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Summary: Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of diverse human cancers. We show that the overexpression of PRL-3 protein is not directly associated with its transcript levels, indicating the existence of an underlying posttranscriptional regulation. The 5′ untranslanted region (UTR) of PRL-3 mRNA possesses triple GCCCAG motifs capable of suppressing mRNA translation through interaction with PolyC-RNA-binding protein 1 (PCBP1), which retards PRL-3 mRNA transcript incorporation into polyribosomes. Overexpression of PCBP1 inhibits PRL-3 expression and inactivates AKT, whereas knockdown of PCBP1 causes upregulation of PRL-3 protein levels, activation of AKT, and promotion of tumorigenesis. An inverse correlation between protein levels of PRL-3 and PCBP1 in human primary cancers supports the clinical relevance. [Copyright &y& Elsevier]

About 45% of the world's fruit and vegetables are wasted, resulting in postharvest losses and contributing to economic losses ranging from $10 billion to $100 billion worldwide. Soft rot disease caused by Rhizopus stolonifer leads to postharvest storage losses of sweet potatoes. Nanoscience stands as a new tool in our arsenal against these mounting challenges that will restrict efforts to achieve and maintain global food security. In this study, three nanomaterials (NMs) namely C60, CuO, and TiO2 were evaluated for their potential application in the restriction of Rhizopus soft rot disease in two cultivars of sweet potato (Y25, J26). CuO NM exhibited a better antifungal effect than C60 and TiO2 NMs. The contents of three important hormones, indolepropionic acid (IPA), gibberellic acid 3 (GA-3), and indole-3-acetic acid (IAA) in the infected J26 sweet potato treated with 50 mg/L CuO NM were significantly higher than those of the control by 14.5%, 10.8%, and 24.1%. CuO and C60 NMs promoted antioxidants in both cultivars of sweet potato. Overall, CuO NM at 50 mg/L exhibited the best antifungal properties, followed by TiO2 NM and C60 NM, and these results were further confirmed through scanning electron microscope (SEM) analysis. The use of CuO NMs as an antifungal agent in the prevention of Rhizopus stolonifer infections in sweet potatoes could greatly reduce postharvest storage and delivery losses. [ABSTRACT FROM AUTHOR]

Changes in species composition and diversity are the inevitable consequences of climate change, as well as land use and land cover change. Predicting species richness at regional spatial scales using remotely sensed biophysical variables has emerged as a viable mechanism for monitoring species distribution. In this study, we evaluate the utility of MODIS-based productivity (GPP and EVI) and surface water content (NDSVI and LSWI) in predicting species richness in the semi-arid region of Inner Mongolia, China. We found that these metrics correlated well with plant species richness and could be used in biome- and life form-specific models. The relationships were evaluated on the basis of county-level data recorded from the Flora of Inner Mongolia, stratified by administrative (i.e., counties), biome boundaries (desert, grassland, and forest), and grouped by life forms (trees, grasses, bulbs, annuals and shrubs). The predictor variables included: the annual, mean, maximum, seasonal midpoint (EVImid), standard deviation of MODIS-derived GPP, EVI, LSWI and NDSVI. The regional pattern of species richness correlated with GPPSD (R 2 =0.27), which was also the best predictor for bulbs, perennial herbs and shrubs (R 2 =0.36, 0.29 and 0.40, respectively). The predictive power of models improved when counties with >50% of cropland were excluded from the analysis, where the seasonal dynamics of productivity and species richness deviate patterns in natural systems. When stratified by biome, GPPSD remained the best predictor of species richness in grasslands (R 2 =0.30), whereas the most variability was explained by NDSVImax in forests (R 2 =0.26), and LSWIavg in deserts (R 2 =0.61). The results demonstrated that biophysical estimates of productivity and water content can be used to predict plant species richness at the regional and biome levels. [Copyright &y& Elsevier]

SET is a multi-functional protein in proliferating cells. Some of the proposed functions of SET suggest an important nuclear role. However, the nuclear import pathway of SET is also unknown and the function of SET in neurons is unclear. Presently, using cortical neurons, we report that the nuclear import of SET is mediated by an impα/impβ-dependent pathway. Nuclear localization signal, 168KRSSQTQNKASRKR181, in SET interacts with impα3, which recruits impβ to form a ternary complex, resulting in efficient transportation of SET into nucleus. By in vitro nuclear import assay based on digitonin-permeabilized neurons, we further demonstrated that the nuclear import of SET relies on Ran GTPase. We provide evidence that this nuclear localization of SET is important in neuronal survival. Under basal conditions, SET is predominately nuclear. However, upon death induced by genotoxic stress, endogenous SET decreases in the nucleus and increases in the cytoplasm. Consistent with a toxic role of SET in the cytoplasm, targeted expression of SET to the cytoplasm exacerbates death compared to wild type SET expression which is protective following DNA damage. Taken together, our results indicate that SET is imported into the nucleus through its association with impα3/impβ, and that localization of SET is important in regulation of neuronal death. [ABSTRACT FROM AUTHOR]

Abstract: A spontaneous lymphoma was detected in mice, which was caused by a recessive autosomal mutation. The genetic basis was revealed to be a 5-bp deletion at the splicing donor site of the first intron of the FasL gene, resulting in aberrant transcripts coding for non-functional proteins. This mutation of the FasL gene caused development of lymphoma in all four mouse genetic backgrounds tested and the lymphoma was characterized by an expansion of leucocytes that were TCR+CD3+B220+CD19−CD4−CD8−. Accordingly, severe splenomegaly developed in the mutant mice. Interestingly, thymic hyperplasia was observed in mutant mice at later stages. These results underscore the functional importance of the splicing donor site in the function of the FasL gene and provide an independent evidence for a role of FasL in normal development of lymophocytes. The mutant mice offer another genetically defined mouse model for further studies of the role and mechanism of action of FasL. [Copyright &y& Elsevier]

p53 is a well known tumor suppressor. We show that p53 also regulates osteoblast differentiation, bone formation, and osteoblast-dependent osteoclast differentiation. Indeed, p53-/- mice display a high bone mass phenotype, and p53-/- osteoblasts show accelerated differentiation, secondary to an increase in expression of the osteoblast differentiation factor osterix, as a result. Reporter assays indicate that p53 represses osterix transcription by the minimal promoter in a DNA-binding- independent manner In addition, p53-/- osteoblasts have an enhanced ability to favor osteoclast differentiation, in association with an increase in expression of macrophage-colony stimulating factor, which is under the control of osterix. Furthermore, inactivating p53 is sufficient to rescue the osteoblast differentiation defects observed in mice lacking c-Abl, a p53-interacting protein. Thus, these results identify p53 as a novel regulator of osteoblast differentiation, osteoblast-dependent osteoclastogenesis, and bone remodeling. [ABSTRACT FROM AUTHOR]

Mitochondria play essential roles in cellular energy production via the oxidative phosphorylation system (OXPHOS) consisting of five multiprotein complexes and also in the initiation of apoptosis. NADH:ubiquinone oxidoreductase (complex I) is the largest complex that catalyzes the first step of electron transfer in the OXPHOS system. GRIM-19 was originally identified as a nuclear protein with apoptotic nature in interferon (IFN)- and all-trans-retinoic acid (RA)-induced tumor cells. To reveal its biological role, we generated mice deficient in GRIM-19 by gene targeting. Homologous deletion of GRIM-19 causes embryonic lethality at embryonic day 9.5. GRIM-19-/- blastocysts show retarded growth in vitro and, strikingly, display abnormal mitochondrial structure, morphology, and cellular distribution. We reexamined the cellular localization of GRIM-19 in various cell types and found its primary localization in the mitochondria. Furthermore, GRIM-19 is detected in the native form of mitochondrial complex I. Finally, we show that elimination of GRIM-19 destroys the assembly and electron transfer activity of complex I and also influences the other complexes in the mitochondrial respiratory chain. Our result demonstrates that GRIM-19, a gene product with a specific role in IFN-RA-induced cell death, is a functional component of mitochondrial complex I and is essential for early embryonic development. [ABSTRACT FROM AUTHOR]

Separating geochemical anomalies from background values is crucial for the processing of geochemical data. In the present study, a workflow for identifying geochemical anomalies was constructed by using the direct sampling algorithm of multi-point geostatistics, the maximum entropy model, and local singularity analysis. The smoothing effect and the uncertainty of the unsampled point value in the traditional interpolation method were taken into consideration in this workflow. Based on the statistic of singular exponential distribution of each element with equal probability, the geochemical anomaly probability distribution of each element was obtained (Ag、Cd、Cu、Pb、Zn). Based on the five anomaly probability distributions, the maximum entropy model was used to establish a comprehensive perspective of geochemical anomaly uncertainty evaluation. The validity of the method was verified by analyzing geochemical data of stream sediment samples from the Mila Mountain region in Tibet. The results showed that the prospectivity map of copper deposits generated by the maximum entropy model can effectively link the probability of multivariate geochemical anomalies with the known positions of copper deposits and greatly increase the precision of the potential exploration areas for copper deposits. • Geochemical anomalies identified by direct sampling algorithm and maximum entropy model. • Direct sampling algorithm tackles smoothing effect and uncertainty of missing points. • Maximum entropy model effective in fusing multiple geochemical anomalies information. [ABSTRACT FROM AUTHOR]

• A novel low-cost material 20LH5 was used to clarify the macro–micro relationship. • The mechanical properties (UTS:1090 MPa, YS:533 MPa, TE:47.4%) is remarkable. • There is a nonlinear inverse relationship between the size of dimples and elongation. • The dimple size is linearly proportional to the grain size. • The improvement both in strength and ductility can be achieved by grain refinement. In this study, a novel 20LH5 austenitic stainless steel (AUSS) with various grain sizes was produced. The purpose of this paper is to analyse the effect of the grain size on the tensile fracture morphology and mechanical properties. After a phase reversion process (large ductility cold rolling and annealing), stainless steels with different microstructures comprising coarse grains (CGs) (~9.2 μm) to fine grains (FGs) (~2.1 μm) to ultrafine grains (UFGs) (~1.4 μm) were observed. Tensile tests were then carried out to verify the grain refinement strengthening mechanism. The results show that the mechanical properties in materials that possess UFGs reached a tensile strength of ~1090 MPa, a yield strength of ~530 MPa and an elongation rate of ~47%, which is much better than those of materials with FGs, CGs, and most 300 series AUSSs. Furthermore, the voids in UFG AUSSs were densely distributed and finer than those in the other two counterparts. This indicates that a decreased grain size contributed to a decreased dimple size; that is, the ductility and strength were increased. [ABSTRACT FROM AUTHOR]

Silicoaluminophosphate zeotype with LTA structure (SAPO-LTA) was prepared using ionothermal approach in commercial 1-ethyl-3-methyl imidazolium ([emim]+) ionic liquid. 1H→13C CP/MAS NMR, TGA and CHN elementary analysis results demonstrated that ionic liquid acted as single organic template occluded in pairs in each α cage of the structure. SAPO-LTA exhibited high structural stability after detemplation with excellent BET surface area and microporous volume. Silica content in the products increased with that in the initial reactants with a maximum of SiO 2 wt% lower than 5%. 29Si MAS NMR and NH 3 -TPD results further proved the incorporation of Si in the framework with improved acidity as compared with its aluminophosphate (AlPO) counterpart. SAPO-LTA was active in MTO reaction, showing higher butene and C 5+ product selectivity than that of SAPO-34 with CHA structure, and higher propene to ethylene and lower C 1 to C 4 alkane selectivity in comparison with that of high-silica LTA zeolite (LTA-HSZ). The deactivation of SAPO-LTA catalyst was due to the occlusion of bulky polyaromatic coke in the LTA structure, and could be perfectly recovered during three cycles of regeneration by high-temperature calcination. Image 1 • SAPO-LTA were ionothermally prepared in commercial [emim]+ ionic liquid. • Ionic liquid acted as single organic template occluded in pairs in each α cage of the structure. • The detemplated SAPO-LTA exhibited high structural stability with excellent texture property. • SAPO-LTA with improved acidity was active in MTO reaction showing unique product selectivity. • The deactivated SAPO-LTA could be perfectly recovered by high temperature calcination. [ABSTRACT FROM AUTHOR]

• Plowing decreased species richness and community production and promoted species exchange. • Seeding altered species richness, community production, and functional groups. • Fertilizing altered functional groups and increased community production. • Perennials were more susceptible to plowing and seeding than annuals. The restoration of degraded grasslands can be achieved via multiple methods (e.g., increasing plant propagule input, improving site conditions, and enhancing soil resources); however, little is known about the relative roles of these methods. We conducted an experiment in Inner Mongolia (China) to address how plowing, seeding, and fertilizing influenced species diversity, functional groups, and community productivity in a degraded steppe. Plowing decreased plant species richness by disproportionally enhancing species loss and gain, had no effect on the relative abundance of grasses, legume forbs, and non-legume forbs, and marginally decreased the community biomass. Seeding legumes decreased plant species richness by disproportionally enhancing species loss and gain; seeding legumes or both grasses and legumes significantly affected the relative abundance of grasses, legume forbs, and non-legume forbs. Unexpectedly, seeding decreased aboveground plant community biomass, which might be linked to a nonproportional decrease in per capita biomass. Fertilization did not influence plant species richness, loss, gain, or turnover; however, fertilization increased the relative abundance of grasses and decreased that of legumes and enhanced community biomass. There were significant interactions among plowing, seeding and fertilizing, but these interactions were not synergistic. Over 70% of lost or gained species were perennial plants, implying that perennials might be more susceptible to these treatments than annuals/biennials. These findings suggest that these three restoration practices might have differential effects on plant species diversity, plant functional groups, and plant community productivity in Inner Mongolia and that their combined effects might not be positive for degraded steppes. [ABSTRACT FROM AUTHOR]

Chestnut is a popular food in many countries and is also an important starch source. In previous studies, physicochemical properties of starches have been compared among different Chinese chestnut varieties growing under different conditions. In this study, nine Chinese chestnut varieties from the same farm were investigated for starch physicochemical properties to exclude the effects of growing conditions. The dry kernels had starch contents from 42.7 to 49.3%. Starches from different varieties had similar morphologies and exhibited round, oval, ellipsoidal, and polygonal shapes with a central hilum and smooth surface. Starch had bimodal size distribution and the volume-weighted mean diameter ranged from 7.2 to 8.2 μm among nine varieties. The starches had apparent amylose contents from 23.8 to 27.3% but exhibited the same C-type crystalline structure and similar relative crystallinity, ordered degree, and lamellar structure. The gelatinization onset, peak, and conclusion temperatures ranged from 60.4 to 63.9 °C, from 64.8 to 68.3 °C, and from 70.5 to 74.5 °C, respectively, among nine starches; and the peak, hot, breakdown, final, and setback viscosities ranged from 5524 to 6505 mPa s, from 3042 to 3616 mPa s, from 2205 to 2954 mPa s, from 4378 to 4942 mPa s, and from 1326 to 1788 mPa s, respectively. The rapidly digestible starch, slowly digestible starch, and resistant starch ranged from 2.6 to 3.7%, from 5.7 to 12.7%, and from 84.4 to 90.7%, respectively, for native starch, and from 79.6 to 89.5%, from 1.3 to 3.8%, and from 7.1 to 17.4%, respectively, for gelatinized starch. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24-72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3β), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Background: Phosphatase of regenerating liver-3 (PRL-3), a protein tyrosine phosphatase, is highly expressed in multiple human cancers and strongly implicated in tumor progression and cancer metastasis. However, the mechanisms by which PRL-3 promotes cancer cell migration, invasion, and metastasis are not very well understood. In this study, we investigated the contribution and molecular mechanisms of PRL-3 in ovarian cancer progression.Methods: PRL-3 protein expression was detected on ovarian cancer tissue microarrays using immunohistochemistry. Stable PRL-3 depleted cell lines were generated using short hairpin RNA (shRNA) constructs. The migration and invasion potential of these cells were analyzed using Transwell and Matrigel assays, respectively. Immunoblotting and immunofluorescence were used to detect protein levels and distribution in PRL-3-ablated cells and the control cells. Cell morphology was observed with hematoxylin-eosin staining and transmission electron microscopy. Finally, PRL-3-ablated and control cells were injected into nude mice for xenograft tumorigenicity assays.Results: Elevated PRL-3 expression was detected in 19% (26 out of 135) of human ovarian cancer patient samples, but not in normal ovary tissues (0 out of 14). Stable depletion of PRL-3 in A2780 ovarian cancer cells resulted in decreased migration ability and invasion activity compared with control parental A2780 cells. In addition, PRL-3-ablated cells also exhibited flattened morphology and extended lamellipodia. To address the possible molecular basis for the altered phenotypes associated with PRL-3 down-regulation, we assessed the expression profiles of various proteins involved in cell-matrix adhesion. Depletion of PRL-3 dramatically enhanced both RNA and protein levels of the cell surface receptor integrin α2, but not its heterologous binding partner integrin β1. Inhibition of PRL-3 also correlated with elevated expression and phosphorylation of paxillin. A pronounced increase in the expression and activation of c-fos, a transcriptional activator of integrin α2, was observed in these PRL-3 knock-down cells. Moreover, forced expression of EGFP-PRL-3 resulted in the suppression of both integrin α2 and c-fos expression in A2780 cells. Significantly, using a xenograft tumor model, we observed a greatly reduced tumorigenicity of A2780 PRL-3 knock-down cells in vivo.Conclusions: These results suggest that PRL-3 plays a critical role in ovarian cancer tumorigenicity and maintaining the malignant phenotype. PRL-3 may inhibit c-fos transcriptional regulation of integrin α2 signaling. Our results strongly support a role for PRL-3 as a promising therapeutic target and potential early biomarker in ovarian cancer progression. [ABSTRACT FROM AUTHOR]