Control of grain size in rice by TGW3 phosphorylation of OsIAA10 through potentiation of OsIAA10-OsARF4-mediated auxin signaling.

Grain size is a key component of grain yield and quality in crops. Several core players of auxin signaling have been revealed to modulate grain size; however, to date, few genetically defined pathways have been reported, and whether phosphorylation could boost degradation of Aux/IAA proteins is uncertain. Here, we show that TGW3 (also called OsGSK5) interacts with and phosphorylates OsIAA10. Phosphorylation of OsIAA10 facilitates its interaction with OsTIR1 and subsequent destabilization, but this modification hinders its interaction with OsARF4. Our genetic and molecular evidence identifies an OsTIR1-OsIAA10-OsARF4 axis as key for grain size control. In addition, physiological and molecular studies suggest that TGW3 mediates the brassinosteroid response, the effect of which can be relayed through the regulatory axis. Collectively, these findings define a auxin signaling pathway to regulate grain size, in which phosphorylation of OsIAA10 enhances its proteolysis and potentiates OsIAA10-OsARF4-mediated auxin signaling.

Association between gestational diabetes mellitus and preterm birth subtypes / 中华流行病学杂志

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

The directionality of measurement bias: a directed acyclic graph-based structural perspective / 中华流行病学杂志

Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.

Proportion and rate: connotation and understanding route / 中华流行病学杂志

Proportion and rate have multiple and overlapping meanings, which blur their concepts. Based on the existence of the states and the occurrence of the events and their measuring process, we first put forward the concept of "cumulative number of states in point time". Considering the general meaning of "rate" in mathematics and the units of the elements in indexes, this paper puts forward the concept of "the change of cumulative number of states in point time", which is equal to the commonly acknowledged concept "number of incident event within observation period" or "absolute rate", and further constructs relative rate and proportion. Proportions can be classified into three types: time-point (or rate-type) constitutional proportion, time-period incidence proportion and their synthesis, time-period constitutional proportion. The essential difference between relative rate and time-period proportions is whether the observation period is regarded as a one-unit-length fixed period which would be further moved to the description of the indexes. Furthermore, the sources populations of relative rate and proportions are exclusively those at the beginning of the observation period. Thus, we established a unified identification route about ratios, proportions, and rates, the basic indicators of categorical data in populations. These are applicable to both fixed and dynamic populations. The paper aims to clarify the connotation of the indexes and the feasible understanding route and provide some reference for the population researchers.

Verification and dissection of one quantitative trait locus for grain size and weight on chromosome 1 in rice.

Grain size and weight are the key traits determining rice quality and yield and are mainly controlled by quantitative trait loci (QTL). In this study, one minor QTL that was previously mapped in the marker interval of JD1009-JD1019 using the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population, qTGW1-2, was validated to regulate grain size and weight across four rice-growing seasons using twenty-one near isogenic line (NIL)-F2 populations. The twenty-one populations were in two types of genetic background that were derived from the same parents HHZ and JZ1560. Twelve F9, F10 or F11 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were developed from one residual heterozygote (RH) in the HHZ/JZ1560 RIL population, and the remaining nine BC3F3, BC3F4 or BC3F5 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were constructed through consecutive backcrosses to the recurrent parent HHZ followed with marker assistant selection in each generation. Based on the QTL analysis of these genetic populations, qTGW1-2 was successfully confirmed to control grain length, width and weight and further dissected into two QTLs, qTGW1-2a and qTGW1-2b, which were respectively narrowed down to the marker intervals of JD1139-JD1127 (~ 978.2-kb) and JD1121-JD1102 (~ 54.8-kb). Furthermore, the two types of NIL-F2 populations were proved to be able to decrease the genetic background noise and increase the detection power of minor QTL. These results provided an important basis for further map-based cloning and molecular design breeding with the two QTLs in rice.

Identification of qLG2, qLG8, and qWG2 as novel quantitative trait loci for grain shape and the allelic analysis in cultivated rice.

MAIN CONCLUSION: Three novel QTLs for grain shape were genetically fine mapped, with two of which to a 250-kb target interval on rice chromosome 2 that contains fourteen candidate genes. Grain shape (grain length, width, and thickness) determines crop yield and grain quality. However, the trait is regulated by numerous naturally occurring quantitative trait loci (QTLs) and the underlying mechanism remains largely unknown. Here, we report the genetic mapping of three new QTLs, qLG2, qWG2, and qLG8 that each exerts a semi-dominant effect on grain shape in cultivated rice. These QTLs were validated using populations derived from the corresponding chromosome segment substitution lines (CSSLs), and were further delimited to small genomic intervals in progeny testing experiments. Especially, qLG2/qWG2 was placed into an about 250-kb genomic candidate region, and 14 predicted ORFs localized within the interval. We also evaluated the individual and pyramiding genetic effect(s) of these QTL(s) using the corresponding nearly isogenic lines, and found that they have additive effects on the traits. Collectively, these findings provided useful information as a tool to improve grain shape in crop breeding programs and established foundations for future QTL cloning.

Genome-Wide Identification of QTLs for Grain Protein Content Based on Genotyping-by-Resequencing and Verification of qGPC1-1 in Rice.

To clarify the genetic mechanism underlying grain protein content (GPC) and to improve rice grain qualities, the mapping and cloning of quantitative trait loci (QTLs) controlling the natural variation of GPC are very important. Based on genotyping-by-resequencing, a total of 14 QTLs were detected with the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population in 2016 and 2017. Seven of the fourteen QTLs were repeatedly identified across two years. Using three residual heterozygote-derived populations, a stably inherited QTL named as qGPC1-1 was validated and delimited to a ~862 kb marker interval JD1006-JD1075 on the short arm of chromosome 1. Comparing the GPC values of the RIL population determined by near infrared reflectance spectroscopy (NIRS) and Kjeldahl nitrogen determination (KND) methods, high correlation coefficients (0.966 and 0.983) were observed in 2016 and 2017. Furthermore, 12 of the 14 QTLs were identically identified with the GPC measured by the two methods. These results indicated that instead of the traditional KND method, the rapid and easy-to-operate NIRS was suitable for analyzing a massive number of samples in mapping and cloning QTLs for GPC. Using the gel-based low-density map consisted of 208 simple sequence repeat (SSR) and insert/deletion (InDel) markers, the same number of QTLs (fourteen) were identified in the same HHZ/JZ1560 RIL population, and three QTLs were repeatedly detected across two years. More stably expressed QTLs were identified based on the genome resequencing, which might be attributed to the high-density map, increasing the detection power of minor QTLs. Our results are helpful in dissecting the genetic basis of GPC and improving rice grain qualities through molecular assisted selection.

New cases are they incident or newly discovered / 中华疾病控制杂志

@#New case is a basic concept in epidemiology and often serves as the numerator for the indexes of the frequency of disease in a population． However，the exact definition of new case is still un- clear． Based on the natural history of disease combined with the concept of event-state，this article rede- fines case-related concepts and compares them with traditional concepts． The study found that the so- called new cases in traditional epidemiological studies are actually the cases firstly discovered，including newly discovered cases and identifiable newly incident cases ( disease initiation) ． In the real world，new cases are often difficult to measure，and together with the continuous process of disease development and iceberg phenomenon，those may affect the accuracy of disease frequency measurement and causal infer- ence． A correct understanding of the meaning of case-related concepts，the meanings they reflect，and the differences between them help to rationally interpret the results of epidemiological research．

Advances in research of application of low-temperature plasma in microbiology / 上海预防医学

Low-temperature plasma has special physicochemical properties that can cause inactivation and mutation of microorganisms through complex biochemical processes.This article reviews the application of low-temperature plasma in microbiology, including sterilization, screening of bacterial strains, and antibacterial treatment.It also discussed the current research status and existing problems to provide ideas for promoting the development of interdisciplinary collaboration in low-temperature plasma reserch.

Detection bias:structural analysis of different study designs / 上海预防医学

Detection bias is an information bias.It was first proposed by Horwitz from the study investigating the association of the administration of estrogen after menopause with the occurrence of endometrial cancer, which still prevails in most epidemiological studies.We use the Directed Acyclic Graph to analyze the effect of a given exposure on a specific outcome with the association estimates between the measured exposure and outcome.Detection bias occurs when there is additional open paths irrelevant to the target path of interest which is originated from measured exposure to measured outcome.We further analyzed how the detection bias was formed under different study designs, including cohort study, randomized clinical trial and case-control study in order to further investigate its potential influence on the effect/association estimation.

Detection bias:structural analysis of different study designs / 上海预防医学

Detection bias is an information bias.It was first proposed by Horwitz from the study investigating the association of the administration of estrogen after menopause with the occurrence of endometrial cancer, which still prevails in most epidemiological studies.We use the Directed Acyclic Graph to analyze the effect of a given exposure on a specific outcome with the association estimates between the measured exposure and outcome.Detection bias occurs when there is additional open paths irrelevant to the target path of interest which is originated from measured exposure to measured outcome.We further analyzed how the detection bias was formed under different study designs, including cohort study, randomized clinical trial and case-control study in order to further investigate its potential influence on the effect/association estimation.

Dissection of three quantitative trait loci for grain size on the long arm of chromosome 10 in rice (Oryza sativa L.).

BACKGROUND: Thousand grain weight is a key component of grain yield in rice, and a trait closely related to grain length (GL) and grain width (GW) that are important traits for grain quality. Causal genes for 16 quantitative trait loci (QTL) affecting these traits have been cloned, but more QTL remain to be characterized for establishing a genetic regulating network. A QTL controlling grain size in rice, qGS10, was previously mapped in the interval RM6100-RM228 on chromosome 10. This study aimed to delimitate this QTL to a more precise location. METHOD: A total of 12 populations were used. The ZC9 population comprised 203 S 1:2 families derived from a residual heterozygous (RH) plant in the F 9 generation of the indica rice cross Teqing (TQ)/IRBB52, segregating the upper region of RM6100-RM228 and three more regions on chromosomes 1, 9, and 11. The Ti52-1 population comprised 171 S 1 plants derived from one RH plant in F 7 of TQ/IRBB52, segregating a single interval that was in the lower portion of RM6100-RM228. The other ten populations were all derived from Ti52-1, including five S 1 populations with sequential segregating regions covering the target region and five near isogenic line (NIL) populations maintaining the same segregating pattern. QTL analysis for 1,000-grain weight, GL, and GW was performed using QTL IciMapping and SAS procedure GLM. RESULT: Three QTL were separated in the original qGS10 region. The qGL10.1 was located in the upper region RM6704-RM3773, shown to affect GL only. The qGS10.1 was located within a 207.1-kb interval flanked by InDel markers Te20811 and Te21018, having a stable and relatively high effect on all the three traits analyzed. The qGS10.2 was located within a 1.2-Mb interval flanked by simple sequence repeat markers RM3123 and RM6673. This QTL also affected all the three traits but the effect was inconsistent across different experiments. QTL for grain size were also detected in all the other three segregating regions. CONCLUSION: Three QTL for grain size that were tightly linked on the long arm of chromosome 10 of rice were separated using NIL populations with sequential segregating regions. One of them, qGS10.1, had a stable and relatively high effect on grain weight, GL, and GW, providing a good candidate for gene cloning. Another QTL, qGS10.2, had a significant effect on all the three traits but the effect was inconsistent across different experiments, providing an example of genotype-by-environmental interaction.

Natural variation at qHd1 affects heading date acceleration at high temperatures with pleiotropism for yield traits in rice.

BACKGROUND: Rice is highly sensitive to temperature fluctuations. Recently, the frequent occurrence of high temperature stress has heavily influenced rice production. Proper heading date in specific environmental conditions could ensure high grain yield. Rice heading greatly depends on the accurate measurement of environmental changes, particularly in day length and temperature. In contrary to the detailed understanding of the photoperiod pathway, little has been known about how temperature regulates the genetic control of rice heading. RESULTS: Near isogenic lines that were segregated for qHd1, were developed from a cross between indica rice varieties Zhenshan 97 (ZS97) and Milyang 46 (MY46). Using a five sowing-date experiment in the paddy field, we observed the involvement of qHd1 in temperature responses. With the gradual increase of temperature from Trial I to V, heading date of MY46 homozygotes continued to decrease for about 5 d per trial from 76 to 58 d, while that of ZS97 homozygotes was promoted at the same rate from Trial I to III and then stabilized at 69 d. This thermal response was confirmed in a temperature-gradient experiment conducted in the phytotron. It is also found that tolerance of the ZS97 allele to heading acceleration at high temperature was associated with higher grain weight that resulted in higher grain yield. Then, by qRT-PCR and RNA-seq, we found the pathway OsMADS51-Ehd1-RFT1/Hd3a underlying the qHd1-mediated floral response to temperature. By sequence comparison, OsMADS51 for qHd1 displayed a 9.5-kb insertion in the 1st intron of the ZS97 allele compared to the MY46 allele. Furthermore, this large insertion is commonly found in major early-season indica rice varieties, but not in the middle- and late-season ones, which corresponds to the requirement for high-temperature tolerance during the heading and grain-filling stages of early-season rice. CONCLUSIONS: Beneficial alleles at qHd1 confer tolerance to high temperatures at the heading and grain-filling stages, playing a significant role in the eco-geographical adaptation of early-season indica rice during modern breeding. These results, together with the underlying OsMADS51-Ehd1-RFT1/Hd3a floral pathway, provide valuable information for better understanding the molecular mechanism of temperature responsive regulation of heading date and yield traits in rice.

Rice Flowering Locus T 1 plays an important role in heading date influencing yield traits in rice.

Important role of flowering genes in enhancing grain productivity in rice has become well recognized for a number of key genes regulating the florigen production, but little has been known for the two florigen genes themselves. In this study, pleiotropism of Rice Flowering Locus T 1 (RFT1), one of the two florigen genes in rice, was firstly evaluated using near isogenic lines (NILs) carrying RFT1 alleles from the indica rice cultivars Zhenshan 97 (ZS97) and Milyang 46, respectively, and then determined by transformation of the RFT1 ZS97 allele into a japonica rice variety, Zhonghua 11. The RFT1 ZS97 allele was shown to delay heading and increase plant height, grain weight, grain number and grain yield, indicating that RFT1 plays an important role in the growth and development of rice. This study has also validated the potential of using a new type of genetic resource, sequential residual heterozygotes (SeqRHs), for QTL fine-mapping. A step-by-step approach was employed for SeqRHs identification, NIL development and QTL fine-mapping. The heterozygous segments and candidate QTL regions were gradually narrowed down. Eventually, the QTL region was delimited to a 1.7 kb region containing a single gene.

An observation on the long-term efficacy of recombinant hepatitis B vaccines among the newborns / 预防医学

Objective evaluate the long-term efficacy of the recombinant hepatitis B vaccines (HBV) among the newbornswith vaccination at birth. Methods During 1996-1997, 135 newborns were selected from Deqing according to the inclusioncriterion. They were divided into 2 groups: a group of 35 newborns whose mother was HBsAg positive) and a group of 100newbornswhose mother was HBsAg negative. All 135 newborns routinely received 3 doses of yeast -derived hepatitis Bvaccines (i.e. the first dose at birth, the second dose at 1 month old, and the third dose at 6 months old) . Serologicalmarkers to HBV were repeatedly assessed at 3 follow-up stages (i.e. the first follow-up at 12 months, the second follow-upat 2010, the third follow-up at 2012) . Results Participants remained in the study at 3 follow-upstages were 123(91.11%), 95(70.37%) and 46(34.07%) respectively. Participants' serum HBsAg were negative at all 3 follow-upstages. Among participants whose mothers were HBsAg positive, 3 participants were found to be HBcAb positive in 2010,and no new HBcAb positive participants were found in 2012. The rates of HBsAb positive at 3 follow-up stages were 88.89%, 81.48%, and 80.00% respectively. The HBsAb geometric mean concentrations (GMCs) of participants at their 12 monthsold were significantly positively associated with those in 2010 and those in 2012(P<0.05) . Among participants whosemothers were HBsAg negative, no HBcAb positive participants were found. The rates of HBsAb positive at 3 follow-up stageswere 91.18%, 54.41%, and 52.78% respectively. No correlation was found among HBsAb GMCs of participants at 12 monthsold, in 2010 and in 2012. No correlation was found between boost vaccination and the rate of HBsAg positive, afteradjustment of the HBsAg status of their mothers. Conclusion The efficacy of the yeast-derived HBV could sustain for at least13-15 years, and the general population do not need booster immunization. After the 3-dose immunization, the HBsAblevels of the healthy mothers' 12-months-old children were related to those of their adolescence.

Detection of QTLs for Yield Heterosis in Rice Using a RIL Population and Its Testcross Population.

Analysis of the genetic basis of yield heterosis in rice was conducted by quantitative trait locus mapping using a set of 204 recombinant inbred lines (RILs), its testcross population, and mid-parent heterosis dataset (HMP). A total of 39 QTLs for six yield traits were detected, of which three were detected in all the datasets, ten were common to the RIL and testcross populations, six were common to the testcross and HMP, and 17, 2, and 1 were detected for RILs, testcrosses, and HMP, respectively. When a QTL was detected in both the RIL and testcross populations, the difference between TQ and IR24 and that between Zh9A/TQ and Zh9A/IR24 were always in the same direction, providing the potential to increase the yield of hybrids by increasing the yield of parental lines. Genetic action mode of the 39 QTLs was inferred by comparing their performances in RILs, testcrosses, and HMP. The genetic modes were additive for 17 QTLs, dominance for 12 QTLs, and overdominance for 10 QTLs. These results suggest that dominance and overdominance are the most important contributor to yield heterosis in rice, in which the accumulative effects of yield components play an important role.

Fine mapping of qHd1, a minor heading date QTL with pleiotropism for yield traits in rice (Oryza sativa L.).

KEY MESSAGE: A minor QTL for heading date located on the long arm of rice chromosome 1 was delimitated to a 95.0-kb region using near isogenic lines with sequential segregating regions. Heading date and grain yield are two key factors determining the commercial potential of a rice variety. In this study, rice populations with sequential segregating regions were developed and used for mapping a minor QTL for heading date, qHd1. A total of 18 populations in six advanced generations through BC2F6 to BC2F11 were derived from a single BC2F3 plant of the indica rice cross Zhenshan 97 (ZS97)///ZS97//ZS97/Milyang 46. The QTL was delimitated to a 95.0-kb region flanked by RM12102 and RM12108 in the terminal region of the long arm of chromosome 1. Results also showed that qHd1 was not involved in the photoperiodic response, having an additive effect ranging from 2.4 d to 2.9 d observed in near isogenic lines grown in the paddy field and under the controlled conditions of either short day or long day. The QTL had pleiotropic effects on yield traits, with the ZS97 allele delaying heading and increasing the number of spikelets per panicle, the number of grains per panicle and grain yield per plant. The candidate region contains ten annotated genes including two genes with functional information related to the control of heading date. These results lay a foundation for the cloning of qHd1. In addition, this kind of minor QTLs could be of great significance in rice breeding for allowing minor adjustment of heading date and yield traits.

The long-term efficacy of recombinant hepatitis B vaccines for children / 预防医学

Objective To observe long-term efficacy of recombinant hepatitis B vaccines for children received fundamental immunization or booster dose. Methods 493 school students from Deqing county with complete information of immunization history were investigated and their serological markers were detected. 430 students received booster dose vaccines at 3-11 years old and were defined as booster group while the remaining 63 students were defined as fundamental group. Results All vaccines the 493 students received for fundamental immunization were recombinant. Compared with fundamental group(57. 14%),booster group had significantly higher Anti-HBs positive rate of 91. 40%(P<0. 01). And the Anti-HBs positive rate had a high level of 94. 99% when 0-5 years after booster immunization while it declined to 64. 71% after 8-15 years and showed no significant difference compared with fundamental group. Conclusion Anti-HBs level and anti -HBs positive rate can significantly increase for short periods after booster immunization,and may decline considerably for long-term. Immunologic amnesia rate is low when 3 -11 years after fundamental immunization among infants.

Prevalence of occult hepatitis B virus infection and its phylogenetic features among mother-teenager pairs / 中华流行病学杂志

Objective Prevalence of occult hepatitis B virus (HBV) infection (OBI) was investigated in a paired mother-teenager population and HBV S gene variation including overt and occult HBV,was determined.Methods A follow-up study based on an initial survey of 135 mother-teenager pairs was carried out through collection of questionnaires and blood samples HBsAg were detected by ELISA method,viral load by PCR amplification and HBV S gene by phylogenetic analysis.Results 102 pairs of subjects were followed-up.Blood samples from 94 mothers and 101children were collected.OBI prevalence in mothers was 10.0％ (6/60),significantly higher than 2.0％(2/101) in teenagers.Medians of viral load were 399.9 IU/ml and 247.6 IU/ml in overt and occult HBV strains,but without significant difference.1 occult HBV strain belonged to genotype B with serotype adw while the other 7 were genotype C with serotype adr.15 of the overt HBV strains belonged to genotype B with serotype adw and the other 8 were genotype C with serotype adr.Proportions of genotype-C strains were significantly higher in occult HBV strains than in overt HBV strains.Conclusion OBI was seen in teenage-mother population.