were consuming snails ( Vorticifex sp.), the principal invertebrate present. The largest fish (35 cm SL) captured were rainbow trout ( Oncorhynchus mykiss ).     

Where explanation ends: Understanding as the place the spade turns in the social sciences

Explanations implicitly end with something that makes sense, and begin with something that does not make sense. A statistical relationship, for example, a numerical fact, does not make sense; an explanation of this relationship adds something, such as causal information, which does make sense, and provides an endpoint for the sense-making process. Does social science differ from natural science in this respect? One difference is that in the natural sciences, models are what need “understanding.” In the social sciences, matters are more complex. There are models, such as causal models, which need to be understood, but also depend on background knowledge that goes beyond the model and the correlations that make it up, which produces a regress. The background knowledge is knowledge of in-filling mechanisms, which are normally made up of elements that involve the direct understanding of the acting and believing subjects themselves. These models, and social science explanations generally, are satisfactory only when they end the regress in this kind of understanding or use direct understanding evidence to decide between alternative mechanism explanations.     

Not just angiotensinases: new roles for the angiotensin-converting enzymes

The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Angiotensin II, the primary bioactive peptide of the RAS, is generated from angiotensin I by angiotensin-converting enzyme (ACE). A homologue of ACE, ACE2, is able to convert angiotensin II to a peptide with opposing effects, angiotensin-(1-7). It is proposed that disturbance of the balance of ACE and ACE2 expression and/or function is important in pathologies in which angiotensin II plays a role. These include cardiovascular and renal disease, lung injury and liver fibrosis. The critical roles of ACE and ACE2 in regulating angiotensin II levels have traditionally focussed attention on their activities as angiotensinases. Recent discoveries, however, have illuminated the roles of these enzymes and of the ACE2 homologue, collectrin, in intracellular trafficking and signalling. This paper reviews the key literature regarding both the catalytic and non-catalytic roles of the angiotensin-converting enzyme gene family.     

计算机进行生物数据深层分析方法导论

本书既注重理论性，又具有实用性。作者深入浅出地介绍了生物学研究中最常见的并且是新的计算机深入分析的方法，这些现代计算方法使数据分析不再依赖于先验假设。作者在本书中有针对性地设计了一些练习，并给出了参考答案，读者可通过做习题、对答案，检查自己对书中内容的理解。作者在该书中给出的例子都来源于实际的生物学研究，     

Newly identified genetic risk variants for celiac disease related to the immune response

Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.