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Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.

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To explore a new underlying molecular mechanism of Huangkui Extract Powder (HKEP) in the alleviation of diabetic nephropathy (DN). Murine immortalized podocytes were divided into (i) normal glucose (NG, 5.6 mM), (ii) NG + HKEP (0.45 g/L), (iii) HG, and (iv) HG + HKEP (0.45 g/L) groups. MTT assay and flow cytometry were used to detect the podocyte proliferation, apoptosis and cell cycle. Cell viability was inhibited, and apoptosis increased in(iii) HG group compared with (i) NG group (p<0.05). mRNA and protein expression of nephrin and podocin significantly decreased in (iii) HG group compared with (i) NG group (p<0.05). When compared with (iii) HG group, (iv) HG + HKEP group had higher cell viability, lower apoptotic rate and higher mRNA and protein expression of nephrin and podocin (p<0.05). HKEP can attenuate HG-induced podocyte damage, which may be one of the mechanisms of HKEP for attenuating DN.

Explorar un nuevo mecanismo molecular subyacente del extracto del polvo de Huangkui (HKEP) en el alivio de la nefropatía diabética (ND). Los podocitos murinos inmortalizados se dividieron en (i) grupos de glucosa normal (NG, 5,6 mM), (ii) NG + HKEP (0,45 g/L), (iii) HG y (iv) HG + HKEP (0,45 g/L). Se utilizaron el ensayo MTT y la citometría de flujo para detectar la proliferación de podocitos, la apoptosis y el ciclo celular. La viabilidad celular se inhibió y la apoptosis aumentó en el grupo (iii) HG en comparación con el grupo (i) NG (p<0,05). La expresión de ARNm y proteínas de nefrina y podocina disminuyó significativamente en el grupo (iii) HG en comparación con el grupo (i) NG (p<0,05). En comparación con el grupo (iii) HG, el grupo (iv) HG + HKEP tuvo una mayor viabilidad celular, una tasa de apoptosis más baja y una expresión de ARNm y proteínas más altas de nefrina y podocina (p<0,05). HKEP puede atenuar el daño de los podocitos inducido por HG, que puede ser uno de los mecanismos de HKEP para atenuar la DN.

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ABSTRACT One-year-old Glycyrrhiza uralensis Fisch. ex DC, Fabaceae, was treated with three exogenous phytohormones in June and July, namely gibberellin, auxin (indole-3-acetic acid), methyl jasmonate at different concentrations. Control plants were treated with water. Roots of controls and hormones-treated G. uralensis plants were harvested at different times, and the contents of seven main chemical components were determined. Root glycyrrhizic acid content of plants treated in June increased significantly compared with controls, and the difference was significant. As for plants treated in July, root glycyrrhizic acid content increased in which sprayed with appropriate concentrations of hormones, but the effects of hormones were more evident in plants treated in June coincided with the vigorous growth period than those treated in July. Gibberellin at 40 mg/l and auxin at 40 mg/l applied in the two treatment periods significantly promoted the accumulation of glycyrrhizic acid in G. uralensis root. Treatment with methyl jasmonate at 100 and 25 mg/l in June and July, respectively, also increased glycyrrhizic acid content significantly. The determination of major active compositions indicated that liquiritin, isoliquiritin, isoliquiritin apioside and liquiritin apioside contents were positively related to glycyrrhizic acid content. The study preliminarily found phytohormones and the main chemical components associated with glycyrrhizic acid content, and these discoveries could provide a basis for establishing a chemical control network with glycyrrhizic acid as the core, confirming the secondary product metabolic pathways in the network and completely uncovering synthesis mechanism underlying glycyrrhizic acid-combined functional gene polymorphism.

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OBJECTIVE: To determine whether general cognitive ability, basic mathematic processing, and mathematic attainment are universally affected by gestation at birth, as well as whether mathematic attainment is more strongly associated with cohort-specific factors such as schooling than basic cognitive and mathematical abilities. STUDY DESIGN: The Bavarian Longitudinal Study (BLS, 1289 children, 27-41 weeks gestational age [GA]) was used to estimate effects of GA on IQ, basic mathematic processing, and mathematic attainment. These estimations were used to predict IQ, mathematic processing, and mathematic attainment in the EPICure Study (171 children <26 weeks GA). RESULTS: For children born <34 weeks GA, each lower week decreased IQ and mathematic attainment scores by 2.34 (95% CI: -2.99, -1.70) and 2.76 (95% CI: -3.40, -2.11) points, respectively. There were no differences among children born 34-41 weeks GA. Similarly, for children born <36 weeks GA, mathematic processing scores decreased by 1.77 (95% CI: -2.20, -1.34) points with each lower GA week. The prediction function generated using BLS data accurately predicted the effect of GA on IQ and mathematic processing among EPICure children. However, these children had better attainment than predicted by BLS. CONCLUSIONS: Prematurity has adverse effects on basic mathematic processing following birth at all gestations <36 weeks and on IQ and mathematic attainment <34 weeks GA. The ability to predict IQ and mathematic processing scores from one cohort to another among children cared for in different eras and countries suggests that universal neurodevelopmental factors may explain the effects of gestation at birth. In contrast, mathematic attainment may be improved by schooling.

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OBJECTIVE: To investigate the factors predicting spontaneous clearance of hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort from childhood into adult life. STUDY DESIGN: Children with chronic hepatitis B virus (HBV) infection without treatment were followed longitudinally every 6 months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B vaccination history and the maternal HBV markers also were studied. RESULTS: A total of 349 children (205 male) were followed for 20.6 ± 4.4 years with initial ages of 8.4 ± 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The HBsAg titers decayed with age, with an average annual clearance rate of 0.58%. Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers (P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for spontaneous HBsAg clearance (P = .04). Those with HBsAg titer ≤1000 IU/mL at enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio = 5.23; P < .001). Using HBsAg titer ≤1000 IU/mL to predict HBsAg clearance, the sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%, and negative predictive value is 91.4%. CONCLUSIONS: During long-term follow-up, spontaneous HBsAg clearance is most likely to occur in a patient born to a non-HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an initial HBsAg level ≤1000 IU/mL.

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In Taiwan, oral cancer is the fourth leading cause of male cancer mortality, and is still increasing. The Basiodiomycete, Agaricus brasiliensis Murill (ABM) is a dietary mushroom and has been known for its immuneenhancing, antitumor, antioxidation, antiviral and antimutagenesis functions. However, the exact anticancer mechanisms of ABM on human oral cancer cells are still unclear. In the present study, we investigated the effects of 50% ethanol crude extracts and hot water extracts of ABM on oral cancer CAL 27 cells. We observed that 0.9 mg/ml and 0.7 mg/ml of ABM 50% ethanol crude extracts and hot water, respectively, caused morphological changes and significantly reduced cell viability after 48-h treatment. The results showed that both extracts of ABM inhibited cell proliferation, increased the Ca(2+) release, reduced the mitochondria membrane potential (ΔΨm), and caused cell cycle arrest in the G(0)/G(1) phase, which contributed to apoptosis. Additionally, ABM induced DNA fragmentation, a characteristic of apoptosis and the expressions of apoptosis-related proteins, including apoptosis-inducing factor, cytochrome c, and caspase-3, were increased. Overall, we demonstrated that 50% ethanol crude extract and hot water extracts of ABM were able to induce apoptotic cell death in CAL 27 cells via the release of cytochrome c from mitochondria into the cytoplasm and activation of caspase-3 in vitro.

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Propolis is a resinous substance collected by honeybees and used in hive construction and maintenance. Cumulative evidence suggests that propolis may have anti-inflammatory, antibiotic, antioxidant, antihepatotoxic, and antitumor properties. In addition to topical applications, products containing propolis have been used increasingly as dietary supplements. Although reports of allergic reactions are not uncommon, propolis is reputed to be relatively nontoxic. Its systemic toxicity is rarely reported and hence may be underestimated. This is the first report of propolis-induced acute renal failure. A 59-year-old man required hemodialysis for acute renal failure. The patient had cholangiocarcinoma and had ingested propolis for 2 weeks before presentation. Renal function improved after propolis withdrawal, deteriorated again after reexposure, and then returned to a normal level after the second propolis withdrawal. This case indicates that propolis can induce acute renal failure and emphasizes the need for vigilance and care when propolis is used as a medicine or dietary supplement.

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We investigated the role of the beta chain HV4 region in the binding of a Vbeta10 T cell receptor to superantigen S. aureus enterotoxin C2 (SEC2)/MHC class II complexes. Residues 6971 of the Cw3/1.1 TCR Vbeta10 chain, derived from an H-2K(d)-restricted cytotoxic clone, were individually changed to alanine using site-directed mutagenesis, and mutated TCR beta chains were transfected along with the wild-type TCR alpha chain into a TCR alpha(-)beta(-) T hybridoma. SEC2/MHC recognition was measured by IL-2 production. Alanine substitutions in the HV4beta region, either did not affect (Ser69 and Lys71), or increased the recognition of SEC2/HLA-DR1 complex (Asp70), arguing against a general and direct role for the HV4beta region in superantigenrecognition. A theoretical-computational model of the SEC2/TCR Vbeta10 chain complex was constructed and predicted the presence of a unique salt bridge between Vbeta Asp30 and SEC2 Lys103. A perfect correlation was found between the likely presence of this salt bridge and the capacity of the HV4beta and previously obtained CDR1beta alanine mutants to induce an equal or greater response than the wild-type TCR.

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