Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.

Luteolin, 3′,4′,5,7-tetrahydroxyflavone, is a common flavonoid that exists in many types of plants including fruits, vegetables, and medicinal herbs. Plants rich in luteolin have been used in Chinese traditional medicine for treating various diseases such as hypertension, inflammatory disorders, and cancer. Having multiple biological effects such as anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically. The biological effects of luteolin could be functionally related to each other. For instance, the anti-inflammatory activity may be linked to its anticancer property. Luteolin's anticancer property is associated with the induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis. Furthermore, luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3′-kinase (PI3K)/Akt, nuclear factor kappa B (NF-κB), and X-linked inhibitor of apoptosis protein (XIAP), and stimulating apoptosis pathways including those that induce the tumor suppressor p53. These observations suggest that luteolin could be an anticancer agent for various cancers. Furthermore, recent epidemiological studies have attributed a cancer prevention property to luteolin. In this review, we summarize the progress of recent research on luteolin, with a particular focus on its anticancer role and molecular mechanisms underlying this property of luteolin.

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The PharmMapper online tool is a web server for potential drug target identification by reversed pharmacophore matching the query compound against an in-house pharmacophore model database. The original version of PharmMapper includes more than 7000 target pharmacophores derived from complex crystal structures with corresponding protein target annotations. In this article, we present a new version of the PharmMapper web server, of which the backend pharmacophore database is six times larger than the earlier one, with a total of 23 236 proteins covering 16 159 druggable pharmacophore models and 51 431 ligandable pharmacophore models. The expanded target data cover 450 indications and 4800 molecular functions compared to 110 indications and 349 molecular functions in our last update. In addition, the new web server is united with the statistically meaningful ranking of the identified drug targets, which is achieved through the use of standard scores. It also features an improved user interface. The proposed web server is freely available at http://lilab.ecust.edu.cn/pharmmapper/.

OBJECTIVEThere has been growing evidence that inflammatory markers play a role in the development of type 2 diabetes. We aimed to systematically review prospective studies on the associations of elevated levels of interleukin-6 (IL-6) and C-reactive protein (CRP) with increased risk of type 2 diabetes by conducting a meta-analysis.RESEARCH DESIGN AND METHODSA systematic search of the PubMed, EMBASE, ISI Web of Knowledge, and Cochrane Library databases up until 10 February 2012 was conducted to retrieve prospective studies matched to search terms. We used generalized least-squares trend estimation to assess dose-response relationships. The summary risk estimates were pooled using either fixed-effects or random-effects models to incorporate between-study variation.RESULTSThe meta-analysis, including 10 prospective studies, with a total of 19,709 participants and 4,480 cases, detected a significant dose-response association of IL-6 levels with type 2 diabetes risk (relative risk [RR] 1.31 [95% CI 1.17–1.46]). For CRP, the meta-analysis involving 22 cohorts, with a total of 40,735 participants and 5,753 cases, showed that elevated CRP levels were significantly associated with increased risk of type 2 diabetes (1.26 [1.16–1.37]), with the absence of publication bias. Sensitivity and subgroup analyses further supported the associations.CONCLUSIONSThis meta-analysis provides further evidence that elevated levels of IL-6 and CRP are significantly associated with increased risk of type 2 diabetes.

Upon recognition of bacterial flagellin, the plant receptor FLS2 heterodimerizes with brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) and activates plant defense responses. Because constitutive activation of defense responses is detrimental, plant resistance signaling pathways must be negatively controlled, although the mechanisms involved are unclear. We identified Arabidopsis BIR1 as a BAK1-interacting receptor-like kinase. Knocking out BIR1 leads to extensive cell death, activation of constitutive defense responses, and impairment in the activation of MPK4, a negative regulator of plant resistance (R) protein signaling, by flagellin. sobir1-1, a mutant obtained in a screen for suppressors of the bir1-1 phenotype, rescued cell death observed in bir1-1. SOBIR1 encodes another receptor-like kinase whose overexpression activates cell death and defense responses. Our data suggest that BIR1 negatively regulates multiple plant resistance signaling pathways, one of which is the SOBIR1-dependent pathway identified here.

We found that the high-pressure-synthesized material LiOsO 3 (see Supplementary Information) shows a structural transition at a temperature T s = 140 K. The room-temperature crystal structure of LiOsO 3 was initially examined using powder X-ray diffraction (XRD). The Goldschmidt diagram predicts that LiOsO 3 crystallizes into a LiNbO 3 -type structure 3,10 , and a preliminary refinement of the structure was carried out in the R-3c space group with Os at the 6b site 0,0,0 and O at the 18e siteTo investigate the position of the Li ion we turned to neutron diffraction, which is much more sensitive to Li than XRD. The neutron diffraction patterns collected above T s could be successfully described in the R-3c space group, in agreement with the XRD refinement, with the Li ion at the 6a position 0,0,1/4. Atomic absorption spectrometry (see Supplementary Information) indicated that the average Li mass was 2.77%, which corresponds to the composition Li 0.98 OsO 3 . We have used the stoichiometric composition throughout the structural analysis. The refinement indicated highly anisotropic thermal displacements of the Li ions with considerable extension along the c-axis (Table 1 and Fig. 1), which might indicate that the Li ions are distributed equally among equivalent 12c sites 0,0,z and 0,0,1/2-z either side of the oxygen layer at z = 1/4, as reported for LiNbO 3 and LiTaO 3 (refs 3, 11).The thermal variation of the structure of LiOsO 3 was studied by neutron diffraction for temperatures between 10 and 300 K. Figure 1a-d shows structural data obtained from refinements in the R-3c space group. The lattice parameters ( Fig. 1a) decrease uniformly from 300 K until T s = 140 K, below which the parameter c increases and a decreases with only a small variation in the unit-cell volume. Just below T s , the non-symmetry-breaking strain components e xx + e yy and e zz vary almost linearly (Fig. 1b). These 4 results show that the phase transition is continuous and the strain components behave like a secondary order parameter coupled to a primary one via a linear-quadratic free energy invariant 12 . The primary order parameter must necessarily be symmetry-breaking according to Landau's theory of second-order phase transitions 12 . Furthermore, the anisotropic thermal parameter  33 , which describes Li displacements along the c-axis, increases markedly below T s (Fig. 1c). This indicates that the primary structural instability involves the position of the Li ions along the c-axis (Fig. 1d).Given that the phase transition involves a change in symmetry, we find from representation theory 13 that there are three isotropy subgroups, R-3, R32 and R3c, which maintain the translational invariance of the R-3c space group and allow the transition to be continuous. These space groups were tested by refinement against the neutron diffraction data at 10 K. Note that R-3 and R32 should generate additional reflections below T s which were not observed in the experiment. The refinement in the non-centrosymmetric R3c space group gave the best de...

Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71-7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction.