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Context: Genetic variants in melanocortin 3 receptor (MC3R) and melanocortin 4 receptor (MC4R) genes are strongly associated with childhood obesity. Objective: This study aims to identify and functionally characterize MC3R and MC4R variants in an Asian cohort of children with severe earlyonset obesity. Methods: Whole-exome sequencing was performed to screen for MC3R and MC4R coding variants in 488 Asian children with severe earlyonset obesity (body mass index for age ≥97th percentile). Functionality of the identified variants were determined via measurement of intracellular cyclic adenosine monophosphate (cAMP) concentrations and luciferase activity. Results: Four MC3R and 2 MC4R heterozygous nonsynonymous rare variants were detected. There were 3 novel variants: MC3R c.151G > C (p.Val51Leu), MC4R c.127C > A (p.Gln43Lys), and MC4R c.272T > G (p.Met91Arg), and 3 previously reported variants: MC3R c.127G > A (p.Glu43Lys), MC3R c.97G > A (p.Ala33Thr), and MC3R c.437T > A (p.Ile146Asn). Both MC3R c.127G > A (p.Glu43Lys) and MC4R c.272T > G (p.Met91Arg) variants demonstrated defective downstream cAMP signaling activity. The MC4R c.127C > A (p.Gln43Lys) variant showed reduced cAMP signaling activity at low substrate concentration but the signaling activity was restored at high substrate concentration. The MC3R c.151G > C (p.Val51Leu) variant did not show a significant reduction in cAMP signaling activity compared to wild-type (WT) MC3R. Coexpression studies of the WT and variant MC3R/MC4R showed that the heterozygous variants did not exhibit dominant negative effect. Conclusion: Our functional assays demonstrated that MC3R c.127G > A (p.Glu43Lys) and MC4R c.272T > G (p.Met91Arg) variants might predispose individuals to early-onset obesity, and further studies are needed to establish the causative effect of these variants in the pathogenesis of obesity. [ABSTRACT FROM AUTHOR]

Context: Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear. Objective: To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D). Methods: Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater. Results: During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606). Conclusion: Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients. [ABSTRACT FROM AUTHOR]

Context: Early-onset diabetes has been associated with unfavorable cardiovascular risk but data on heart failure (HF) in this subpopulation are scarce. Objective: We aimed to study the risk of, and risk factors for, incident HF in individuals with early-onset type 2 diabetes. Methods: We studied 606 individuals with type 2 diabetes diagnosed before 40 years of age (early-onset) and 1258 counterparts with diabetes diagnosed from 41 to 65 years of age (usual-onset) with no HF history, at a regional hospital, over a median follow-up period of 7.1 years. Incident HF by European Cardiology Society criteria was determined. Results: A total of 62 and 108 HF events were identified in the early- and usual-onset groups (1.55 and 1.29 per 100 patient-years), respectively. Compared with usual-onset counterparts, individuals with early-onset diabetes had a 1.20-fold unadjusted (95% CI, 0.88-1.63; P = 0.26) and 1.91-fold age-adjusted (95% CI, 1.37-2.66; P < 0.001) hazard ratio (HR) for incident HF. Adjustment for traditional cardiometabolic risk factors only moderately mitigated the hazards (adjusted HR 1.69; 95% CI, 1.19-2.40; P = 0.003). However, additional adjustment for estimated glomerular filtration rate and albuminuria markedly attenuated the association of early-onset age with incident HF (adjusted HR 1.24; 95% CI, 0.87-1.77; P = 0.24). Notably, a long diabetes duration was not significantly associated with HF risk after accounting for kidney measures. Conclusion: Individuals with early-onset diabetes have at least the same absolute risk and a 2-fold age-adjusted relative risk for incident HF. Excess cardiorenal risk factors but not a long diabetes duration are main drivers for HF development in this diabetic population. [ABSTRACT FROM AUTHOR]

Context: Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain.Objectives: To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D.Design and Participants: We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater.Results: We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta P = 6.66 × 10-16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratio = 1.23, P = 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (P < 0.05).Conclusion: We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention. [ABSTRACT FROM AUTHOR]

In the accompanying paper, we described evolving a lipase to the point where variants were soluble, stable and capable of degrading C8 TAG and C8 esters. These variants were tested for their ability to survive in an environment that might be encountered in a washing machine. Unfortunately, they were inactivated both by treatment with a protease used in laundry detergents and by very low concentrations of sodium dodecyl sulfate (SDS). In addition, all the variants had very low levels of activity with triglycerides with long aliphatic chains and with naturally occurring oils, like olive oil. Directed evolution was used to select variants with enhanced properties. In the first 10 rounds of evolution, the primary screen was selected for variants capable of hydrolyzing olive oil whereas the secondary screen was selected for enhanced tolerance towards a protease and SDS. In the final six rounds of evolution, the primary and secondary screens identified variants that retained activity after treatment with SDS. Sixteen cycles of evolution gave variants with greatly enhanced lipolytic activity on substrates that had both long (C16 and C18) as well as short (C3 and C8) chains. We found variants that were stable for more than 3 hours in protease concentrations that rapidly degrade the wild-type enzyme. Enhanced tolerance towards SDS was found in variants that could break down naturally occurring lipid and resist protease attack. The amino acid changes that gave enhanced properties were concentrated in the cap domain responsible for substrate binding. [ABSTRACT FROM AUTHOR]

Vitellogenin (Vg) and vitellogenin receptor (VgR) play important roles in the vitellogenesis of insects. In this study, we cloned and characterized the two corresponding genes (TpVg and TpVgR) in an economically important insect, Thitarodes pui (Lepidoptera: Hepialidae), from the Tibetan plateau. The full length of TpVg is 5566 bp with a 5373 bp open reading frame (ORF) encoding 1,790 amino acids. Sequence alignment revealed that TpVg has three conserved domains: a Vitellogenin_N domain, a DUF1943 domain, and a von Willebrand factor type D domain (VWD). The full length of TpVgR is 5732 bp, with a 5397 bp ORF encoding 1798 amino acids. BLASTP showed that TpVgR belongs to the low-density lipoprotein receptor (LDLR) gene superfamily. Structural analysis revealed that TpVgR has a group of four structural domains: a ligand-binding domain (LBD), an epidermal growth factor (EGF)-precursor homology domain, a transmembrane (TM) domain, and a cytoplasmic domain. In addition, TpVgR has four cysteine-rich LDL repeats in the first ligand-binding site and seven in the second. Quantitative real-time polymerase chain reaction analysis revealed that the expression levels of TpVg and TpVgR are much higher in later pupa than in either the larval or adult stage, implying that the synthesis and uptake of Vg in T. pui occurs in the later pupal stage. These results will help us to understand the molecular mechanism of the reproductive capacity and will provide new insight into the mass rearing and utilization of T. pui. [ABSTRACT FROM AUTHOR]

Botryosphaeriaceae are an important fungal family that cause woody plant diseases worldwide. Recent studies have established a correlation between environmental factors and disease expression; however, less is known about factors that trigger these diseases. The current study reports on the 43.3Mb de novo genome of Lasiodiplodia theobromae and five other genomes of Botryosphaeriaceae pathogens. Botryosphaeriaceous genomes showed an expansion of gene families associated with cell wall degradation, nutrient uptake, secondary metabolism and membrane transport, which contribute to adaptations for wood degradation. Transcriptome analysis revealed that genes involved in carbohydrate catabolism, pectin, starch and sucrose metabolism, and pentose and glucuronate interconversion pathways were induced during infection. Furthermore, genes in carbohydrate-binding modules, lysine motif domain and the glycosyl hydrolase gene families were induced by high temperature. Among these genes, overexpression of two selected putative lignocellulase genes led to increased virulence in the transformants. These results demonstrate the importance of high temperatures in opportunistic infections. This study also presents a set of Botryosphaeriaceae-specific effectors responsible for the identification of virulence-related pathogen-associated molecular patterns and demonstrates their active participation in suppressing hypersensitive responses. Together, these findings significantly expand our understanding of the determinants of pathogenicity or virulence in Botryosphaeriaceae and provide new insights for developing management strategies against them. [ABSTRACT FROM AUTHOR]

In this secondary analysis of data from a double-blind randomized controlled trial carried out in northern China, we aimed to assess the effect of prenatal supplementation with multiple micronutrients (MMN) or iron + folic acid (IFA), versus folic acid (FA) alone, on risk of spontaneous preterm birth (SPB) and the impact of supplementation timing on SPB. A total of 18,775 nulliparous pregnant women enrolled between 2006 and 2009 were randomly assigned to receive daily FA, IFA, or MMN from the period before 20 weeks' gestation to delivery. The incidences of SPB for women consuming FA, IFA, and MMN were 5.7%, 5.6% and 5.1%, respectively. Compared with women given FA, the relative risks of SPB for those using MMN and IFA were 0.99 (95% confidence interval: 0.85, 1.16) and 0.89 (95% confidence interval: 0.79, 1.05), respectively. SPB incidence in women who started consuming FA, IFA, and MMN before the 12th week of gestation (4.6%, 4.2%, and 3.9%, respectively) was significantly reduced compared with starting supplement use on or after the 12th gestational week (6.9%, 7.2%, and 6.4%, respectively). Starting use of FA, IFA, or MMN supplements before the 12th week of gestation produced a 41%-45% reduction in risk of SPB. Early prenatal enrollment and micronutrient use during the first trimester of pregnancy appeared to be of particular importance for prevention of SPB, regardless of supplement group. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of plasmid-borne oqxAB genes on the development of fluoroquinolone resistance, mutations and bacterial fitness in Escherichia coli .Methods: MICs and mutation prevention concentrations were compared among E. coli strain TOP10 and two corresponding transformants harbouring the OqxAB-encoding plasmids. Mutants were selected by serial passages with the 0.5-fold MIC of ciprofloxacin, and were randomly selected to determine mutations. Bacterial fitness was evaluated by competition assays in vitro and in vivo .Results: The oqxAB -carrying plasmids contributed to a 4-8-fold increase in the ciprofloxacin MIC and increased the ciprofloxacin mutation prevention concentration by 8-16-fold. The MIC of ciprofloxacin for the two transformants increased faster than that of E. coli TOP10 by serial passaging. Novel mutations in gyrB (A468P or F458V) were first observed. Mutations in gyrA were distributed at codons 87 and 83 in the two transformants, whereas mutation A119E in gyrA dominated in the TOP10 mutants. Although the two oqxAB -bearing plasmids caused a decrease in fitness in vitro , their fitness increased when combined with more than one chromosomal mutation, and clear biological benefits were observed in vivo . The mutations in gyrB were associated with a fitness cost, which could be compensated for by additional mutations. The novel mutation gyrA ΔS83 significantly reduced biological fitness both in vitro and in vivo , and was thus quickly replaced by more beneficial mutations in the population.Conclusions: The possession of plasmid-borne oqxAB may facilitate the evolution of fluoroquinolone resistance, and the fitness cost of OqxAB-encoding plasmids could be compensated by additional chromosomal mutations. [ABSTRACT FROM AUTHOR]

Background: As a modulator of dopaminergic system, trace amine-associated receptor 1 has been shown to play a critical role in regulating the rewarding properties of additive drugs. It has been demonstrated that activation of trace amine-associated receptor 1 decreased the abuse-related behaviors of cocaine in rats. However, the role of trace amine-associated receptor 1 in specific stages of cocaine reward memory is still unclear. Methods: Here, using a cocaine-induced conditioned place preference model, we tested the effects of a selective trace amineassociated receptor 1 agonist RO5166017 on the expression, reconsolidation, and extinction of cocaine reward memory. Results: We found that RO5166017 inhibited the expression but not retention of cocaine-induced conditioned place preference. RO5166017 had no effect on the reconsolidation of cocaine reward memory. Pretreatment with RO5166017 before extinction hindered the formation of extinction long-term memory. RO5166017 did not affect the movement during the conditioned place preference test, indicating the inhibitory effect of RO5166017 on the expression of cocaine-induced conditioned place preference was not caused by locomotion inhibition. Using a cocaine i.v. self-administration model, we found that the combined trace amine-associated receptor 1 partial agonist RO5263397 with extinction had no effect on the following cue- and drug-induced reinstatement of cocaine-seeking behavior. Repeated administration of the trace amine-associated receptor 1 agonist during extinction showed a continually inhibitory effect on the expression of cocaine reward memory both in cocaine-induced conditioned place preference and cocaine self-administration models. Conclusions: Taken together, these results indicate that activation of trace amine-associated receptor 1 specifically inhibited the expression of cocaine reward memory. The inhibitory effect of trace amine-associated receptor 1 agonists on cocaine reward memory suggests that trace amine-associated receptor 1 agonists could be a promising agent to prevent cocaine relapse. [ABSTRACT FROM AUTHOR]

Background: The TLR/MyD88 signaling pathway is an important driver of inflammation and cancer and is a possible target for antitumor therapy.Methods: We generated a MyD88 inhibitor (TJ-M2010-5), which was designed to bind to the TIR domain of MyD88 to interfere with its homodimerization, and the TLR/MyD88 signal pathway. We utilized a mouse model of azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated cancer (CAC) in combination with TJ-M2010-5 administration to investigate the anti-inflammation-related cancer effect of MyD88 inhibitor in vivo. Data were analyzed with one-way and repeated measures analysis of variance. Differences in survival between groups were compared using the log rank test. All statistical tests were two-sided.Results: TJ-M2010-5 inhibited MyD88 homodimerization in transfected HEK293 cells in a concentration-dependent manner and suppressed MyD88 signaling in LPS-responsive RAW 264.7 cells in vitro. In a 10-week CAC mouse model (n = 30 per group), TJ-M2010-5 treatment statistically significantly reduced AOM/DSS-induced colitis and completely prevented CAC development with less related body mass loss, resulted in 0% mortality of treated mice (compared with 53% mortality of control mice), decreased cell proliferation, and increased apoptosis in colon tissue. TJ-M2010-5 treatment also inhibited production of inflammatory cytokines and chemokines (TNF-α, IL-6,G-CSF, MIP-1β, TGF-β1, IL-11, IL-17A, IL-22 and IL-23) and infiltration of immune cells (macrophages, dendritic cells, neutropihls and CD(+)4 T cells) in colon tissues of mice.Conclusions: Our findings suggest that TLR/MyD88 signaling may be a therapeutic target for CAC intervention and MyD88 inhibitors may be a promising therapeutic modality for treating patients with colitis or CAC. [ABSTRACT FROM AUTHOR]

The article presents a report on emergence of Escherichia coli co-producing New Delhi metallo-b-lactamase-1(NDM-1) and Klebsiella pneumoniae carbapenemase 2 (KPC-2) from a retail vegetable, China. Topics discussed include use of agar dilution method for determining of minimum inhibitory concentration of antimicrobial agents; its resistance to imipenem, ceftazidime, cefotaxime; and a table depicting characteristics of E. coli TS79e and its transconjugants.

Soybean pathogens significantly impact yield, resulting in over $4 billion dollars in lost revenue annually in the United States. Despite the deployment of improved soybean cultivars, pathogens continue to evolve to evade plant defense responses. Thus, there is an urgent need to identify and characterize gene networks controlling defense responses to harmful pathogens. In this review, we focus on major advances that have been made in identifying the genes and gene networks regulating defense responses with an emphasis on soybean-pathogen interactions that have been amenable to gene function analyses using gene silencing technologies. Further we describe new research striving to identify genes involved in durable broad-spectrum resistance. Finally, we consider future prospects for functional genomic studies in soybean and demonstrate that understanding soybean disease and stress tolerance will be expedited at an unprecedented pace. [ABSTRACT FROM AUTHOR]

Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200-4,100m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome of a Tibetan chicken and resequenced whole genomes of 32 additional chickens, including Tibetan chickens, village chickens, game fowl, and Red Junglefowl, and found that the Tibetan chickens could broadly be placed into two groups. Further analyses revealed that several candidate genes in the calcium-signaling pathway are possibly involved in adaptation to the hypoxia experienced by these chickens, as these genes appear to have experienced directional selection in the two Tibetan chicken populations, suggesting a potential genetic mechanism underlying high altitude adaptation in Tibetan chickens. The candidate selected genes identified in this study, and their variants, may be useful targets for clarifying our understanding of the domestication of chickens in Tibet, and might be useful in current breeding efforts to develop improved breeds for the highlands. [ABSTRACT FROM AUTHOR]

The larvae of Orthopygia glaucinalis (L.) (Lepidoptera: Pyralidae) are used to produce insect tea in Guizhou, China. We investigated the development and survival of O. glaucinalis reared on dried leaves of Platycarya strobilacea under laboratory conditions at 19, 22, 25, 28, 31, 34, and 37°C. The duration of development from egg deposition to adult emergence decreased significantly with increasing temperature from 19 to 31°C, whereas the duration of egg and overall development significantly increased at 34°C. Based on the extreme-value distribution function, the optimal temperature for survival of overall development was 24.89°C, and the larval stage was most susceptible to temperature extremes. The common linear model and the Ikemoto and Takai linear model were used to determine the relationship between temperature and the developmental rate, and estimated the low-temperature threshold (11.44 and 11.62°C, respectively) and the threshold constant (1220.70 and 1203.58 degree-days, respectively) of O. glaucinalis. Nonlinear models were used to assess in fitting the experiment data and to estimate the high temperature thresholds (34.00 to 39.08°C) and optimal temperatures (31.61 to 33.45°C). An intrinsic optimal temperature of 24.18°C was estimated for overall development using the Sharpe-Schoolfield-Ikemoto (SSI) model. Model-averaged parameter estimates and the unconditional standard error were also estimated for the temperature thresholds. Based on the biological parameters and model selection, we concluded that common linear, Lactin-1, and SSI models performed better for predicting the temperature-dependent development of O. glaucinalis. Our findings enable breeders to optimize the developmental rate of O. glaucinalis and improve the yield of insect tea. [ABSTRACT FROM AUTHOR]

Anti-Beauveria bassiana activity of aqueous fecal extracts from conventional German cockroaches [Blattella germanica (L.) ] was detected, but was not detected in samples from germ-free German cockroaches. Subsequently, bacterial strain BGI-14 was isolated from the gut of conventional German cockroaches and was identified as Pseudomonas reactans based on 16S rDNA sequence. The strain BGI-14 not only inhibited the germination of conidia, but also inhibited the growth of B. bassiana hyphae. Further studies demonstrated that B. bassiana infections in German cockroaches orally treated with the extracts of BGI-14 fermentation were significantly weakened. Compared with the control group, the cumulative mortality rate of treatment group was reduced by 10.3% at 20 d postinoculation. These studies imply that intestinal flora with anti-B. bassiana activity might contribute to resistance of infection by entomopathogenic fungi. [ABSTRACT FROM AUTHOR]

The 60-g subtropical Formosan leaf-nosed bat, Hipposideros terasensis, hibernates in the wild at warm roost (and hence body) temperatures up to 23°C. For small hibernators, torpid metabolic rate is temperature dependent and thus hibernation in warm hibernacula is predicted to be energetically costly. This species, however, rarely feeds during the hibernation season to offset the expected high energetic costs. In this study we used a respirometry system to quantify physiological characteristics of euthermic and torpid H. terasensis in winter. We tested the hypothesis that H. terasensis exhibits metabolic inhibition during torpor. Our results showed that H. terasensis saved 94.6% energy by using torpor at air temperatures of 15°C, compared with its euthermic metabolic rate at that air temperature. Torpor metabolic rate declined with declining air temperature to around 14°C, but then increased at lower air temperatures of 10-14°C. Above 14°C , the slope of 213.0°K ± 1.4°K between metabolic rates and body temperatures in an Arrhenius plot (or Q10 5 4.4) suggests that, in addition to direct temperature effects, H. terasensis exhibited metabolic inhibition during torpor. A model used to evaluate energy expenditure of H. terasensis showed that at 20°C and 23°C a 55-g bat needs 194 kJ (4.9 g fat) and 273.2 kJ (6.9 g fat), respectively, to survive a 70-day hibernation period. [ABSTRACT FROM AUTHOR]

Abscisic acid (ABA) regulates plant development and is crucial for plant responses to biotic and abiotic stresses. Studies have identified the key components of ABA signaling in Arabidopsis (Ambidopsis thaliana), some of which regulate ABA responses by the transcriptional regulation of downstream genes. Here, we report the functional identification of rice (Oryza sativa) ABI5-Like1 (ABL1), which is a basic region/leucine zipper motif transcription factor. ABL1 is expressed in various tissues and is induced by the hormones ABA and indole-3-acetic acid and stress conditions including salinity, drought, and osmotic pressure. The ABL1 deficiency mutant, abl1, shows suppressed ABA responses, and ABL1 expression in the Arabidopsis abi5 mutant rescued the ABA sensitivity. The ABL1 protein is localized to the nucleus and can directly bind ABA-responsive elements (ABREs; G-box) in vitro. A gene expression analysis by DNA chip hybridization confirms that a large proportion of down-regulated genes of abl1 are involved in stress responses, consistent with the transcriptional activating effects of ABLl. Further studies indicate that ABLl regulates the plant stress responses by regulating a series of ABRE-containing WRKY family genes. In addition, the abl1 mutant is hypersensitive to exogenous indole-3-acetic acid, and some ABRE-containing genes related to auxin metabolism or signaling are altered under ABL1 deficiency, suggesting that ABL1 modulates ABA and auxin responses by directly regulating the ABRE-containing genes. [ABSTRACT FROM AUTHOR]

Crop yield is most sensitive to water deficit during the reproductive stage. For rice, the most sensitive yield component is spikelet fertility and the most sensitive stage is immediately before heading. Here, we examined the effect of drought on the anther proteome of two rice genotypes: Moroberekan and IR64. Water was withheld for 3 d before heading (3DBH) in well watered controls for 5 d until the flag leaf relative water content (RWC) had declined to 45–50%. Plants were then re-watered and heading occurred 2–3 d later, representing a delay of 4–5 d relative to controls. The anther proteins were separated at 3 DBH, at the end of the stress period, and at heading in stressed/re-watered plants and controls by two-dimensional (2-D) gel electrophoresis, and 93 protein spots were affected reproducibly in abundance by drought during the experiment across two rice genotypes. After drought stress, upon re-watering, expressions of 24 protein spots were irreversible in both genotypes, 60 protein spots were irreversible in IR64 but reversible in Moroberekan, only nine protein spots were irreversible in Moroberekan while reversible in IR64. Among them, there were 14 newly drought-induced protein spots in IR64; none of them was reversible on re-watering. However, there were 13 newly drought-induced protein spots in Moroberekan, 10 of them were reversible on re-watering, including six drought-induced protein spots that were not reversed in IR64. Taken together, our proteomics data reveal that drought-tolerant genotype Moroberekan possessed better recovery capability following drought and re-watering at the anther proteome level than the drought-sensitive genotype IR64. The disruptions of drought to rice anther development and pollen cell functions are also discussed in the paper. [ABSTRACT FROM PUBLISHER]

The objective of this study was to compare the effects of Sanyinjiao (SP6), Xuanzhong (GB39), and an adjacent non-meridian point on menstrual pain and uterine arterial blood flow in primary dysmenorrhea patients. The design of the study was a prospective, randomized controlled trial. The setting of the study was the Shandong Institute of Medical Imaging, Jinan, China. The patients were 52 women with primary dysmenorrhea. Women received electroacupuncture (EA) at SP6 ( n = 13), GB39 ( n = 14), and an adjacent non-meridian point ( n = 12), respectively, for 10 minutes when scored ≥40 on a 100-mm visual analog scale (VAS), and for 30 minutes on the next 2 days. There was no EA in the waiting list group ( n = 13). Primary outcomes were menstrual pain, resistance index (RI), and the ratio between peak systolic to end-diastolic flow velocity (S/D) in uterine arteries. Secondary outcomes included verbal rating scale (VRS) and retrospective symptom scale (RSS). The SP6 group had a highly significant reduction in VAS scores compared with the waiting list group (−23.19 mm, 95% confidence interval [CI]−32.06 to −14.33, P < 0.0001), GB39 group (−18.58 mm, 95% CI −27.29 to −9.88, P < 0.0001) and the non-meridian point group (−20.78 mm, 95% CI −29.82 to −11.73, P < 0.0001), respectively. A significant reduction in VRS scores was found in the SP6 group compared with the GB39 group ( P = 0.034) and the non-meridian point group ( P = 0.038). There were no significant differences of RI, S/D-values and RSS scores among the four groups ( P > 0.05). EA at SP6 can immediately relieve menstrual pain and minimize the influence of pain on daily life compared with GB39 and an adjacent non-meridian point. The data preliminarily show the specificity of SP6 for the immediate pain relief of primary dysmenorrhea. [ABSTRACT FROM AUTHOR]

Escherichia coli isolates from diseased pigs were examined for antimicrobial susceptibility to 12 antimicrobials and possession of virulence genes (VGs), and then grouped according to the phylogenetic background and genetic relatedness. Associations between antimicrobial resistance (AMR) and VGs and between AMR and phylogenetic group were subsequently assessed. The results showed that most isolates (91%) were epidemiologically unrelated. Multiple antimicrobial-resistant phenotypes (≥5 antimicrobials) were observed in 89% of E. coli strains and the most frequent types of resistance were to sulfamethoxazole (95%), tetracycline (94%), chloramphenicol (89%), and streptomycin (84%). The majority of isolates belonged to phylogenetic group A (84%). The most prevalent VG was EAST1 (64%), followed by Stx2e (63%) and eae (47%). Resistance to ceftiofur was associated with the presence of certain VGs, whereas resistance to doxycycline and kanamycin was associated with the absence of certain VGs. These findings suggest that multidrug resistance phenotypes, a variety of VGs, and the clear associations between resistance and VGs are commonly present in E. coli strains from diseased pigs. These results indicate that there is a great need for surveillance programs in China to monitor AMR in pathogenic E. coli strains. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that geological or climatic events in the past triggered the radiative diversification of both animals and plants on islands as well as continents. The Qinghai–Tibetan Plateau (QTP) has been extensively uplifted since the Miocene, but there is little information on possible links between these events and biological diversification in this and adjacent regions. Partly to explore such links, we have examined the diversification of Saussurea (Asteraceae: Cardueae), a species-rich genus that is mostly endemic to QTP, but also occurs in arid highlands elsewhere in the Northern Hemisphere. The phylogenetic analyses were conducted on the basis of the nuclear (internal transcribed spacer, ITS) and plastid ( trnL-F and psbA-trnH) sequences from 55 species, representing 19 sections from all six subgenera of Saussurea, and species from 15 genera of the Cardueae. The results suggest that the currently circumscribed genus Saussurea ( s.l.) is a polyphyletic group and that five sections should be excluded from the genus. Samples from the other 14 sections (representing five subgenera) clustered as a monophyletic group (here designated the Saussurea s.s. lineage, SSSL) with high statistical support. However, none of the analyses (nuclear, plastid or combined) resolved SSSL's infrageneric phylogeny, and the parallel clades of the lineage indicate that island-like adaptive radiation occurred. Furthermore, this radiation appears to have occurred 14–7 Mya, during the period of the major uplift events of QTP. Thus, our results support the hypothesis that geological events may play important roles in driving biological diversification through continental radiation. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 97, 893–903. [ABSTRACT FROM AUTHOR]

Stresses leading to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) elicit a highly conserved ER stress response in plants called the unfolded protein response (UPR). While the response itself is well documented in plants, the components of the signaling pathway are less well known. We have identified three membrane-associated basic domain/ leucine zipper (bZlP) factors in Arabidopsis thaliana that are candidates for ER stress sensors/transducers. One of these factors, bZlP28, an ER-resident transcription factor, is activated in response to treatment by tunicamycin (TM), an agent that blocks N-linked protein glycosylation. Following TM treatment, bZlP28 is processed, releasing its N-terminal, cytoplasm-facing domain, which is translocated to the nucleus. Expression of a truncated form of bZlP28, containing only the cytoplasmic domain of the protein, upregulated the expression of ER stress response genes in the absence of stress conditions. Thus, bZlP28 serves as a sensor/transducer in Arabidopsis to mediate ER stress responses related to UPR. [ABSTRACT FROM AUTHOR]

Virus-induced cytoplasmic inclusion bodies (referred to as virus replication complexes [VRCs]) consisting of virus and host components are observed in plant cells infected with tobacco mosaic virus, but tile components that modulate their form and function are not fully understood. Here, we show that the tobacco mosaic virus 126-kD protein fused with green fluorescent protein formed cytoplasmic bodies (126-bodies) in the absence of other viral components. Using mutant 126-kD:green fluorescent fusion proteins and viral constructs expressing the corresponding mutant 126-kD proteins, it was determined that tile size of the 126-bodies and the corresponding VRCs changed in synchrony for each 126-kD protein mutation tested. Through colabeling experiments, we observed the coalignment and intracellular trafficking of 126-bodies and, regardless of size, VRCs, along microfilaments (MFs). Disruption of MFs with MF-depolymerizing agents or through virus-induced gene silencing compromised the intracellular trafficking of the 126-bodies and VRCs and virus cell-to-cell movement, but did not decrease virus accumulation to levels that would affect virus movement or prevent VRC formation. Our results indicate that (1) the 126-kD protein modulates VRC size and traffics along MFs in cells; (2) VRCs traffic along MFs in cells, possibly through an interaction with the 126-kD protein, and the negative effect of MF antagonists on 126-body and VRC intracellular movement and virus cell-to-cell movement correlates with the disruption of this association; and (3) virus movement was not correlated with VRC size. [ABSTRACT FROM AUTHOR]

A new species ofSaussurea,S. erectaS. W. Liu, J. T. Pan&J. Q. Liusp. nov., is described from Tibet. It resemblesS. kingiibut may be distinguished by having distinct stems and glabrous achenes.Saussurea kingiiwas placed in sect.Pseudoeriocoryneof subgen.Eriocoryne; this section was circumscribed by acaulescence and an inflorescence with congested capitula surrounded by a rosette of leaves. The discovery ofS. erectawith distinct stems, cauline leaves and corymbose capitula blurred the delimitation of sect.Pseudoeriocoryneand suggested that the section may be polyphyletic. Both the close relationship and the significant difference betweenS. erectaandS. kingiiwere confirmed by analyses of nrDNA ITS sequences. The resulting phylogenies based on ITS data further suggest thatSaussureasect.Pseudoeriocoryne, as traditionally defined, does not constitute a monophyletic group. The rapid radiation and speciation ofSaussureain the Qinghai-Tibetan Plateau, as inferred from ITS phylogeny, are discussed. © 2005 The Linnean Society of London,Botanical Journal of the Linnean Society, 2005,147, 349–356. [ABSTRACT FROM AUTHOR]

Heparin/heparan sulfate interacting protein (HIP, also known as ribosome protein L29) is involved in cell–cell and cell–extracelluar matrix interactions and influences cell proliferation, migration and differentiation. In the present study, we investigated the role of HIP in anticancer drug-induced apoptosis. Both colon cancer HCT-116 and HT-29 cells showed dose-dependent down-regulation of HIP expression when treated with sodium butyrate. The down-regulation was negatively correlated with the percentage of apoptotic cells (R = −0.955, P = 0.03 and R = −0.792, P = 0.06 for HCT-116 and HT-29 cells, respectively). The correlation between HIP expression and apoptosis in HCT-116 cells was also evident in the differential expression of HIP in the floating and adherent cell populations. Most apoptotic cells were distributed in the floating population. HIP expression in this population was ∼30% lower than adherent and untreated control cells. HIP expression in HCT-116 cells was also significantly decreased in parallel with apoptosis after treatment with 50 µM camptothecin and 20 µM 5-fluorouracil. This indicates that the down-regulation of HIP may be a general phenomenon in anticancer drug-induced apoptosis. The down-regulation of HIP occurred in the early phase of apoptosis, in parallel with the activation of caspase-3 and the externalization of phosphatidylserine. The functional significance of HIP in apoptosis was shown by knocking down the expression of HIP using small interfering RNA. A 50% reduction in HIP expression was sufficient to increase the percentage of apoptotic cells (from 11 to 20%) and increase the sensitivity of the cells to apoptosis induced by 1 mM butyrate by 60%. These results indicate that HIP may play an important role in anticancer drug-induced apoptosis. [ABSTRACT FROM AUTHOR]

Ligularia , a highly diversified genus in the eastern Qinghai–Tibet Plateau and adjacent areas, was chosen as a suitable subject in which to study speciation patterns in this ‘hot spot’ area at the chromosomal level. Chromosome numbers and karyotypes were studied in 23 populations of 14 species, most of which are endemic to this area. The basic number x = 29 was confirmed for all species. Ligularia virgaurea was found to have diploid and triploid cytotypes, 2 n = 58 and 87. Other species are only diploid, with 2 n = 58. The karyotypes of all populations within any species, and all species spanning most sections and covering most of the morphological range in Ligularia , are very similar to each other, belonging to type 2A according to Stebbin's classification. This karyotype was also found in its close allies, e.g. Cremanthodium , Ligulariopsis , Parasenecio , and Sinacalia . Aneuploid reduction of chromosome number from 2 n = 60 to 58 and karyotypic variation was found in Ligularia and its allies. Such a chromosomal pattern with few polyploids infers that variation of karyotype structure at the diploid level seems to be the predominant feature of chromosomal evolution in this group and sympatric speciation via hybridization and polyploidization has played a minor role in its species diversity. © 2004 The Linnean Society of London, Botanical Journal of the Linnean Society , 2004, 144 , 329–342. [ABSTRACT FROM AUTHOR]

The mechanism underlying ethanol-induced apoptosis in liver cells is not clear. Sphingomyelin (SM) metabolism is a novel signal transduction pathway that has an impact on apoptosis in many cell types. We investigated whether the SM pathway is involved in ethanol-induced apoptosis in the liver. Hep G2 cells were treated with ethanol followed by assaying apoptosis, sphingomyelinase (SMase) activity, caspase-3 activity, and the changes of SM content in the cells. We found that ethanol dose-dependently increased apoptosis and the effect was accompanied by increases of caspase-3 activity and neutral SMase activity. At concentrations of 80 and 160 mM, ethanol significantly increased caspase-3 activity by 120% and neutral SMase activity by 24%. The activity of acid SMase was only slightly increased without statistical significance. C2-ceramide, the exogenous SM metabolite, mimicked the effects of ethanol on apoptosis and caspase-3 activation. When the SM content was determined 24 h after treatment with ethanol, its level was 15% lower than that of controls. The results indicate that metabolism of SM triggered by neutral SMase participates in ethanol-induced apoptosis in Hep G2 cells and activation of caspase-3 is involved in the apoptotic pathway. [ABSTRACT FROM PUBLISHER]

Neotoxoptera formosana (Takahashi), the onion aphid, is an oligophagous pest that mainly feeds on plants from the Allium genus. It sucks nutrients from the plants and indirectly acts as a vector for plant viruses. This aphid causes severe economic losses to Allium tuberosum agriculture in China. To better understand the host plant specificity of N. formosana on Allium plants and provide essential information for the control of this pest, we generated the entire genome using Pacific Biosciences long-read sequencing and Hi-C data. Six chromosomes were assembled to give a final size of 372.470Mb, with an N50 scaffold of 66.911Mb. The final draft genome assembly, from 192Gb of raw data, was approximately 371.791Mb in size, with an N50 contig of 24.99 Kb and an N50 scaffold of 2.637Mb. The average GC content was 30.96%. We identified 73Mb (31.22%) of repetitive sequences, 14,175 protein-coding genes, and 719 noncoding RNAs. The phylogenetic analysis showed that N. formosana and Pentalonia nigronervosa are sister groups. We found significantly expanded gene families that were involved in the THAP domain, the DDE superfamily endonuclease, zinc finger, immunity (ankyrin repeats), digestive enzyme (serine carboxypeptidase) and chemosensory receptor. This genome assembly could provide a solid foundation for future studies on the host specificity of N. formosana and pesticide-resistant aphid management. [ABSTRACT FROM AUTHOR]

The article offers the author's view on the succesful strategies for the nanowire assemblies ordering in China.

The article presents information on the herpes zoster vaccination in the people of age between 50 and 59 Years. It states that Herpes zoster caused by reactivation of latent varicella-zoster virus (VZV) in the dorsal root or cranial nerve ganglia manifests as unilateral acute pain accompanied by a vesicular rash. It also states that the U.S. Food and Drug Administration (FDA) approved Zostavax in 2006 to prevent shingles. Demonstration of the efficacy of Zostavax is also discussed.

Objectives To investigate the occurrence of 16S rRNA methylases conferring high-level resistance to aminoglycosides in Enterobacteriaceae isolated from two pig farms in China. Methods Enterobacteriaceae isolated from 151 pig rectal swab samples and 9 environmental samples were screened for the presence of the rmtA, rmtB, armA and rmtC genes by PCR and sequencing. Conjugation experiments were carried out to study the transferability of the 16S rRNA methylase genes. All isolates and their transconjugants were tested for susceptibility to antimicrobial agents. The clonal relatedness of RmtB-producing Escherichia coli was assessed by PFGE with XbaI. Results Of 152 Enterobacteriaceae isolates recovered from pigs, 49 (32%) were positive for the rmtB gene, including 48 E. coli and a single isolate of Enterobacter cloacae. Of the nine Enterobacteriaceae isolates from environmental samples, no 16S rRNA methylase gene was identified. The 49 rmtB-positive isolates showed resistance to ampicillin, tetracycline and trimethoprim and also carried a blaTEM gene. Transfer of the rmtB and blaTEM genes by conjugation experiments of all 49 isolates was successful, suggesting that the rmtB-containing plasmids in the E. coli and E. cloacae isolates were self-transmissible. Conjugative transfer frequencies varied from 2.2 × 10−10 to 1.3 × 10−6 transconjugants per recipient. The transfer of non-aminoglycoside antimicrobial resistance traits was also observed in most cases. Forty-four rmtB-positive E. coli showed 30 different PFGE types. Conclusions The rmtB gene was detected on conjugative plasmids of porcine E. coli and E. cloacae isolates. Both horizontal gene transfer and clonal spread were responsible for the dissemination of the rmtB gene. The emergence of 16S rRNA methylases in Enterobacteriaceae isolates is described for the first time in China. This is also the first report of rmtB-positive Enterobacteriaceae among healthy food-producing animals. [ABSTRACT FROM AUTHOR]

Background and Aims It is an enduring question as to the mechanisms leading to the high diversity and the processes producing endemics with unusual morphologies in the Himalayan alpine region. In the present study, the phylogenetic relationships and origins of three such endemic genera were analysed, Dolomiaea, Diplazoptilon and Xanthopappus, all in the tribe Cardueae of Asteraceae. Methods The nuclear rDNA internal transcribed spacer (ITS) and plastid trnL-F and psbA-trnH regions of these three genera were sequenced. The same regions for other related genera in Cardueae were also sequenced or downloaded from GenBank. Phylogenetic trees were constructed from individual and combined data sets of the three types of sequences using maximum parsimony, maximum likelihood and Bayesian analyses. Key Results The phylogenetic tree obtained allowed earlier hypotheses concerning the relationships of these three endemic genera based on gross morphology to be rejected. Frolovia and Saussurea costus were deeply nested within Dolomiaea, and the strong statistical support for the Dolomiaea–Frolovia clade suggested that circumscription of Dolomiaea should be more broadly redefined. Diplazoptilon was resolved as sister to Himalaiella, and these two together are sister to Lipschitziella. The clade comprising these three genera is sister to Jurinea, and together these four genera are sister to the Dolomiaea–Frolovia clade. Xanthopappus, previously hypothesized to be closely related to Carduus, was found to be nested within a well-supported but not fully resolved Onopordum group with Alfredia, Ancathia, Lamyropappus, Olgaea, Synurus and Syreitschikovia, rather than the Carduus group. The crude dating based on ITS sequence divergence revealed that the divergence time of Dolomiaea–Frolovia from its sister group probably occurred 13·6–12·2 million years ago (Ma), and the divergence times of the other two genera, Xanthopappus and Diplazoptilon, from their close relatives around 5·7–4·7 Ma and 2·0–1·6 Ma, respectively. Conclusions The findings provide an improved understanding of the intergeneric relationships in Cardueae. The crude calibration of lineages indicates that the uplifts of the Qiinghai–Tibetan Plateau since the Miocene might have served as a continuous stimulus for the production of these morphologically aberrant endemic elements of the Himalayan flora. [ABSTRACT FROM AUTHOR]

With the broad application of genomic information, SNP-based measures of estimating inbreeding have been widely used in animal breeding, especially based on runs of homozygosity. Inbreeding depression is better estimated by SNP-based inbreeding coefficients than pedigree-based inbreeding in general. However, there are few comprehensive comparisons of multiple methods in pigs so far, to some extent limiting their application. In this study, to explore an appropriate strategy for estimating inbreeding depression on both growth traits and reproductive traits in a Large White pig population, we compared multiple methods for the inbreeding coefficient estimation based on both pedigree and genomic information. This pig population for analyzing the influence of inbreeding was from a pig breeding farm in the Inner Mongolia of China. There were 26,204 pigs with records of age at 100 kg (AGE) and back-fat thickness at 100 kg (BF), and 6,656 sows with reproductive records of the total number of piglets at birth (TNB), and the number of alive piglets at birth (NBA), and litter weight at birth. Inbreeding depression affected growth and reproductive traits. The results indicated that pedigree-based and SNP-based inbreeding coefficients had significant effects on AGE, TNB, and NBA, except for BF. However, only SNP-based inbreeding coefficients revealed a strong association with inbreeding depression on litter weight at birth. Runs of homozygosity-based methods showed a slight advantage over other methods in the correlation analysis of inbreeding coefficients and estimation of inbreeding depression. Furthermore, our results demonstrated that the model-based approach (RZooRoH) could avoid miscalculations of inbreeding and inbreeding depression caused by inappropriate parameters, which had a good performance on both AGE and reproductive traits. These findings might improve the extensive application of runs of homozygosity analysis in pig breeding and breed conservation. [ABSTRACT FROM AUTHOR]

With the development of high-throughput genotyping techniques, selection signatures in the genome of domestic pigs have been extensively interrogated in the last decade. The Duroc, a major commercial pig breed famous for its fast growth rate and high lean ratio, has not been extensively studied focusing on footprints of intensively artificial selection in their genomes by a lot of re-sequencing data. The goal of this study was to investigate genomic regions under artificial selection and their contribution to the unique phenotypic traits of the Duroc using whole-genome resequencing data from 97 pigs. Three complementary methods (di, CLR, and iHH12) were implemented for selection signature detection. In Total, 464 significant candidate regions were identified, which covered 46.4 Mb of the pig genome. Within the identified regions, 709 genes were annotated, including 600 candidate protein-coding genes (486 functionally annotated genes) and 109 lncRNA genes. Genes undergoing selective pressure were significantly enriched in the insulin resistance signaling pathway, which may partly explain the difference between the Duroc and other breeds in terms of growth rate. The selection signatures identified in the Duroc population demonstrated positive pressures on a set of important genes with potential functions that are involved in many biological processes. The results provide new insights into the genetic mechanisms of fast growth rate and high lean mass, and further facilitate follow-up studies on functional genes that contribute to the Duroc’s excellent phenotypic traits. [ABSTRACT FROM AUTHOR]

Polyinosinic-polycytidylic acid (poly I:C), a synthetic dsRNA analog, has been demonstrated to have stimulatory effects similar to viral dsRNA. To gain deep knowledge of the host transcriptional response of pigs to poly I:C stimulation, in the present study, we cultured and stimulated peripheral blood mononuclear cells (PBMC) of piglets of one Chinese indigenous breed (Dapulian) and one modern commercial breed (Landrace) with poly I:C, and compared their transcriptional profiling using RNA-sequencing (RNA-seq). Our results indicated that poly I:C stimulation can elicit significantly differentially expressed (DE) genes in Dapulian (g = 290) as well as Landrace (g = 85). We also performed gene set analysis using the Gene Set Enrichment Analysis (GSEA) package, and identified some significantly enriched gene sets in Dapulian (g = 18) and Landrace (g = 21). Most of the shared DE genes and gene sets were immune-related, and may play crucial rules in the immune response of poly I:C stimulation. In addition, we detected large sets of significantly DE genes and enriched gene sets when comparing the gene expression profile between the two breeds, including control and poly I:C stimulation groups. Besides immune-related functions, some of the DE genes and gene sets between the two breeds were involved in development and growth of various tissues, which may be correlated with the different characteristics of the two breeds. The DE genes and gene sets detected herein provide crucial information towards understanding the immune regulation of antiviral responses, and the molecular mechanisms of different genetic resistance to viral infection, in modern and indigenous pigs. [ABSTRACT FROM AUTHOR]

As a major component of genomic variation, copy number variations (CNVs) are considered as promising markers for some phenotypic and economically important traits in domestic animals. Using a custom-designed 1M array CGH (aCGH), we performed CNV discovery in 12 pig samples from one Asian wild boar population, six Chinese indigenous breeds, and two European commercial breeds. In total, we identified 758 CNV regions (CNVRs), covering 47.43 Mb of the pig genome sequence. Of the total porcine genes, 1295 genes were completely or partially overlapped with the identified CNVRs, which enriched in the terms related to sensory perception of the environment, neurodevelopmental processes, response to external stimuli, and immunity. Further probing the potential functions of these genes, we also found a suite of genes related important traits, which make them a promising resource for exploring the genetic basis of phenotype differences among diverse pig breeds. Compared with previous relevant studies, the current study highlights that different platforms can complement each other, and the combined implementation of different platforms is beneficial to achieve the most comprehensive CNV calls. CNVs detected in diverse populations herein are essentially complementary to the CNV map in the pig genome, which would be helpful for understanding the pig genome variants and investigating the associations between various phenotypes and CNVs. [ABSTRACT FROM AUTHOR]