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Technologies based on digital microfluidics (DMF) have made significant advancements in the automated manipulation of microscale liquids and complex multistep processes. Due to their numerous benefits, such as automation, speed, cost-effectiveness, and minimal sample volume requirements, these systems are particularly well suited for immunoassays. In this review, an overview is provided of diverse DMF manipulation platforms and their applications in immunological analysis. Initially, droplet-driven DMF platforms based on electrowetting on dielectric (EWOD), magnetic manipulation, surface acoustic wave (SAW), and other related technologies are briefly introduced. The preparation of DMF is then described, including material selection, fabrication techniques and droplet generation. Subsequently, a comprehensive account of advancements in the integration of DMF with various immunoassay techniques is offered, encompassing colorimetric, direct chemiluminescence, enzymatic chemiluminescence, electrosensory, and other immunoassays. Ultimately, the potential challenges and future perspectives in this burgeoning field are delved into. [ABSTRACT FROM AUTHOR]

The serotonin 2C receptor (5-HT2CR)-melanocortin pathway plays well-established roles in the regulation of feeding behavior and body weight homeostasis. Dysfunctions in this system, such as loss-of-function mutations in the Htr2c gene, can lead to hyperphagia and obesity. In this study, we aimed to investigate the potential therapeutic strategies for ameliorating hyperphagia, hyperglycemia, and obesity associated with a loss-of-function mutation in the Htr2c gene (Htr2c F327L/Y). We demonstrated that reexpressing functional 5-HT2CR solely in hypothalamic pro-opiomelanocortin (POMC) neurons is sufficient to reduce food intake and body weight in Htr2c F327L/Y mice subjected to a high-fat diet (HFD). In addition, 5-HT2CR expression restores the responsiveness of POMC neurons to lorcaserin, a selective agonist for 5-HT2CR. Similarly, administration of melanotan II, an agonist of the melanocortin receptor 4 (MC4R), effectively suppresses feeding and weight gain in Htr2c F327L/Y mice. Strikingly, promoting wheel-running activity in Htr2c F327L/Y mice results in a decrease in HFD consumption and improved glucose homeostasis. Together, our findings underscore the crucial role of the melanocortin system in alleviating hyperphagia and obesity related to dysfunctions of the 5-HT2CR, and further suggest that MC4R agonists and lifestyle interventions might hold promise in counteracting hyperphagia, hyperglycemia, and obesity in individuals carrying rare variants of the Htr2c gene. [ABSTRACT FROM AUTHOR]

The manipulation of droplets plays a vital role in biomedicine, chemistry, and hydromechanics, especially in microfluidics. Magnetic droplet manipulation has emerged as a prominent and advanced technique in comparison to other modes such as dielectric infiltration, optical radiation, and surface acoustic waves. Its notable progress is attributed to several advantages, including excellent biocompatibility, remote and non-contact control, and instantaneous response. This review provides a comprehensive overview of recent developments in magnetic droplet manipulation and its applications within the biomedical field. Firstly, the discussion involves an examination of the distinctive features associated with droplet manipulation based on both permanent magnet and electromagnet principles, along with a thorough exploration of the influencing factors impacting magnetic droplet manipulation. Additionally, an in-depth review of magnetic actuation mechanisms and various droplet manipulation methods is presented. Furthermore, the article elucidates the biomedical applications of magnetic droplet manipulation, particularly its role in diagnostic assays, drug discovery, and cell culture. Finally, the highlights and challenges of magnetic droplet manipulation in biomedical applications are described in detail. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. Methods: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. Results: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P <.05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P <.05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P >.05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P <.05), but PSD did not increase further (P >.05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:.880,.846, and.821, respectively). Conclusions: Non‐invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF. [ABSTRACT FROM AUTHOR]

Aim. To evaluate volume and strain of the left atrium (LA) in people suffering from paroxysmal atrial fibrillation which is not valvular (NVPAF) using the new technology of left atrial automatic myocardial function imaging (AFILA) and to analyze prognostic factors in patients with NVPAF by follow-up. Methods. Between August 2019 and August 2022, a total of 80 NVPAF patients and 60 normal control patients who were hospitalized in the Department of Cardiology were included in the study. The LA volume and strain parameters of the two groups were analyzed. The differences in LA function (LAF) parameters were compared between the two groups to generate the receiver operating characteristic curve (ROC) and calculate the area under the curve (AUC), sensitivity, and specificity of each parameter. Follow-up was conducted on the 80 NVPAF patients included, their treatment methods after admission and their rehospitalization due to heart events were recorded, and independent risk factors influencing the prognosis of NVPAF were obtained. Results. A total of 140 patients participated in the study, including 80 in the NVPAF group and 60 in the normal control group. There was no statistically significant difference in age and sex between the two groups. Compared to the normal group, the LA minimum volume (LAVmin), LA maximum volume (LAVmax), and volume at onset of LA contraction (LAVpreA) in the NVPAF group were significantly increased. The LA emptying fraction (LAEF) was significantly decreased, and LA reservoir strain (S_R), LA conduit strain (S_CD), and LA contractile strain (S_CT) were significantly compromised (P < 0.05). There was no significant difference in LA evacuation volume (LAEV) reduction (P > 0.05). Logistic regression analysis of LAF parameters in NVPAF patients showed that LAEF and S_R were independently correlated with NVPAF (odds ratio values: 0.883 (0.827–0.943), P < 0.001; 0.916 (0.569–1.474), P = 0.047). The ROC curve results showed that LAEF had a high efficiency in the diagnosis of NVPAF, with P < 0.001, AUC of 0.843, sensitivity of 0.788, and specificity of 0.867. For the LA strain parameters, the S_R test efficiency was higher, with P < 0.001, AUC of 0.762, sensitivity of 0.713, and specificity of 0.783. There was a strong correlation between S_R and LAEF in patients with no end event and those with end event. The ROC curve revealed that the S_R was better than LAEF in predicting prognosis of patients with AF (AUC = 0.914, P < 0.0001 vs. AUC = 0.876, P < 0.0001). S_R of 10.5 and LAEF of 21 were the cut-off values for endpoint events in NVPAF patients, with sensitivity of 0.909 and 0.727 and specificity of 0.904 and 0.901, respectively. Conclusions. AFILA ultrasound technology comprehensively evaluated the LA size and function in patients with NVPAF. The LAEF and S_R were independently correlated with NVPAF and can determine the prognosis of patients with NVPAF. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of this study were to evaluate various branching patterns of segmental bronchi in the left superior and lingular lobes and to survey the anatomical diversity and sex-related differences of these branches in a large sample of the study population. Materials and methods: Overall, 10,000 participants (5428 males, and 4572 females, mean age 50 ± 13.5 years [SD] years; age range: 3–91 years) who underwent multi-slice CT (MSCT) scans between September 2019 and December 2021 were retrospectively included. Using the syngo.via post-processing workstation, the data were applied to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree. The reconstructed images were then interpreted to identify and categorize distinct bronchial patterns in the left superior and lingular lobes. Cross-tabulation analysis and the Pearson Chi-square (χ2) test were used to calculate the constituent ratios of bronchial branch types and determine their significance between male and female groups. Results: Our results revealed mainly four distinct types for the left superior lobe (LSL) bronchial tree, i.e., (B1 + 2, B3, 76.13%); (B1 + 2 + 3, 17.32%); (B1 + 3, B2, 5.74%); (B1a + B3, B1b + B2, 0.81%) and two types for the left lingular lobe (LLL) bronchial tree, i.e., (B4, B5, 91.05%); (B4, B5, B*, 8.95%). There were no significant sex-related differences in the proportion of bronchial branches in LLL (P > 0.05). However, sex-related differences were significant in the proportion of bronchial branches in LSL (P < 0.05). Conclusion: The current study has validated the presence of segmental bronchial variations in the left superior and lingular lobes. These findings may have a crucial effect on the diagnosis of symptomatic patients, as well as in carrying out procedures such as lung resections, endotracheal intubation, and bronchoscopies. [ABSTRACT FROM AUTHOR]

Key message: A new genomic prediction method (RHPP) was developed via combining randomized Haseman–Elston regression (RHE-reg), PCR based on genomic information of core population, and preconditioned conjugate gradient (PCG) algorithm. Computational efficiency is becoming a hot issue in the practical application of genomic prediction due to the large number of data generated by the high-throughput genotyping technology. In this study, we developed a fast genomic prediction method RHPP via combining randomized Haseman–Elston regression (RHE-reg), PCR based on genomic information of core population, and preconditioned conjugate gradient (PCG) algorithm. The simulation results demonstrated similar prediction accuracy between RHPP and GBLUP, and significantly higher computational efficiency of the former with the increase of individuals. The results of real datasets of both bread wheat and loblolly pine demonstrated that RHPP had a similar or better predictive accuracy in most cases compared with GBLUP. In the future, RHPP may be an attractive choice for analyzing large-scale and high-dimensional data. [ABSTRACT FROM AUTHOR]

The protein phosphatase 2C (PP2C) constitutes a large gene family that plays crucial roles in regulating stress responses and plant development. A recent study has shown the involvement of an AtPP2C family member in long-distance nitrogen signaling in Arabidopsis. However, it remains unclear whether maize adopts a similar mechanism. In this study, we conducted a genome-wide survey and expression analysis of the PP2C family in maize. We identified 103 ZmPP2C genes distributed across 10 chromosomes, which were further classified into 11 subgroups based on an evolutionary tree. Notably, cis-acting element analysis revealed the presence of abundant hormone and stress-related, as well as nitrogen-related, cis-elements in the promoter regions of ZmPP2Cs. Expression analysis demonstrated the distinct expression patterns of nine genes under two nitrogen treatments. Notably, the expression of ZmPP2C54 and ZmPP2C85 in the roots was found to be regulated by long-distance signals from the shoots. These findings provide valuable insights into understanding the roles of ZmPP2Cs in long-distance nitrogen signaling in maize. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of this study were to evaluate the various branching patterns of segmental bronchi in the right middle lobe (RML) and to survey the anatomical diversity and sex-related differences of these branches in a large sample of the study population. Materials and methods: In this retrospective board-approved study with informed consent, 10,000 participants (5428 males and 4,572 females, mean age 50 ± 13.5 years [SD]; age range: 3–91 years) who underwent multi-slice CT (MSCT) scans from September 2019 to December 2021 were retrospectively included. The data were applied to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree using the syngo.via post-processing workstation. The reconstructed images were then interpreted to locate and classify distinct bronchial patterns in the RML. Cross-tabulation analysis and the Pearson chi-square test were used to calculate the constituent ratios of bronchial branch types and determine their significance between male and female groups. Results: Our results revealed that the segmental bronchial ramifications of the RML were classified into two types mainly, i.e., bifurcation (B4, B5, 91.42%) and trifurcation (B4, B5, B*, 8.58%). There were no significant sex-related differences in the proportion of bronchial branches in the RML (P > 0.05). Conclusion: The current study has confirmed the presence of segmental bronchial variations in the RML lobe using 3D reconstruction and virtual bronchoscopy. These findings may have significant implications for the diagnosis of symptomatic patients and for carrying out specific procedures like bronchoscopy, endotracheal intubation, and lung resection. [ABSTRACT FROM AUTHOR]

Background: Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results: We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion: These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons. [ABSTRACT FROM AUTHOR]

Objective: To review the imaging characteristics and evaluate the diagnostic value of echocardiography for fetal congenitally unguarded tricuspid valve orifice (CUTVO). Methods: Doppler echocardiography was performed and the images were compared with operative and necropsy findings in ten fetuses with CUTVO. The aim of the study was to summarize the characteristics of fetal echocardiography and analyze the causes of missed diagnoses and misdiagnoses. Results: There were six cases with complete absence (60%) and four cases with partial absence of the tricuspid leaflet (40%). Among all cases, six cases were consistent with the ultrasonic diagnosis. CUTVO ultrasonographic characteristics consist of the atrioventricular connection with normal arteries and the tricuspid valve device partially or completely absent. The annulus of the tricuspid valve can be described as "empty" in the apical four‐chamber view, Doppler evaluation shows to‐and‐fro flow across the tricuspid orifice with low velocity and two‐way spectrum. Conclusion: Fetal echocardiography can accurately diagnose CUTVO, but missed diagnosis and misdiagnosis should be reduced. [ABSTRACT FROM AUTHOR]

Inherent hemispheric asymmetry is important for cognition, language and other functions. Describing normal brain and asymmetry development during early development will improve our understanding of how different hemispheres prioritize specific functions, which is currently unknown. Here, we analysed developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. Changes in the patterns of protein expression differed in the bilateral frontal lobes. Our results show that brain asymmetry can be observed in early development. These findings can guide researchers in further investigations of the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics and human brain mapping studies. Proteomic analysis of human early fetal brain tissue is undertaken to investigate bilateral developmental changes of protein expression and left-right asymmetries of protein expression. [ABSTRACT FROM AUTHOR]

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1–5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.A newly identified exercise-induced signalling metabolite—an amidated conjugate of lactate and phenylalanine—can reduce food intake and improve blood glucose homeostasis. [ABSTRACT FROM AUTHOR]

A novel ionic liquid (i.e. 1-butyl-3-methylimidazolium hexafluorophosphate [C4MIM]PF6) doped poly-N-phenylpyrrole (PPPy) composite coating ([C4MIM]PF6@PPPy) was successfully fabricated by direct electrochemical polymerization on the surface of a NiTi substrate as a solid phase microextraction fiber. To obtain a uniform and stable fiber, the NiTi substrate was initially hydrothermally treated in sodium hydroxide solution for the in situ growth of titanium–nickel oxide composite nanoflakes (TiO2–NiOCNFs). After electrochemical deposition, dense [C4MIM]PF6@PPPy composite nanoparticles were coated on the surface of the TiO2–NiOCNF coating and porous nanostructures were obtained. Due to the embedding of an ionic liquid in the PPPy coating, the resulting [C4MIM]PF6@PPPy@TiO2–NiOCNFs@NiTi fiber shows higher extraction selectivity for polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) with aromatic compounds as model analytes. The new fiber was used to extract PCBs and PAHs in water samples, which were quantified by HPLC with UV detection. Moreover the fabricated [C4MIM]PF6@PPPy@TiO2–NiOCNFs@NiTi fiber exhibits the best extraction capability for PCBs and PAHs in the presence of 0.05% (V/V) [C4MIM]PF6. Under the optimized conditions, the calibration curves were linear in the range of 0.05–350 μg L−1 for PCBs and 0.1–350 μg L−1 for PAHs with correlation coefficients (r) above 0.9984. The limits of detection (LODs) and limits of quantitation (LOQs) varied from 0.015 to 0.095 μg L−1 and from 0.049 to 0.316 μg L−1, respectively. Furthermore, the enrichment factors (EFs) ranged from 67 to 237. Relative standard deviations (RSDs) for single fiber repeatability were less than 6.0% and 6.9% for intra-day and inter-day measurements, respectively. The developed SPME-HPLC method was successfully applied to the extraction and detection of trace PCBs and PAHs in different real water samples. Recoveries from 83.0% to 103% were obtained with RSDs below 8.5%. In addition, the novel [C4MIM]PF6@PPPy@TiO2–NiOCNFs@NiTi fiber exhibits high stability and long lifespan. [ABSTRACT FROM AUTHOR]

Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In addition, PNNs in the terete hypothalamic nucleus display a sexual dimorphism with females higher than males, and high-fat diet feeding increases terete PNNs only in female mice but not in male mice. On the other hand, PNNs in other hypothalamic regions are not influenced by sex, gonadal hormones or dietary interventions. In summary, we demonstrated that hypothalamic PNNs are regulated in a region-specific manner and these results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones and diets. [ABSTRACT FROM AUTHOR]

Detecting genetic regions under selection in structured populations is of great importance in ecology, evolutionary biology and breeding programmes. We recently proposed EigenGWAS, an unsupervised genomic scanning approach that is similar to FST but does not require grouping information of the population, for detection of genomic regions under selection. The original EigenGWAS is designed for the random mating population, and here we extend its use to inbred populations. We also show in theory and simulation that eigenvalues, the previous corrector for genetic drift in EigenGWAS, are overcorrected for genetic drift, and the genomic inflation factor is a better option for this adjustment. Applying the updated algorithm, we introduce the new EigenGWAS online platform with highly efficient core implementation. Our online computational tool accepts plink data in a standard binary format that can be easily converted from the original sequencing data, provides the users with graphical results via the R‐Shiny user‐friendly interface. We applied the proposed method and tool to various data sets, and biologically interpretable results as well as caveats that may lead to an unsatisfactory outcome are given. The EigenGWAS online platform is available at www.eigengwas.com, and can be localized and scaled up via R (recommended) or docker. [ABSTRACT FROM AUTHOR]

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson's. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDRCre). We demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre‐dependent tdTomato expression) is highly overlapping with endogenous VDR mRNAs. These VDR‐expressing cells were enriched in multiple brain regions including the cortex, amygdala, caudate putamen, and hypothalamus among others. In the hypothalamus, VDR partially colocalized with vasopressin, oxytocin, estrogen receptor‐α, and β‐endorphin to various degrees. We further functionally validated our model by demonstrating that the endogenous VDR agonist 1,25‐dihydroxyvitamin D activated all tested tdTomato+ neurons in the paraventricular hypothalamus but had no effect on neurons without tdTomato fluorescence. Thus, we have generated a new mouse tool that allows us to visualize VDR‐expressing cells and to characterize their functions. [ABSTRACT FROM AUTHOR]

In this paper, we address the two-dimensional bin-packing (2BP) problem with variable conflict penalties, which incur if conflicting items are loaded into the same bin. Such a problem is observed in applications such as supermarket chains and automobile components transportation. The problem not only focuses on minimisation of number of bins used, but also deals with the conflict penalties at the same time. We propose a heuristic method based on the IMA algorithm and adapt it to solve this problem. A local search procedure is also designed to further improve the solutions. For instances derived from benchmark test data, the computational results indicate that the adapted IMA heuristic algorithm with local search effectively balances the number of bins used and the conflict penalties. The algorithm outperforms several adapted approaches that are well known for the 2BP problems. [ABSTRACT FROM PUBLISHER]

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female mice. Ablation of TPH2 reduces hypothalamic pro-opiomelanocortin (POMC) neuronal activity robustly in males, but only to a modest degree in females. Deprivation of estrogen by ovariectomy (OVX) causes comparable food intake and weight gain in female control and DRN-specific TPH2 knockout mice. Nevertheless, disruption of TPH2 blunts the anorexigenic effects of exogenous estradiol (E2) and abolishes E2-induced activation of POMC neurons in OVX female mice, indicating that TPH2 is indispensable for E2 to activate POMC neurons and to suppress appetite. Together, our study revealed that TPH2 in the DRN contributes to energy balance regulation in a sexually dimorphic manner. [ABSTRACT FROM AUTHOR]

Obesity has become a global health issue, but effective therapies remain very limited. Adaptive thermogenesis promotes weight loss by dissipating energy in the form of heat, thereby representing a promising target to counteract obesity. Notably, the regulation of thermogenesis is tightly orchestrated by complex neuronal networks, especially those in the hypothalamus. Recent evidence highlights the importance of adenosine monophosphate-activated protein kinase (AMPK) within the ventromedial nucleus of the hypothalamus (VMH) in modulating thermogenesis. Various molecules, such as GLP-1, leptin, estradiol, and thyroid hormones, have been reported to act on the VMH to inhibit AMPK, which subsequently increases thermogenesis through the activation of the sympathetic nervous system (SNS). In this review, we summarize the critical role of AMPK within the VMH in the control of energy balance, focusing on its contribution to thermogenesis and the associated mechanisms. [ABSTRACT FROM AUTHOR]

Coix is a grass crop domesticated as early as the Neolithic era. It is still widely cultivated for both highly nutritional food and medicinal use. However, the genetic study and breeding of this crop are hindered by the lack of a sequenced genome. Here, we report de novo sequencing and assembly of the 1619-Mb genome of Coix , and annotation of 75.39% repeats and 39 629 protein-coding genes. Comparative genomics analysis showed that Coix is more closely related to sorghum than maize, but intriguingly only Coix and maize had a recent genome duplication event, which was not detected in sorghum. We further constructed a genetic map and mapped several important traits, especially the strength of hull. Selection of papery hull (thin: easy dehulling) from the stony hull (thick: difficult dehulling) in wild progenitors was a key step in Coix domestication. The papery hull makes seed easier to process and germinate. Anatomic and global transcriptome analysis revealed that the papery hull is a result of inhibition of cell division and wall biogenesis. We also successfully demonstrated that seed hull pressure resistance is controlled by two major quantitative trait loci (QTLs), which are associated with hull thickness and color, respectively. The two QTLs were further fine mapped within intervals of 250 kb and 146 kb, respectively. These resources provide a platform for evolutionary studies and will facilitate molecular breeding of this important crop. This study constructs a high-quality draft map of the 1.6-Gb genome of Coix aquatica and reveals a special recent whole-genome duplication event. A genetic map is developed, and it is found that a key domestication trait, seed hull pressure resistance, is controlled by two quantitative trait loci associated with thickness and color of hull, respectively. [ABSTRACT FROM AUTHOR]

To increase the predictive accuracy of genomic selection, large-scale phenotypic and genomic data is needed, which results in enormous consumption of computational resources, hampering the feasibility of genomic selection in return. In order to address computational limitation, a rapid genomic selection method HEAPY|A is developed in this study, combining Haseman-Elston (HE) model and algorithm for proven and young (APY). The proposed approach utilizes (i) HE regression to estimate the heritability and then (ii) APY to solve the inverse of the large matrix in best linear prediction (BLP); both HE and APY can reduce the computational cost compared with conventional techniques. When the size of a core population is half of that of a large training population, GBLUP|A, HEAPY|A, and HEBLP|A have similar performance in simulation studies (the core population can be further reduced if the training population size is further increased). When the size of a core population is half of that of a small training population, the predictive accuracy of HEAPY|A is a little lower than that of GBLUP|A and HEBLP|A in simulation study and empirical data—an Arabidopsis thaliana F2 population. HEAPY|A helps in predicting large genomic selection dataset with comparable accuracy without significant expense of time seen in traditional genomic selection algorithm. [ABSTRACT FROM AUTHOR]

Brown and beige adipocytes are mainly responsible for nonshivering thermogenesis or heat production, despite the fact that they have distinguished features in distribution, developmental origin, and functional activation. As a nutrient sensor and critical regulator of energy metabolism, mechanistic target of rapamycin (mTOR) also plays an important role in the development and functional maintenance of adipocytes. While the recent studies support the notion that mTOR (mTORC1 and mTORC2) related signaling pathways are of great significance for thermogenesis and the development of brown and beige adipocytes, the exact roles of mTOR in heat production are controversial. The similarities and disparities in terms of thermogenesis might be ascribed to the use of different animal models and experimental systems, distinct features of brown and beige adipocytes, and the complexity of regulatory networks of mTORC1 and mTORC2 in energy metabolism. [ABSTRACT FROM AUTHOR]

miRNAs are important regulators of differentiation, development, and function of brown and beige fat cells. In this study, we identify the role of the miR-199a/214 cluster in the regulation of brown and beige adipocyte development and thermogenesis in vitro and in vivo. We show that expression of the miR-199a/214 cluster is dramatically decreased during brown and beige adipocyte differentiation and in response to cold exposure or β-adrenergic receptor activation. The cluster levels are significantly upregulated in the adipose tissues of obese mice and human subjects. Overexpression of the miR-199a/214 cluster suppresses brown adipocyte differentiation and inhibits thermogenic gene expression and mitochondrial respiration, whereas knockdown of the cluster increases thermogenic gene expression and mitochondrial function in beige adipocytes. In addition, inhibition of the miR-199a/214 cluster promotes beiging effects in vivo. We further show that miR-199a/214 suppresses brown adipocyte differentiation and beige fat development by directly targeting PRDM16 and peroxisome PGC-1α, two key transcriptional regulators of adipose browning. Together, these observations reveal that the miR-199a/214 cluster is a key negative regulator of brown and beige fat development and thermogenesis. [ABSTRACT FROM AUTHOR]

Maize ( Zea mays L.) and Asian rice ( Oryza sativa L.), two most important cereals for human nutrition, have undergone strong artificial selection during a long period of time. Currently, a number of genes with stronger signals of selection have been identified through combining genomic and population genetic approach, but research on artificial selection of maize and Asian rice is scarcely done from the perspective of phenotypic difference of a number of agronomic traits. In this study, such an investigation was carried out on the basis of 179 published studies about phenotypic quantitative trait locus (QTL) mapping of Zea and Oryza species via QTL sign test. At the overall level, the proportions of antagonistic QTLs of Zea and Oryza species were 0.2446 and 0.2382 respectively, deviating significantly from neutrality. It indicated that these two genera have undergone similar selection strength during their evolutionary process. A previous study showed that 4 traits undergoing the directional selection during domestication were identified in Asian rice via QTL sign test, and 16 individual traits in Asian rice and 38 ones in maize that newly detected in this study deviated significantly from neutrality as well, demonstrating the dominant influence of artificial selection on them. Moreover, analysis of different categories of cross type including O. sativa × Oryza rufipogon (perennial and annual forms) crosses, maize × teosinte ( Zea mays subsp. parviglumis) crosses, O. sativa × O. sativa crosses, and maize × maize crosses showed that their proportions of antagonistic QTLs were 0.1869, 0.1467, 0.2649, and 0.2618 respectively. These results revealed that selection strength of domestication is significantly stronger than that of modern genetic improvement. However, interestingly, the proportion of antagonistic QTLs (0.1591) in maize × maize with long-term selection was very similar to that (0.1467) in the maize × teosinte ( Zea mays subsp. parviglumis) crosses. It suggested that some favorable traits could be cultivated within a few decades if we carry out strong selection. In addition, the proportions of antagonistic QTLs of the widely cultivated hybrids of rice (Minghui 63 × Zhenshan 97) and maize (Zheng 58 × Chang 7-2) in China were 0.309 and 0.3472 respectively. It suggested that selection during modern genetic improvement has significantly acted on them. [ABSTRACT FROM AUTHOR]

Key message: We propose a novel computational method for genomic selection that combines identical-by-state (IBS)-based Haseman-Elston (HE) regression and best linear prediction (BLP), called HE-BLP. Abstract: Genomic best linear unbiased prediction (GBLUP) has been widely used in whole-genome prediction for breeding programs. To determine the total genetic variance of a training population, a linear mixed model (LMM) should be solved via restricted maximum likelihood (REML), whose computational complexity is the cube of the sample size. We proposed a novel computational method combining identical-by-state (IBS)-based Haseman-Elston (HE) regression and best linear prediction (BLP), called HE-BLP. With this method, the total genetic variance can be estimated by solving a simple HE linear regression, which has a computational complex of the sample size squared; therefore, it is suitable for large-scale genomic data, except those with which environmental effects need to be estimated simultaneously, because it does not allow for this estimation. In Monte Carlo simulation studies, the estimated heritability based on HE was identical to that based on REML, and the prediction accuracy via HE-BLP and traditional GBLUP was also quite similar when quantitative trait loci (QTLs) were randomly distributed along the genome and their effects followed a normal distribution. In addition, the kernel row number (KRN) trait in a maize IBM population was used to evaluate the performance of the two methods; the results showed similar prediction accuracy of breeding values despite slightly different estimated heritability via HE and REML, probably due to the underlying genetic architecture. HE-BLP can be a future genomic selection method choice for even larger sets of genomic data in certain special cases where environmental effects can be ignored. The software for HE regression and the simulation program is available online in the Genetic Analysis Repository ( GEAR; https://github.com/gc5k/GEAR/wiki). [ABSTRACT FROM AUTHOR]

Gro/Tup1 proteins act as negative transcriptional regulators and play crucial roles in many growth and developmental processes in a wide range of organisms. However, our understanding of Gro/Tup1 protein functions in plants is confined to the model plant Arabidopsis. Here, 11 Gro/Tup1 genes, which were characterized by the typical LisH and WD40 repeat domains, were identified in maize through a genome-wide survey. A phylogenetic analysis revealed that maize Gro/Tup1 proteins could be divided into three subfamilies, in which members shared similar protein and gene structures. The predicted maize Gro/Tup1 genes were distributed on seven chromosomes and segmental duplication contributed to their expansion. Many predicted cis-elements associated with hormones, biotic- or abioticstress responses, meristem and seed development, and circadian rhythms, were found in their putative promoter regions. A potential associated protein analysis identified a large number of candidates, including transcription factors, chromatin-modifying enzymes, protein kinases, and ubiquitinconjugating enzymes. An expression profile derived from the RNA-seq data indicated that Gro/Tup1 genes in maize were widely expressed in various organs and tissues. Quantitative real-time PCR revealed that these genes responded to at least one hormone or abiotic stress, either in roots or in shoots. Our study provides useful information on the Gro/Tup1 genes in maize and will facilitate the further functional validation of these genes in growth and development, hormone responses, and biotic- or abiotic-stress resistance. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is the most important macronutrient for plant growth and development. Hence, understanding genetic architectures and functional genes involved in the response to N deficiency can greatly facilitate the development of low-N-tolerant cultivars. In this study, we collected 212 quantitative trait loci (QTL) of agronomically important traits under low-N stress conditions in maize. We then identified 21 consensus QTL (cQTL) strongly induced for low-N tolerance after excluding overlapping cQTL containing QTL simultaneously identified in meta-analyses of studies performed under other environmental conditions. Among the 21 cQTL, 30 candidate maize genes were identified from maize large-scale differential expression data derived from analyses of low-N stress, and the 12 most important maize orthologs were identified using homologous BLAST analyses of genes with known functions in N use efficiency in model plants. Furthermore, maize orthologs associated with low-N tolerance and metabolism were also predicted using large-scale expression data from other model plants. The present genetic loci and candidate genes indicate the molecular mechanisms of low-N tolerance in maize and may provide information for QTL fine mapping and molecular marker-assisted selection. [ABSTRACT FROM AUTHOR]

To develop genetic markers associated with tolerance to low phosphorus, we identified candidate phosphate starvation responsive ( PSR) genes and developed their intron length polymorphism ( ILP) markers in maize on a genome-wide scale. Based on the known plant PSR genes, 161 candidate PSR genes were identified. Of these genes, 138 genes contained at least one intron and were then used to develop 606 PSR- ILP markers by designing PCR primers to the intron-flanking exonic regions. PCR evaluation was performed on 43 randomly selected PSR- ILP markers in 30 maize inbred lines. Of the primers, 88.4% amplified stable and pure products in all maize inbred lines, and 53.5% of the markers showed ILP, with PIC values ranging from 0.06 to 0.80. The result of clustering analysis of the 30 maize inbred lines, based on the polymorphism of 23 ILP markers, suggests that the ILP markers developed in this study are not only efficient for genetic diversity analysis but also potentially useful for marker assisted selection for tolerance to low phosphorus. [ABSTRACT FROM AUTHOR]

Keywords: genome-wide association study; multi-trait analysis; nested association mapping; pleiotropy; imprinted QTL EN genome-wide association study multi-trait analysis nested association mapping pleiotropy imprinted QTL 1 2 2 08/09/21 20210805 NES 210805 Thanks to the recent advances in genotyping technologies, genome-wide association studies (GWAS) have been an established approach to identifying genetic variants that influence certain characteristics of economic or scientific interest in plants, animals and humans. Multi-trait analysis has been of interest in GWAS due to its potential gain in statistical power and its ability for formal hypothesis testing of biological importance such as pleiotropy vs. linkage. Genome-wide association study, multi-trait analysis, nested association mapping, pleiotropy, imprinted QTL. [Extracted from the article]

The reverse transcription quantitative polymerase chain reaction (RT-qPCR) is a powerful and widely used technique for the measurement of gene expression. Reference genes, which serve as endogenous controls ensure that the results are accurate and reproducible, are vital for data normalization. To bolster the literature on reference gene selection in maize, ten candidate reference genes, including eight traditionally used internal control genes and two potential candidate genes from our microarray datasets, were evaluated for expression level in maize across abiotic stresses (cold, heat, salinity, and PEG), phytohormone treatments (abscisic acid, salicylic acid, jasmonic acid, ethylene, and gibberellins), and different tissue types. Three analytical software packages, geNorm, NormFinder, and Bestkeeper, were used to assess the stability of reference gene expression. The results revealed that elongation factor 1 alpha (EF1α), tubulin beta (β-TUB), cyclophilin (CYP), and eukaryotic initiation factor 4A (EIF4A) were the most reliable reference genes for overall gene expression normalization in maize, while GRP (Glycine-rich RNA-binding protein), GLU1(beta-glucosidase), and UBQ9 (ubiquitin 9) were the least stable and most unsuitable genes. In addition, the suitability of EF1α, β-TUB, and their combination as reference genes was confirmed by validating the expression of WRKY50 in various samples. The current study indicates the appropriate reference genes for the urgent requirement of gene expression normalization in maize across certain abiotic stresses, hormones, and tissue types. [ABSTRACT FROM AUTHOR]

Key message: We develop a set of universal genetic markers based on single-copy orthologous (COSII) genes in Poaceae. Abstract: Being evolutionary conserved, single-copy orthologous (COSII) genes are particularly useful in comparative mapping and phylogenetic investigation among species. In this study, we identified 2,684 COSII genes based on five sequenced Poaceae genomes including rice, maize, sorghum, foxtail millet, and brachypodium, and then developed 1,072 COSII markers whose transferability and polymorphism among five bamboo species were further evaluated with 46 pairs of randomly selected primers. 91.3 % of the 46 primers obtained clear amplification in at least one bamboo species, and 65.2 % of them produced polymorphism in more than one species. We also used 42 of them to construct the phylogeny for the five bamboo species, and it might reflect more precise evolutionary relationship than the one based on the vegetative morphology. The results indicated a promising prospect of applying these markers to the investigation of genetic diversity and the classification of Poaceae. To ease and facilitate access of the information of common interest to readers, a web-based database of the COSII markers is provided (). [ABSTRACT FROM AUTHOR]

As introns are vulnerable to changes such as insertions and deletions when exposed to various evolutionary forces, they constitute a repository for developing genetic markers based on intron length polymorphisms (ILP). This study developed a set of genetic markers that use the potential intron length polymorphism in resistance gene analogs (RGAs) in Zea mays. By searching the genome of Zea mays B73 for the homologs of 73 R genes which have already been identified in plants, we found 861 RGAs, 632 of which have at least one intron that can serve as putative markers targeting the intron length polymorphism in RGAs (RGA-ILP). We developed 1972 candidate markers via electronic PCR (e-PCR) with primer pairs designed in each pair of exonic regions that flank an intron. Furthermore, the performance of RGA-ILP among four maize inbred lines (Huangzao4, B73, Mo17, and Dan340) was evaluated with 69 pairs of randomly selected primers. Of them, 46.4% showed bands that had discriminating length polymorphism, and between any two of the inbred lines the proportion of polymorphism ranged from 23.2 to 31.9%. To make it convenient to use these markers for those interested in molecular breeding of disease-resistant maize, we provide all related information in a web-based database named MaizeRGA, which is available at . [ABSTRACT FROM AUTHOR]

Background: Understanding the history of life requires that we understand the transfer of genetic material across phylogenetic boundaries. Detecting genes that were acquired by means other than vertical descent is a basic step in that process. Detection by discordant phylogenies is computationally expensive and not always definitive. Many have used easily computed compositional features as an alternative procedure. However, different compositional methods produce different predictions, and the effectiveness of any method is not well established. Results: The ability of octamer frequency comparisons to detect genes artificially seeded in cyanobacterial genomes was markedly increased by using as a training set those genes that are highly conserved over all bacteria. Using a subset of octamer frequencies in such tests also increased effectiveness, but this depended on the specific target genome and the source of the contaminating genes. The presence of high frequency octamers and the GC content of the contaminating genes were important considerations. A method comprising best practices from these tests was devised, the Core Gene Similarity (CGS) method, and it performed better than simple octamer frequency analysis, codon bias, or GC contrasts in detecting seeded genes or naturally occurring transposons. From a comparison of predictions with phylogenetic trees, it appears that the effectiveness of the method is confined to horizontal transfer events that have occurred recently in evolutionary time. Conclusions: The CGS method may be an improvement over existing surrogate methods to detect genes of foreign origin. [ABSTRACT FROM AUTHOR]

In higher plants, microRNA (miRNA) is involved in regulation of developmental processes, including sexual organ development. Seven novel miRNA families with one known miRNA were isolated by constructing a small RNA library from a mixture of anther from a cytoplasmic male sterile line and its maintainer. Two miRNAs are conserved in plant species. A total of 18 potential targets were identified for the eight miRNA families, including 15 proteins annotated with function and three unknown proteins. The known proteins include several proteins relevant to cell structure and stress response, transcription factors, and enzymes associated with metabolic and signaling pathways, playing important roles in microspore development. Quantitative real-time PCR assay revealed different expression patterns of the miRNAs between the cytoplasmic male sterile line and its maintainer. Each of the miRNAs tended to be down-regulated after the tetrad stage in a fertile line. However, most of the miRNAs in the cytoplasmic male sterile line were shown to be up-regulated from the tetrad to mononuclear stage, displaying special expression patterns differing from the ones in fertile line. We conclude that additional inactive miRNA pathways are essential during pollen development for a fertile line to ensure male fertility. Contrarily, miRNAs are up-regulated during the period from the tetrad to mononuclear stage, which contributes to pollen abortion for a cytoplasmic male sterile line. [ABSTRACT FROM AUTHOR]

The neuroendocrine system coordinates metabolic and behavioral adaptations to fasting, including reducing energy expenditure, promoting counterregulation, and suppressing satiation and anxiety to engage refeeding. Here, we show that steroid receptor coactivator-2 (SRC-2) in pro-opiomelanocortin (POMC) neurons is a key regulator of all these responses to fasting. POMC-specific deletion of SRC-2 enhances the basal excitability of POMC neurons; mutant mice fail to efficiently suppress energy expenditure during food deprivation. SRC-2 deficiency blunts electric responses of POMC neurons to glucose fluctuations, causing impaired counterregulation. When food becomes available, these mutant mice show insufficient refeeding associated with enhanced satiation and discoordination of anxiety and food-seeking behavior. SRC-2 coactivates Forkhead box protein O1 (FoxO1) to suppress POMC gene expression. POMC-specific deletion of SRC-2 protects mice from weight gain induced by an obesogenic diet feeding and/or FoxO1 overexpression. Collectively, we identify SRC-2 as a key molecule that coordinates multifaceted adaptive responses to food shortage. [Display omitted] • SRC-2 inhibits POMC neurons to suppress energy expenditure during fasting • SRC-2 maintains POMC responses to low glucose to trigger counterregulation • SRC-2 in POMC neurons suppresses satiation and anxiety during refeeding • SRC-2 in POMC neurons mediates diet-induced weight gain Yang et al. demonstrate that SRC-2 in POMC neurons coordinates multifaceted adaptive responses to food shortage, including reducing energy expenditure, promoting counterregulation and suppressing satiation and anxiety to engage refeeding. These effects are mediated by SRC-2 functions to regulate POMC gene expression and modulate POMC neuron activities. [ABSTRACT FROM AUTHOR]

A novel copper-catalyzed oxidation of arene-fused cyclic amines to the corresponding cyclic imides has been developed. The reaction can be used to synthesize 1,3-disubstituted TPD in high yields. [ABSTRACT FROM AUTHOR]

Copper-mediated electrophilic imination of alkenylzirconocenes generated in situ from alkynes and zirconocenes is accomplished under mild reaction conditions. The reaction can be used to prepare various 2-azadienes. [ABSTRACT FROM AUTHOR]

The central nervous system mediates the effects of vitamin D on energy and glucose balance, but the distribution of vitamin D receptor (VDR) in the brain is not clear due to the lack of reliable antibodies. Here, we generated a knock-in VDR-Cre mouse line, in which cre recombinase activity is driven by the endogenous VDR promoter. By mating VDR-Cre mice with TdTomato reporter mice, we found that VDR-expressing neurons are located in multiple brain regions, including the cortex, hypothalamus, amygdala and caudate putamen. We further verified the specificity of our model through single cell RT-PCR, which showed significantly higher vdr expression in tomato+ cells. More importantly, our in vitro electrophysiological study revealed that vitamin D can selectively activate tomato+ neurons, without affecting tomato- neurons. By using immunofluorescence staining, we found a small portion of VDR positive neurons also express oxytocin, ß-endorphin, ERα or serotonin. Interestingly, in the ventromedial hypothalamus, ERα co-localized with only 1% tomato+ neurons in males but 8% tomato+ neurons in females. Taken together, we created and validated a novel VDR-Cre mouse line, which provides a useful tool for future studies to investigate the functions of VDR in the brain. Disclosure: H. Liu: None. [ABSTRACT FROM AUTHOR]

As a body weight management medicine, lorcaserin, a selective agonist of serotonin 2C receptor (5-HT2CR) which is a G protein-coupled receptor, fails to maintain its effect on body weight loss after a long term administration. Thus, it is necessary to find a way to strengthen its effect on obesity treatment. It has been reported that the effect of lorcaserin on body weight loss is by activating Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARH). However, how POMCARH neuron activity changes after long term lorcaserin treatment remains unknown. In the present study, we found that POMCARH neurons cannot maintain its sensitivity to further lorcaserin stimulation after a long term lorcaserin treatment. By using in vitro electrophysiology recording and c-Fos immunostaining in the brain slice from control mice, we found that acute lorcaserin application significantly increased POMCARH neuron activity. However, this activation effect significantly decreased in mice with lorcaserin administration for consecutive 20 days. By in vivo fiber photometry calcium recording, we found that lorcaserin significantly increased POMCARH neuron activity in vivo at first day, but this activation effect decreased after 10 days lorcaserin treatment and almost disappeared after 20 days lorcaserin treatment. We further showed that this desensitization of POMCARH neurons to lorcaserin stimulation is mainly due to a beta-arrestin-mediated excessive internalization of 5-HT2C receptor in POMCARH neurons. Barbadin, a novel selective β-arrestin/adaptor protein 2 interaction inhibitor, maintains POMCARH neuron sensitivity to further lorcaserin stimulation by blocking prolonged lorcaserin-induced aberrant 5-HT2C receptor internalization. Co-treatment with barbadin also prolongs lorcaserin's effect on body weight loss and food intake reduction in mice. Overall, our results may provide a potential strategy for facilitating obesity treatment by lorcaserin. Disclosure: Y. He: None. H. Liu: None. Y. Xu: None. [ABSTRACT FROM AUTHOR]

In the original version of this article the co-corresponding author name is missing. [ABSTRACT FROM AUTHOR]

Phosphorus (P) is required for numerous developmental processes, such as flowering and reproduction, in maize (Zea mays L.). It is also an essential nutrient in fertilizers to sustain high yields in farmlands with insufficient available phosphate, particularly in acid soils in China. Flowering time is a key factor influencing the adaptation of maize to the local environment and is associated with high yields. However, few studies have focused on the genetic characteristics of flowering time under low phosphate conditions. In this study, a recombinant inbred line (RIL) population derived from a cross between X178 and 9782 was evaluated for three flowering time traits under two phosphates (Pi) levels at four locations. We found that low phosphate significantly delayed the flowering stage of maize and proposed the hypothesis of "Phosphorus Accumulation Effect". Mixed-model-based composite interval mapping was used to dissect the genetic basis of the flowering time traits. A total of 41 quantitative trait loci (QTL) was identified for the three flowering time traits through four procedures. Among these 41 QTL, 38 focused on four hot regions, including bin 2.02, bin 2.03, bin 5.04, and bin 6.01. These regions and linked markers should be the targets for fine mapping, map-based cloning, and marker-assisted selection of flowering time and phosphate utilization efficiency. [ABSTRACT FROM AUTHOR]

A correction to the article "Mining for Low-Nitrogen Tolerance Genes by Integrating Meta-Analysis and Large-Scale Gene Expression Data From Maize" by Bowen Luo et al. that was published in a 2015 issue is presented.