Epidemiological behaviour and interventions of malaria in Niger, 2010-2019: a time-series analysis of national surveillance data.

BACKGROUND: Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. METHODS: A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. RESULTS: Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10-24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. CONCLUSIONS: The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

Nonlinear phase error correction method based on multi-grayscale coding.

Fringe projection profilometry is a non-contact and highly efficient 3D measurement technique widely used in various applications. However, the nonlinear intensity response of digital projectors affects measurement accuracy. While increasing the number of fringe projections can reduce the errors caused by nonlinear problems, it significantly prolongs the measurement time. In order to improve both accuracy and speed simultaneously, a nonlinear phase error correction method based on multi-grayscale coding is proposed. The intensity response curve of the system is fitted by the grayscale images, and then the grayscale values of the phase-shifting fringe images are corrected to reduce the nonlinear error. In order to reduce the number of fringe projections and speed up the measurement, the multi-grayscale coding method is used to divide the phase interval by the order of the gray values of the same pixel in multiple grayscale images. The experimental results validate the efficacy of the proposed multi-grayscale coding method. An accurate phase calculation is achieved, and a single reconstruction can be achieved with only seven photos. After the nonlinear correction, the phase accuracy of the three-step phase-shifting algorithm is increased by 50.77%, and the reconstruction accuracy of the standard ball is increased by 46.38%.

Crystal structure of the plant feruloyl-coenzyme A monolignol transferase provides insights into the formation of monolignol ferulate conjugates.

Lignin is a highly complex phenolic polymer which is essential for plants, but also makes it difficult for industrial processing. Engineering lignin by introducing relatively labile linkages into the lignin backbone can render it more amenable to chemical depolymerization. It has been reported that introducing a feruloyl-coenzyme A monolignol transferase from Angelica sinensis (AsFMT) into poplar could incorporate monolignol ferulate conjugates (ML-FAs) into lignin polymers, suggesting a promising way to manipulate plants for readily deconstructing. FMT catalyzes a reaction between monolignols and feruloyl-CoA to produce ML-FAs and free CoA-SH. However, the mechanisms of substrate specificity and catalytic process of FMT remains poorly understood. Here we report the structure of AsFMT, which adopts a typical fold of BAHD acyltransferase family. Structural comparisons with other BAHD homologs reveal several unique structural features of AsFMT, different from those of the BAHD homologs. Further molecular docking studies showed that T375 in AsFMT may function as an oxyanion hole to stabilize the reaction intermediate and also proposed a role of H278 in the binding of the nucleophilic hydroxyl group of monolignols. Together, this study provides important structural insights into the reactions catalyzed by AsFMT and will shed light on its future application in lignin engineering.

Profile and dynamics of infectious diseases: a population-based observational study using multi-source big data.

BACKGROUND: The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. METHODS: In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. RESULTS: In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P < 0.0001). Urban areas had a significantly higher ID than rural areas, with a relative risk of 1.25 (95% CI 1.23-1.27). Adolescents aged 10-19 years had the highest ID of varicella, women aged 20-39 years had significantly higher IDs of syphilis and trichomoniasis, and people aged ≥ 60 years had significantly higher IDs of zoster and viral conjunctivitis (all P < 0.05). CONCLUSIONS: Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.

Identification and characterization of unique 5-hydroxyisoflavonoid biosynthetic key enzyme genes in Lupinus albus.

KEY MESSAGE: 5-Hydroxyisoflavonoids, no 5-deoxyisoflavonoids, in Lupinus species, are due to lack of CHRs and Type II CHIs, and the key enzymes of isoflavonoid biosynthetic pathway in white lupin were identified. White lupin (Lupinus albus) is used as food ingredients owing to rich protein, low starch, and rich bioactive compounds such as isoflavonoids. The isoflavonoids biosynthetic pathway in white lupin still remains unclear. In this study, only 5-hydroxyisoflavonoids, but no 5-deoxyisoflavonoids, were detected in white lupin and other Lupinus species. No 5-deoxyisoflavonoids in Lupinus species are due to lack of CHRs and Type II CHIs. We further found that the CHI gene cluster containing both Type I and Type II CHIs possibly arose after the divergence of Lupinus with other legume clade. LaCHI1 and LaCHI2 identified from white lupin metabolized naringenin chalcone to naringenin in yeast and tobacco (Nicotiana benthamiana), and were bona fide Type I CHIs. We further identified two isoflavone synthases (LaIFS1 and LaIFS2), catalyzing flavanone naringenin into isoflavone genistein and also catalyzing liquiritigenin into daidzein in yeast and tobacco. In addition, LaG6DT1 and LaG6DT2 prenylated genistein at the C-6 position into wighteone. Two glucosyltransferases LaUGT1 and LaUGT2 metabolized genistein and wighteone into its 7-O-glucosides. Taken together, our study not only revealed that exclusive 5-hydroxyisoflavonoids do exist in Lupinus species, but also identified key enzymes in the isoflavonoid biosynthetic pathway in white lupin.

MYB20, MYB42, MYB43, and MYB85 Regulate Phenylalanine and Lignin Biosynthesis during Secondary Cell Wall Formation.

Lignin is a phenylpropanoid-derived polymer that functions as a major component of cell walls in plant vascular tissues. Biosynthesis of the aromatic amino acid Phe provides precursors for many secondary metabolites, including lignins and flavonoids. Here, we discovered that MYB transcription factors MYB20, MYB42, MYB43, and MYB85 are transcriptional regulators that directly activate lignin biosynthesis genes and Phe biosynthesis genes during secondary wall formation in Arabidopsis (Arabidopsis thaliana). Disruption of MYB20, MYB42, MYB43, and MYB85 resulted in growth development defects and substantial reductions in lignin biosynthesis. In addition, our data showed that these MYB proteins directly activated transcriptional repressors that specifically inhibit flavonoid biosynthesis, which competes with lignin biosynthesis for Phe precursors. Together, our results provide important insights into the molecular framework for the lignin biosynthesis pathway.

Population aging and trends of pulmonary tuberculosis incidence in the elderly.

BACKGROUND: To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly. METHODS: We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (< 60 years) through logistic model and Join-point regression model. RESULTS: Among the total PTB cases, 77,192(32.2%) were elderly. Compared with non-elderly patients, newly active elderly PTB patients account for a greater proportion of male cases (OR 1.688, 95% CI 1.656-1.722), rural population cases (OR 3.411, 95% CI 3.320-3.505) and bacteriologically confirmed PTB cases (OR 1.213, 95%CI 1.193-1.234). The annual reported incidence of total, elderly, pulmonary bacteriologically confirmed cases were 35.21, 68.84, 35.63 (per 100,000), respectively. The annual reported incidence of PTB in the whole population, the elderly group and the non-elderly group has shown a slow downward trend since 2008. The joinpoint regression model showed that the overall reported incidence of PTB in the elderly significantly decreased from 2007 to 2017 (APC = -5.3, P < 0.05). The reported incidence of bacteriologically confirmed PTB among elderly patients declined rapidly from 2005 to 2014(2005-2010 APC = -7.2%, P < 0.05; 2010-2014 APC = -22.6%, P < 0.05; 2014-2017 APC = -9.0%, P = 0.1). The reported incidence of clinically diagnosed PTB among elderly patients from 2005 to 2017 (11.48-38.42/100,000) increased by about 235%. It rose significantly from 2007 to 2014 (APC = 9.4, P<0.05). CONCLUSIONS: Compared with the non-elderly population, the reported incidence of PTB in the elderly population is higher. The main burden of PTB will shift to the elderly, men, rural population, and clinically diagnosed patients. With the intensification of aging, more researches on elderly PTB prevention and treatment will facilitate the realization of the global tuberculosis (TB) control targets.

Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

Ambient air pollutants, diabetes and risk of newly diagnosed drug-resistant tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far. METHODS: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied. RESULTS: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance. CONCLUSIONS: O3 contributed to an elevated risk of TB resistance but PM2.5, PM10, SO2, NO2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.

Distributions of arsenic and other heavy metals, and health risk assessments for groundwater in the Guanzhong Plain region of China.

The aim of this study was to evaluate the quality of shallow groundwater and deep groundwater in the Guanzhong Plain region of China, as well as the related health risk to humans. In total, 130 groundwater samples were collected comprising 116 from shallow groundwater (dug wells) and 14 from deep groundwater (drilled wells). The water samples were analyzed to determine the levels of As and 12 other heavy metals (Al, Cd, Mn, Cr, V, Fe, Ni, Cu, Zn, Co, Pb, and Mo). The results showed that the concentrations of As and other heavy metals in the deep groundwater samples were lower than the safe limits, but the Cr concentrations in some shallow groundwater samples exceeded the safe limits. The heavy metal pollution index and heavy metal evaluation index both showed that As and other heavy metals were pollutants at low levels in all of the shallow and deep groundwater sample. Health risk assessments showed that the deep groundwater samples had no associated non-carcinogenic health risks, whereas the shallow groundwater samples had non-carcinogenic health risks due to contamination with Cr and As. Some shallow groundwater samples had associated carcinogenic health risks due to contamination with Cr and As, whereas the deep groundwater samples only had carcinogenic health risks because of contamination with Cr. These results suggest that local residents and government departments should be made aware of Cr and As pollution in shallow groundwater.

Association between economic development level and tuberculosis registered incidence in Shandong, China.

BACKGROUND: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. METHODS: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention. RESULTS: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. CONCLUSION: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018.

BACKGROUND: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018. METHODS: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out. RESULTS: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model. CONCLUSION: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.

Epidemiological characteristics of pulmonary tuberculosis among children in Shandong, China, 2005-2017.

BACKGROUND: Diagnosis of tuberculosis (TB) in children is challenging. Epidemiological data of childhood pulmonary tuberculosis (PTB) are urgently needed. METHODS: We described trends in epidemiology, clinical characteristics, and treatment outcomes in seven cities of Shandong province, China, during 2005-2017. Data were collected from the China Information System for Disease Control and Prevention. RESULTS: Among 6283 (2.4% of all PTB) PTB cases aged < 18 years, 56.5% were male patients, 39.3% were smear-positive and 98.6% were new cases. The overall incidence of childhood PTB declined (7.62 to 3.74 per 100,000) during 2005-2017, with a non-significant change of annual percentage after 2010. While the incidence of smear-positive PTB (6.09 to 0.38 per 100,000 population) decreased significantly, but the incidence of smear-negative PTB (1.52 to 3.36 per 100,000 population) increased significantly during 2005-2017. The overall treatment success occurred among 94.2% childhood PTB. Ten children (0.2%) died. CONCLUSION: The overall incidence of childhood PTB declined significantly with the disease burden shifting from smear-positive PTB to smear-negative PTB. The discrepancies between notifications and estimations in both TB morbidity and mortality of children need to be addressed urgently.

[Unconstrained detection of ballistocardiogram and heart rate based on vibration acceleration].

The requirement for unconstrained monitoring of heartbeat during sleep is increasing, but the current detection devices can not meet the requirements of convenience and accuracy. This study designed an unconstrained ballistocardiogram (BCG) detection system using acceleration sensor and developed a heart rate extraction algorithm. BCG is a directional signal which is stronger and less affected by respiratory movements along spine direction than in other directions. In order to measure the BCG signal along spine direction during sleep, a 3-axis acceleration sensor was fixed on the bed to collect the vibration signals caused by heartbeat. An approximate frequency range was firstly assumed by frequency analysis to the BCG signals and segmental filtering was conducted to the original vibration signals within the frequency range. Secondly, to identify the true BCG waveform, the accurate frequency band was obtained by comparison with the theoretical waveform. The J waves were detected by BCG energy waveform and an adaptive threshold method was proposed to extract heart rates by using the information of both amplitude and period. The accuracy and robustness of the BCG detection system proposed and the algorithm developed in this study were confirmed by comparison with electrocardiogram (ECG). The test results of 30 subjects showed a high average accuracy of 99.21% to demonstrate the feasibility of the unconstrained BCG detection method based on vibration acceleration.

Cellular and Molecular Analysis of Dendritic Morphogenesis in a Retinal Cell Type That Senses Color Contrast and Ventral Motion.

As neuronal dendrites develop, they acquire cell-type-specific features including characteristic size, shape, arborization, location and synaptic patterns. These features, in turn, are major determinants of type-specific neuronal function. Because neuronal diversity complicates the task of relating developmental programs to adult structure and function, we analyzed dendritic morphogenesis in a single retinal ganglion cell (RGC) type in mouse called J-RGC. We documented the emergence of five dendritic features that underlie J-RGC physiology: (1) dendritic field size, which approximate receptive field size; (2) dendritic complexity, which affects how J-RGCs sample space; (3) asymmetry, which contributes to direction-selectivity; (4) restricted lamination within the inner plexiform layer (IPL), which renders J-RGCs responsive to light decrements; and (5) distribution of synaptic inputs, which generate a color-opponent receptive field. We found dendritic growth in J-RGCs is accompanied by a refinement in dendritic self-crossing. Asymmetry arises by a combination of selective pruning and elaboration, whereas laminar restriction results from biased outgrowth toward the outermost IPL. Interestingly, asymmetry develops in a protracted dorsoventral wave, whereas lamination does so in a rapid centrifugal wave. As arbors mature, they acquire excitatory and inhibitory synapses, with the latter forming first and being concentrated in proximal dendrites. Thus, distinct mechanisms operate in different spatiotemporal dimensions of J-RGC dendritic patterning to generate the substrate for specific patterns of synaptogenesis. Finally, we asked whether the defining molecular signature of J-RGCs, the adhesion molecule JAM-B, regulates morphogenesis, and showed that it promotes dendro-dendritic interactions. Our results reveal multiple mechanisms that shape a dendritic arbor.SIGNIFICANCE STATEMENT Visual perception begins in the retina, where distinct types of retinal ganglion cells (RGCs) are tuned to specific visual features such as direction of motion. The features to which each RGC type responds are determined largely by the number and type of synaptic inputs it receives, and these, in turn, are greatly influenced by the size, shape, arborization pattern, and location of its dendrites. We analyzed dendritic morphogenesis in a functionally characterized RGC type, the J-RGC, demonstrating distinct mechanisms that operate in different dimensions to generate the dendritic scaffold and synaptic patterns for feature detection. Our work elucidates cellular and molecular mechanisms that shape dendritic arbors and synaptic distribution, enabling J-RGC connectivity and thus, function.

Genistein-Specific G6DT Gene for the Inducible Production of Wighteone in Lotus japonicus.

Prenylated isoflavonoids have been found in several legume plants, and they possess various biological activities that play important roles in both plant defense and human health. However, it is still unknown whether prenylated isoflavonoids are present in the model legume plant Lotus japonicus. In the present study, we found that the prenylated isoflavonoid wighteone was produced in L. japonicus when leaf was supplemented with genistein. Furthermore, a novel prenyltransferase gene, LjG6DT, was identified, which shared high similarity with and was closely related to several known prenyltransferase genes involved in isoflavonoid biosynthesis. The recombinant LjG6DT protein expressed in yeast exhibited prenylation activity toward genistein as an exclusive substrate, which produced wighteone, a prenylated genistein at the C-6 position that occurs normally in legume plants. The LjG6DT-green fluorescent protein (GFP) fusion protein is targeted to plastids. The transcript level of LjG6DT is induced by glutathione, methyl jasmonate and salicylic acid, implying that LjG6DT is involved in stress response. Overexpression of LjG6DT in L. japonicus hairy roots led to increased accumulation of wighteone when genistein was supplied, indicating that LjG6DT is functional in vivo. Feeding assays with the upstream intermediate naringenin revealed that accumulation of wighteone in L. japonicus was dependent on genistein supplementation, and accumulation of wighteone is competed by genistein methylation. This study demonstrated that phytoalexin wighteone is inducibly produced in L. japonicus, and it provides new insight into the biosynthesis and accumulation of prenylated isoflavonoids in legume plants.

The impact of outdoor air pollutants on outpatient visits for respiratory diseases during 2012-2016 in Jinan, China.

BACKGROUND: Few studies have investigated the associations between outdoor air pollution and outpatient visits for respiratory diseases (RDs) in general population. METHODS: We collected daily outpatient data of primary RDs from five hospitals in Jinan during January 2012 and December 2016, as well as daily measurements of air pollutants from the Jinan Environmental Monitoring Center and daily meteorological variables from the China Meteorological Data Sharing Service System. A generalized additive model (GAM) with quasi-Poisson regression was constructed to estimate the associations between daily average concentrations of outdoor air pollutants (PM2.5,PM10, SO2, NO2, CO and O3) and daily outpatient visits of RDs after adjusting for long-time trends, seasonality, the "day of the week" effect, and weather conditions. Subgroup analysis stratified by gender, age group and the type of RDs was conducted. RESULTS: A total of 1,373,658 outpatient visits for RDs were identified. Increases of 10 µg/m3 in PM2.5, PM10, NO2, CO and O3 were associated with0.168% (95% CI, 0.072-0.265%), 0.149% (95% CI, 0.082-0.215%), 0.527% (95% CI, 0.211-0.843%), 0.013% (95% CI, 0.003-0.023%), and 0.189% (95% CI, 0.032-0.347%) increases in daily outpatient visits for RDs, respectively. PM2.5 and PM10 showed instant and continuous effects, while NO2, CO and O3 showed delayed effects on outpatient visits for RDs. In stratification analysis, PM2.5 and PM10 were associated with acute RDs only. CONCLUSIONS: Exposure to outdoor air pollutants including PM2.5, PM10, NO2, CO and O3 associated with increased risk of outpatient visits for RDs.

GmMYB58 and GmMYB205 are seed-specific activators for isoflavonoid biosynthesis in Glycine max.

KEY MESSAGE: GmMYB58 and GmMYB205 are key positive regulators that are involved in isoflavonoid biosynthesis in seeds of Glycine max, and they activate the expression of several structural genes in the isoflavonoid pathway. MYB transcription factors (TFs) are major regulators involved in flavonoid/isoflavonoid biosynthesis in many plant species. However, functions of most MYB TFs remain unknown in flavonoid/isoflavonoid pathway in Glycine max. In this study, we identified 321 MYB TFs by genome-wide searching, and further isolated and functionally characterized two MYB TFs, GmMYB58 and GmMYB205. The deduced GmMYB58 and GmMYB205 proteins contain highly conserved R2R3 repeat domain at the N-terminal region that is the signature motif of R2R3-type MYB TFs. GmMYB58 and GmMYB205 were highly expressed in early seed development stages than in the other tested organs. GmMYB58 and GmMYB205 GFP fusion proteins were found to be localized in the nucleus when they were transiently expressed in Arabidopsis thaliana mesophyll protoplast. Both GmMYB58 and GmMYB205 can activate the promoter activities of GmCHS, GmIFS2, and GmHID in the transient trans-activation assays, and the activation of GmHID by both GmMYB58 and GmMYB205 was further confirmed by yeast one-hybrid assay. In addition, over-expression of GmMYB58 and GmMYB205 resulted in significant increases in expression levels of several pathway genes in soybean hairy roots, in particular, IFS2 by more than fivefolds in GmMYB205-over-expressing lines. Moreover, isoflavonoid contents were remarkably enhanced in the GmMYB58 and GmMYB205 over-expressing hairy roots than in the control. Our results suggest that GmMYB58 and GmMYB205 are seed-specific TFs, and they can enhance isoflavonoid biosynthesis mainly through the regulation of GmIFS2 and GmHID in G. max.

Role of a chalcone isomerase-like protein in flavonoid biosynthesis in Arabidopsis thaliana.

Flavonoids are important natural products for plant defence and human health. Although almost all the flavonoid pathway genes have been well-documented by biochemical and/or genetic approaches, the role of the Arabidopsis chalcone isomerase-like (CHIL) gene remains unclear. Two chil mutants with a seed colour similar to that of wild-type Arabidopsis have been identified here, but in sharp contrast to the characteristic transparent testa seed phenotype associated with other known flavonoid pathway genes. CHIL loss-of-function mutations led to a strong reduction in the proanthocyanidin and flavonol levels in seeds, but not in the anthocyanin levels in leaves. CHIL over-expression could partially recover the mutant phenotype of the chil mutant and increased both proanthocyanidin and flavonol accumulation in wild-type Arabidopsis. However, the CHIL gene could not rescue the mutant phenotype of TT5 that encodes the intrinsic chalcone isomerase in Arabidopsis. Parallel phenotypical and metabolic analyses of the chil, tt5, chs, and f3h mutants revealed that, genetically, CHIL functions at the same step as TT5. Moreover, it is demonstrated that CHIL co-expresses, co-localizes, and interacts with TT5 in Arabidopsis for flavonoid production. Based on these genetic and metabolic studies, it is concluded that CHIL functions with TT5 to promote flavonoid production, which is a unique enhancer in the flavonoid pathway.