Myriad field, laboratory, and modeling studies show that nutrient availability plays a fundamental role in regulating CO2 exchange between the Earth's biosphere and atmosphere, and in determining how ...carbon pools and fluxes respond to climatic change. Accordingly, global models that incorporate coupled climate–carbon cycle feedbacks made a significant advance with the introduction of a prognostic nitrogen cycle. Here we propose that incorporating phosphorus cycling represents an important next step in coupled climate–carbon cycling model development, particularly for lowland tropical forests where phosphorus availability is often presumed to limit primary production. We highlight challenges to including phosphorus in modeling efforts and provide suggestions for how to move forward.
Speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) is a cullin 3-based E3 ubiquitin ligase adaptor protein that plays a crucial role in ubiquitin-mediated protein degradation. ...Recently, SPOP has attracted major research attention as it is frequently mutated in a range of cancers, highlighting pleiotropic tumorigenic effects and associations with treatment resistance. Structurally, SPOP contains a functionally critical N-terminal meprin and TRAF homology (MATH) domain for many SPOP substrates. SPOP has two other domains, including the internal Bric-a-brac-Tramtrack/Broad (BTB) domain, which is linked with SPOP dimerization and binding to cullin3, and a C-terminal nuclear localization sequence (NLS). The dysregulation of SPOP-mediated proteolysis is associated with the development and progression of different cancers since abnormalities in SPOP function dysregulate cellular signaling pathways by targeting oncoproteins or tumor suppressors in a tumor-specific manner. SPOP is also involved in genome stability through its role in the DNA damage response and DNA replication. More recently, studies have shown that the expression of SPOP can be modulated in various ways. In this review, we summarize the current understanding of SPOP’s functions in cancer and discuss how to design a rational therapeutic target.
A novel single-cell analysis platform was fabricated using solid-state zinc-coadsorbed carbon quantum dot (ZnCQDs) nanocomposites as an electrochemiluminescence (ECL) probe for the detection of ...breast cancer cells and evaluation of the CD44 expression level. Solid-state ZnCQDs nanocomposite probes were constructed through the attachment of ZnCQDs to gold nanoparticles and then the loading of magnetic beads to amplify the ECL signal, exhibiting a remarkable 120-fold enhancement of the ECL intensity. Hyaluronic acid (HA)-functionalized solid-state probes were used to label a single breast cancer cell by the specific recognition of HA with CD44 on the cell surface, revealing more stable, sensitive, and effective tagging in comparison with the water-soluble CQDs. This strategy exhibited a good analytical performance for the analysis of MDA-MB-231 and MCF-7 single cells with linear range from 1 to 18 and from 1 to 12 cells, respectively. Furthermore, this single-cell analysis platform was used for evaluation of the CD44 expression level of these two cell lines, in which the MDA-MB-231 cells revealed a 2.8–5.2-fold higher CD44 expression level. A total of 20 single cells were analyzed individually, and the distributions of the ECL intensity revealed larger variations, indicating the high cellular heterogeneity of the CD44 expression level on the same cell line. The as-proposed single-cell analysis platform might provide a novel protocol to effectively study the individual cellular function and cellular heterogeneity.
The Rock Quality Designation (RQD) index is defined as the percentage of the borehole core or scanline that consists of intact lengths ≥0.1 m, and has been widely used as an engineering measure of ...the jointing degree of a rock mass. The directivity of RQD, which means the value of the RQD obtained from drilling cores or scanlines with different orientations can be different for a given site, is usually regarded as a drawback by researchers and engineers. This study presents a new perspective for the directivity of RQD: the directivity of RQD should be regarded as an advantage of the index because it essentially reflects the anisotropy of rock masses. Because a smaller value of the RQD index implies a better reproduction of the different jointing degrees of different rock masses, its minimum value is selected as the representative RQD (RQDr), and its corresponding direction is called as the representative direction of RQD. In this study, to obtain the RQDr and its representative direction, theoretical formulas are derived to calculate the RQD in any direction based on some known RQDs in different directions. The proposed formulas consider the variance of the discontinuity orientations and sizes for a discontinuity set, use the traditional concept of RQD, and possess the associated simplicity; they only require sampling a few additional discontinuity orientations. Therefore, the proposed approach is easy to understand and apply in engineering practices. An anisotropy index of jointing degree (AIjd) is defined to quantitatively describe the anisotropy of jointing degree for rock masses. The range of AIjd is from 0 to 100, and the larger value of AIjd reflects stronger anisotropy of jointing degree of a rock mass. In this study, a hypothetical three-dimensional discontinuity network is constructed by performing Monte Carlo simulations, based on which the generated data are analyzed to validate the proposed method. The comparison between the calculated and actual values of the RQD shows that (a) the difference between the calculated and actual values of the RQD is <4 for >86.0% of the 1368 scanlines examined with respect to 12 scanline groups, except SG4–1 group, for which the proportion is 66.2%; (b) the difference between the calculated and actual values of the RQD is <6 for >96.2% of the 1368 scanlines examined with respect to 12 scanline groups, except SG4–1, for which the proportion is 86.7%; and (c) the proposed method of calculating the RQD in any direction based on some known RQDs in different directions is satisfactory. In addition, the comparisons show that the calculated RQDr and representative direction exhibit a good agreement with the actual results, and hence, the proposed method for this purpose is satisfactory. Moreover, an actual rock mass of a slope around the Qingshan Lake National Forest Park in China is investigated, and the results show that the proposed method is valid for that rock mass.
•The directivity of RQD is an advantage because it reflects the anisotropy of rock masses.•Theoretical formulas are derived to calculate the RQD in any direction.•The proposed formulas consider the variance of the discontinuity orientations and sizes.•The representative RQD and representative direction of RQD are defined.•An anisotropy index of jointing degree for rock masses is defined.
This study was to estimate the prevalence and characteristics of
from 1,850 retail meat and meat products in China during July 2011 to June 2016. The samples were collected covering most provincial ...capitals in China, including 604 raw meat, 601 quick-frozen meat, and 645 ready-to-eat meat. Using the qualitative and quantitative methods, all 39 cities had
-positive samples, and
was detected in 35.0% (647/1,850) of the samples. The levels of
in retail meat showed that the MPN value of the majority of the positive samples ranged from 0.3 to 100 MPN/g. Twenty-four antibiotics were used to test all 868
isolates for antibiotic susceptibility. Only 11 isolates (1.26%) were susceptible to all antibiotics, whereas most isolates (821/868, 94.6%) showed resistance or intermediary resistance to more than three or more antibiotics. Of these strains, 104 (12.0%) were resistant to more than 10 antibiotics. However, the most frequent resistance was observed to ampicillin (85.4%), followed by penicillin (84.6%), erythromycin (52.7%), tetracycline (49.3%), kanamycin (45.3%), telithromycin (30.1%), clindamycin (29.6%), streptomycin (21.1%), norfloxacin (20.4%), gentamicin (19.4%), fusidic acid (18.4%), ciprofloxacin (16.9%), chloramphenicol (13.1%), amoxycillin/clavulanic acid (11.0%), and others (<10%). 7.4% of isolates (62/868) were confirmed as methicillin-resistance
(MRSA). By molecular typing analysis, there were 164
types and 111 STs were identified, including 15 novel
types and 65 newly STs by multilocus sequence typing (MLST) and
typing. Despite the wide genetic diversity observed among the 868 isolates, a great proportion of the population belonged to finite number of major clones: ST1-t127 (93/868, 10.7%) and ST7-t091 (92/868, 10.6%), ST5-t002 (42/868, 4.8%), ST398-t034 (40/868, 4.6%), ST188-t034 (38/868, 4.4%), ST59-t437 (30/868, 3.5%), ST6-t701 (29/868, 3.3%), and ST9-t899 (27/868, 3.1%) in China. This study reflects
was readily detected in Chinese retail meat and meat products but the level were not very excessive. In this study, the high antibiotic resistance is alarming and raising public health concern. In additions, most of molecular types of isolates have been linked to human infections around the world, indicating that these types of
in China have a theoretical pathogenic potential.
Synapse structures, including neuronal and immunological synapses, can be seen as the plasma membrane contact sites between two individual cells where information is transmitted from one cell to the ...other. The distance between the two plasma membranes is only a few tens of nanometers, but these areas are densely populated with functionally different proteins, including adhesion proteins, receptors, and transporters. The narrow space between the two plasma membranes has been a barrier for resolving the synaptic architecture due to the diffraction limit in conventional microscopy (~250 nm). Various advanced super-resolution microscopy techniques, such as stimulated emission depletion (STED), structured illumination microscopy (SIM), and single-molecule localization microscopy (SMLM), bypass the diffraction limit and provide a sub-diffraction-limit resolving power, ranging from 10 to 100 nm. The studies using super-resolution microscopy have revealed unprecedented details of the nanoscopic organization and dynamics of synaptic molecules. In general, most synaptic proteins appear to be heterogeneously distributed and form nanodomains at the membranes. These nanodomains are dynamic functional units, playing important roles in mediating signal transmission through synapses. Herein, we discuss our current knowledge on the super-resolution nanoscopic architecture of synapses and their functional implications, with a particular focus on the neuronal synapses and immune synapses.
Salmonella enterica subsp. enterica serovar 1,4,5,12:i:- is a monophasic variant of Salmonella Typhimurium, which has recently been recognized as an emerging cause of infection worldwide. This ...bacterium has also ranked among the four most frequent serovars causing human salmonellosis in China. However, there are no reports on its contamination in Chinese food. Serotyping, polymerase chain reaction, antibiotic resistance, virulotyping, and multilocus sequence typing (MLST) assays were used to investigate the prevalence of this serological variant in food products in China, and to determine phenotypic and genotypic difference of monophasic isolates and Salmonella Typhimurium isolated over the same period. Salmonella 1,4,5,12:i:- was prevalent in various food sources, including beef, pork, chicken, and pigeon. The study also confirmed the high prevalence (53.8%) of resistance to ampicillin, streptomycin, sulfonamides, and tetracycline in Salmonella 1,4,5,12:i:-, which was higher than that in Salmonella Typhimurium. Moreover, Salmonella 1,4,5,12:i:- isolates in our study were different from Salmonella Typhimurium isolates by the absence of three plasmid-borne genes (spvC, pefA, and rck) and the presence of gipA in all isolates. All Salmonella 1,4,5,12:i:- isolates demonstrated MLST pattern ST34. Genomic deletions within the fljBA operon and surrounding genes were only found in Salmonella 1,4,5,12:i:- isolates, with all isolates containing a deletion of fljB. However, hin and iroB were identified in all Salmonella 1,4,5,12:i:- isolates. Three different deletion profiles were observed and two of them were different from the reported Salmonella 1,4,5,12:i:- clones from Spain, America, and Italy, which provided some new evidence on the independent evolution of the multiple successful monophasic clones from Salmonella Typhimurium ancestors. This study is the first report of Salmonella 1,4,5,12:i:- in food products from China. The data are more comprehensive and representative, providing valuable information for epidemiological studies, risk management, and public health strategies.
Novel 1,4-naphthoquinones possessing indole scaffolds were prepared by the reaction of 2-hydroxy-1,4-naphthoquinone-substituted salicylic aldehydes and indoles using In(OTf)₃ as a catalyst. The ...method has the advantages of simple operation, mild reaction conditions, and friendly environment.
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•The development of novel LSD1-based dual-target agents were summarized.•The rational design and SARs of novel LSD1-based dual-target agents were presented in details.•Benefits of ...LSD1-based dual-target agents were summarized, while limitations were raised.
Lysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1 inhibitors synergistically improve the efficacy of additional antitumor drugs, which encourages numerous medicinal chemists to innovate and develop new-generation LSD1-based dual-target agents. This review discusses the theoretical foundation of the design of LSD1-based dual-target agents and summarizes their possible applications in treating cancers.
Super‐resolution imaging has revealed that key synaptic proteins are dynamically organized within sub‐synaptic domains (SSDs). To examine how different inhibitory receptors are regulated, we carried ...out dual‐color direct stochastic optical reconstruction microscopy (dSTORM) of GlyRs and GABAARs at mixed inhibitory synapses in spinal cord neurons. We show that endogenous GlyRs and GABAARs as well as their common scaffold protein gephyrin form SSDs that align with pre‐synaptic RIM1/2, thus creating trans‐synaptic nanocolumns. Strikingly, GlyRs and GABAARs occupy different sub‐synaptic spaces, exhibiting only a partial overlap at mixed inhibitory synapses. When network activity is increased by 4‐aminopyridine treatment, the GABAAR copy numbers and the number of GABAAR SSDs are reduced, while GlyRs remain largely unchanged. This differential regulation is likely the result of changes in gephyrin phosphorylation that preferentially occurs outside of SSDs. The activity‐dependent regulation of GABAARs versus GlyRs suggests that different signaling pathways control the receptors' sub‐synaptic clustering. Taken together, our data reinforce the notion that the precise sub‐synaptic organization of GlyRs, GABAARs, and gephyrin has functional consequences for the plasticity of mixed inhibitory synapses.
SYNOPSIS
This study analyzes the internal organization of mixed inhibitory spinal cord synapses using dSTORM and reveals the existence of trans‐synaptic nanocolumns containing GlyRs and GABAARs that are differentially regulated in response to altered network activity.
Sub‐synaptic domains (SSDs) are aligned in trans‐synaptic nanocolumns at inhibitory synapses.
SSDs formed by GlyRs and GABAARs are differentially spatially organized at mixed inhibitory synapses.
GABAARs but not GlyRs show activity‐dependent regulation at mixed inhibitory synapses.
Gephyrin phosphorylation is compartmentalized in SSDs within the synaptic scaffold.
This study analyzes the internal organization of mixed inhibitory spinal cord synapses using dSTORM and reveals the existence of trans‐synaptic nanocolumns containing GlyRs and GABAARs that are differentially regulated in response to altered network activity.
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