The adaptation of bumblebees to extremely high elevation associated with their gut microbiota.

Bumblebees are among the most abundant and important pollinators for sub-alpine and alpine flowering plant species in the Northern Hemisphere, but little is known about their adaptations to high elevations. In this article, we focused on two bumblebee species, Bombus friseanus and Bombus prshewalskyi, and their respective gut microbiota. The two species, distributed through the Hengduan Mountains of southwestern China, show species replacement at different elevations. We performed genome sequencing based on 20 worker bee samples of each species. Applying evolutionary population genetics and metagenomic approaches, we detected genes under selection and analyzed functional pathways between bumblebees and their gut microbes. We found clear genetic differentiation between the two host species and significant differences in their microbiota. Species replacement occurred in both hosts and their bacteria (Snodgrassella) with an increase in elevation. These extremely high-elevation bumblebees show evidence of positive selection related to diverse biological processes. Positively selected genes involved in host immune systems probably contributed to gut microbiota changes, while the butyrate generated by gut microbiota may influence both host energy metabolism and immune systems. This suggests a close association between the genomes of the host species and their microbiomes based on some degree of natural selection.IMPORTANCETwo closely related and dominant bumblebee species, distributed at different elevations through the Hengduan Mountains of southwestern China, showed a clear genomic signature of adaptation to elevation at the molecular level and significant differences in their respective microbiota. Species replacement occurred in both hosts and their bacteria (Snodgrassella) with an increase in elevation. Bumblebees' adaptations to higher elevations are closely associated with their gut microbiota through two biological processes: energy metabolism and immune response. Information allowing us to understand the adaptive mechanisms of species to extreme conditions is implicit if we are to conserve them as their environments change.

Physiological responses and molecular mechanisms of biofilm formation induced by extracellular metabolites of euglena in Pseudomonas aeruginosa LNR1 for diesel biodegradation based on transcriptomic and proteomic.

Diesel, as a toxic and complex pollutant, is one of the main components in oily wastewater, and poses serious threats to the aquatic environment and the health of organisms. Employing environmentally friendly biostimulants to enhance the metabolic functions of microorganisms is currently the optimal choice to improve the biodegradation of oil-containing wastewater efficiency. This study takes Pseudomonas aeruginosa LNR1 as the target, analyzing the physiological responses and molecular mechanisms of biofilm formation when enhanced by the extracellular metabolites of euglena (EME) for diesel degradation. The results show that EME not only induces auto-aggregation behavior of strain LNR1, forming aerobic suspended granule biofilm, but also promotes the secretion of signaling molecules in the quorum sensing (QS) system. Transcriptomic and proteomic analyses indicate that the stimulatory effect of EME on strain LNR1 mainly manifests in biofilm formation, substance transmembrane transport, signal transduction, and other biological processes, especially the QS system in signal transduction, which plays a significant regulatory role in biofilm formation, chemotaxis, and two-component system (TCS). This study collectively unveils the molecular mechanisms of biostimulant EME inducing strain LNR1 to enhance diesel degradation from different aspects, providing theoretical guidance for the practical application of EME in oily wastewater pollution control.

Exploration of the mechanism of 2-CP degradation by Acinetobacter sp. stimulated by Lactobacillus plantarum fermentation waste: A bio-waste reuse.

Green and economical pollution management methods which reusing bio-waste as biostimulant to effectively improve the removal of target pollutants are receiving more and more attention. In this study, Lactobacillus plantarum fermentation waste solution (LPS) was used to investigate its facilitative effect and the stimulation mechanisms on the degradation of 2-chlorophenol (2-CP) by strain Acinetobacter sp. strain ZY1 in terms of both cell physiology and transcriptomics. The degradation efficiency of 2-CP was improved from 60% to > 80% under LPS treatment. The biostimulant maintained the morphology of strain, reduced the level of reactive oxygen species, and recovered the cell membrane permeability from 39% to 22%. It also significantly increased the level of electron transfer activity and extracellular polymeric substances secretion and improved the metabolic activity of the strain. The transcriptome results revealed the stimulation of LPS to promote biological processes such as bacterial proliferation, metabolism, membrane structure composition, and energy conversion. This study provided new insights and references for the reuse of fermentation waste streams in biostimulation methods.

Development of a three-step-based novel strategy integrating DMPK with network pharmacology and bioactivity evaluation for the discovery of Q-markers of traditional Chinese medicine prescriptions: Danlou tablet as an example.

BACKGROUND: Quality marker (Q-marker) serves an important role in promoting the standardization of the quality of traditional Chinese medicine (TCM) prescriptions. However, discovering comprehensive and representative Q-markers from TCM prescriptions composed of multiple components remains difficult. PURPOSE: A three-step-based novel strategy integrating drug metabolism and pharmacokinetics (DMPK) with network pharmacology and bioactivity evaluation was proposed to discover the Q-markers and applied to a research example of Danlou tablet (DLT), a famous TCM prescription with remarkable and reliable clinical effects for coronary heart disease (CHD). METHODS: Firstly, the metabolic profile in vivo of DLT was systemically characterized, and the pharmacokinetic (PK) properties of PK markers were then investigated. Secondly, an integrated network of "PK markers - CHD targets - pathways - therapeutic effects" was established to screen out the crucial PK markers of DLT against CHD. Thirdly, the crucial PK markers that could exhibit strong myocardial protection activity in the H9c2 cardiomyocyte model were selected as the candidate Q-markers of DLT. According to the proportion of their Cmax value in vivo, the candidate Q-markers were configured into a composition; the bioactivity was then evaluated to confirm their synergistic effect and justify their usage as Q-markers. RESULTS: First of all, a total of 110 DLT-related xenobiotics (35 prototypes and 75 metabolites) were detected in bio-samples, and the pharmacokinetic properties of 13 PK markers of DLT were successfully characterized, revealing the quality transitivity and traceability from prescription to in vivo. Then, 6 crucial PK markers with three topological features (degree, betweenness, and closeness) greater than the average values in the pharmacology network were screened out as the key components of DLT against CHD. Furthermore, among these 6 crucial PK markers, 5 components (puerarin, alisol A, daidzein, paeoniflorin, and tanshinone IIA) with strong myocardial protection activity were chosen as the candidate Q-markers to constitute a new composition. The composition activated the expression of the PI3K/AKT pathway and exhibited strong myocardial protection activity, and the effective concentrations (nM level) of these components in the composition were significantly lower than their individually effective concentrations (µM level), indicating that there was a certain synergistic effect between them. Hence, the 5 components with multiple properties, including testability, quality transitivity and traceability from prescription to in vivo, effectiveness, and compatibility contribution, were defined as comprehensive and representative Q-markers of DLT. CONCLUSION: This study not only presented a novel idea for the revelation of comprehensive and representative Q-markers in quality control research of TCM prescriptions, but also identified the reasonable Q-markers of DLT for the first time to improve the quality control level of DLT.

Using Polygenic Risk Scores Related to Complex Traits to Predict Production Performance in Cross-Breeding of Yeast.

The cultivation of hybrids with favorable complex traits is one of the important goals for animal, plant, and microbial breeding practices. A method that can closely predict the production performance of hybrids is of great significance for research and practice. In our study, polygenic risk scores (PRSs) were introduced to estimate the production performance of Saccharomyces cerevisiae. The genetic variation of 971 published isolates and their growth ratios under 35 medium conditions were analyzed by genome-wide association analysis, and the precise p-value threshold for each phenotype was calculated. Risk markers for the above 35 phenotypes were obtained. By estimating the genotype of F1 hybrids according to that of the parents, the PRS of 613 F1 hybrids was predicted. There was a significant linear correlation between the maximum growth rate at 40 °C and PRS in F1 hybrids and their parents (R2 = 0.2582, R2 = 0.2414, respectively), which indicates that PRS can be used to estimate the production performance of individuals and their hybrids. Our method can provide a reference for strain selection and F1 prediction in cross-breeding yeasts, reduce workload, and improve work efficiency.

De Novo Whole-Genome Sequencing and Assembly of the Yellow-Throated Bunting (Emberiza elegans) Provides Insights into Its Evolutionary Adaptation.

Yellow-throated bunting is a small migratory songbird unique to the Palearctic region. However, the genetic studies of this species remain limited, with no nuclear genomic sequence reported to date. In this study, the genomic DNA from the bird was sequenced in long reads using Nanopore sequencing technology. Combining short-read sequencing, the genome was well-assembled and annotated. The final length of the assembly is approximately 1.14 Gb, with a scaffold N50 of 28.94 Mb. About 15,868 protein-coding genes were predicted, and 16.62% of the genome was identified as having repetitive elements. Comparative genomic analysis showed numerous expanded gene families and positively selected genes significantly enriched in those KEGG pathways that are associated with migratory behavior adaptation and immune response. Here, this newly generated de novo genome of the yellow-throated bunting using long reads provide the research community with a valuable resource for further studies of population genetic diversity and genome evolution in this species.

Dopamine D2 receptors in the nucleus accumbens modulate erectile function in a rat model of nonorganic erectile dysfunction.

BACKGROUND: The central molecular mechanisms of nonorganic erectile dysfunction remains unknown. OBJECTIVE: This study aimed to investigate the association of dopaminergic neurons projecting to the nucleus accumbens of male rats with nonorganic erectile dysfunction. MATERIALS/METHODS: Nonorganic erectile dysfunction was induced by chronic mild stress. The sucrose consumption test, sexual behavior test, and apomorphine test were carried out to select depression-like rats with erectile dysfunction. These rats were considered as nonorganic erectile dysfunction model rats. Dopamine D1/D2 receptor agonist/antagonist was infused into the nucleus accumbens to observe the effect on sexual behavior. Dopaminergic projections to the nucleus accumbens were labeled with both the retrograde tracer FluoroGold injected into the nucleus accumbens and tyrosine hydroxylase. The expression level of tyrosine hydroxylase in dopaminergic neurons projecting to the nucleus accumbens in the ventral tegmental area was measured. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the nucleus accumbens were also measured. RESULTS: Nonorganic erectile dysfunction was proved by the sucrose consumption test, sexual behavior test, and apomorphine test in model rats. After central infusion of the dopamine D2 receptor agonist into the nucleus accumbens, the recovery of erectile function, sexual arousal, and motivation were indicated by increased intromission ratio and decreased mount latency. Decreased expression levels of dopamine D2 receptors and tyrosine hydroxylase in the nucleus accumbens and decreased expression level of tyrosine hydroxylase in the dopaminergic neurons projecting to the nucleus accumbens were observed in model rats. DISCUSSION: These results suggest the impairment of dopaminergic neurons projecting to the nucleus accumbens and dopamine D2 signaling in the nucleus accumbens, causing the suppression of erectile function, sexual arousal, and motivation. CONCLUSION: These results suggest that the impaired dopamine D2 receptor pathway in the nucleus accumbens may be one of the main pathway involved in the development of nonorganic erectile dysfunction in the present model.

[A simplified technique for reconstruction of vesicourethral support in laparoscopic radical prostatectomy improves immediate continence].

OBJECTIVE: To investigate the application of a simplified technique for reconstruction of vesicourethral support (RVUS) in laparoscopic radical prostatectomy (LRP). METHODS: From January 2017 to August 2019, 122 patients with localized prostate cancer underwent extraperitoneal LRP, 65 with RVUS (the RVUS group) and 57 without RVUS (the non-RVUS group). We compared the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, incidence of urethrovesical anastomotic urinary leakage (UVAUL), postoperative urinary continence, postoperative hospital stay, intraperitoneal drainage tube removal time, and urethral catheter removal time between the two groups of patients. RESULTS: No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, or urethral catheter removal time (P > 0.05). The incidence rate of UVAUL was lower in the non-RVUS than in the RVUS group (8.8% vs 0%, P < 0.05), and so were the rates of postoperative urinary continence immediate after (0% vs 32.3%, P < 0.05) and at 1 month (38.6% vs 56.9%, P < 0.05), 3 months (59.6% vs 80%, P < 0.05), 6 months (78.9% vs 84.6%, P > 0.05) and 12 months after catheter removal (87.7% vs 92.3%, P > 0.05). The postoperative hospital stay was dramatically longer in the non-RVUS than in the RVUS group (ï¼»9.1 ± 4.3ï¼½ vs ï¼»6.7 ± 1.8ï¼½ d, P < 0.01) and so was the intraperitoneal drainage tube removal time (ï¼»6.9 ± 4.5ï¼½ vs ï¼»4.8 ± 1.5ï¼½ d, P < 0.01). CONCLUSIONS: The simplified technique for reconstruction of vesicourethral support in laparoscopic radical prostatectomy improves early urinary continence, especially immediate continence, decreases the incidence rate of urethrovesical anastomotic urinary leakage, and shortens the intraperitoneal drainage tube removal time and postoperative hospital stay.?

Spatial dynamics of Chinese Muntjac related to past and future climate fluctuations.

Climate fluctuations in the past and in the future are likely to result in population expansions, shifts, or the contraction of the ecological niche of many species, and potentially leading to the changes in their geographical distributions. Prediction of suitable habitats has been developed as a useful tool for the assessment of habitat suitability and resource conservation to protect wildlife. Here, we model the ancestral demographic history of the extant modern Chinese Muntjac Muntiacus reevesi populations using approximate Bayesian computation (ABC) and used the maximum entropy model to simulate the past and predict the future spatial dynamics of the species under climate oscillations. Our results indicated that the suitable habitats for the M. reevesi shifted to the Southeast and contracted during the Last Glacial Maximum, whereas they covered a broader and more northern position in the Middle Holocene. The ABC analyses revealed that the modern M. reevesi populations diverged in the Middle Holocene coinciding with the significant contraction of the highly suitable habitat areas. Furthermore, our predictions suggest that the potentially suitable environment distribution for the species will expand under all future climate scenarios. These results indicated that the M. reevesi diverged in the recent time after the glacial period and simultaneously as its habitat's expanded in the Middle Holocene. Furthermore, the past and future climate fluctuation triggered the change of Chinese muntjac spatial distribution, which has great influence on the Chinese muntjac's population demographic history.

Detoxification of azo dye Direct Black G by thermophilic Anoxybacillus sp. PDR2 and its application potential in bioremediation.

Direct Black G (DBG) is a highly toxic synthetic azo dye which is difficult to degrade. Biological treatment seems to be a promising option for the treatment of azo dye containing effluent. A thermophilic bacterial strain (Anoxybacillus sp. PDR2) previously isolated from the soil can effectively remove DBG. However, the molecular underpinnings of DBG degradation and the microbial detoxification ability remains unknown. In the present study, the genetic background of PDR2 for the efficient degradation of DBG and its adaptation to azo dye-contaminated environments was revealed by bioinformatics. Moreover, the possible biodegradation pathways were speculated based on the UV-vis spectral analysis, FTIR, and intermediates identified by LC-MS. Additionally, phytotoxicity and the comet experiment studies clearly indicated that PDR2 converts toxic azo dye (DBG) into low toxicity metabolites. The combination of biodegradation pathways and detoxification analysis were utilized to explore the molecular degradation mechanism and bioremediation of azo dye for future applications. These findings will provide a valuable theoretical basis for the practical treatment of azo dye wastewater.

Evaluation of bioremediation and detoxification potentiality for papermaking black liquor by a new isolated thermophilic and alkali-tolerant Serratia sp. AXJ-M.

There is a great need for efficiently treating papermaking black liquor because it can seriously pollute both soil and water ecosystems. In this study, the Plackett-Burman (PB) experimental design combined with response surface methodology (RSM) was used for improving the biodegradation efficiency of lignin by a new isolated thermophilic and alkali-tolerant strain Serratia sp. AXJ-M, and the results showed that a biodegradation efficiency of 70.5% was achieved under optimal culture conditions. The bacterium with ligninolytic activities significantly decreased target the parameters (color 80%, lignin 60%, phenol 95%, BOD 80% and COD 80%). The control and treated samples were analyzed by gas chromatography-mass spectrometer (GC-MS), which showed that the concentrations of a majority of low-molecular-weight compounds were decreased after biological treatment. Furthermore, toxicological, genotoxicity and phytotoxicity studies have supported the detoxification by the bacterium of black liquor. Finally, the genome sequence of the thermophilic, alkali-tolerant and lignin-degrading bacterium AXJ-M was completed, and the genetic basis of the thermophilic and alkali-resistant properties of AXJ-M was preliminarily revealed. The dyp-type peroxidase was first reported to have the potential to catalyze lignin degradation structurally. These findings suggest that Serratia sp. AXJ-M may be potentially useful for bioremediation applications for papermaking black liquor.

[Hydrogen-rich water improves progressive sperm motility in rats by reducing oxidative stress and upregulating CLDN3 and SRD5A2 expressions].

Objective: To investigate the protective effect of long-term consumption of hydrogen-rich water (HRW) on the percentage of progressively motile sperm (PMS) in male rats. METHODS: Twenty normal healthy male SD rats were equally randomized into an HRW and a control group, the former given HRW (1.2 ppm) and the latter normal saline, both intragastrically at 2 ml/d for 9 months. Then, the bilateral epididymides of the rats were harvested for preparation of sperm suspension and detection of the percentage of PMS. The testis tissue was isolated for HE staining and determination of the expressions of the Ki67, CYBB, eNOS, CLDN3 and SRD5A2 proteins using the streptavidin-peroxidase (SP) immunohistochemical method. RESULTS: The percentage of PMS was significantly higher in the HRW than in the control group (ï¼»64.3 ± 4.7ï¼½% vs ï¼»55.3 ± 9.5ï¼½%, P < 0.05), and so was the expression of Ki67 in the testicular tissue (P < 0.01). Compared with the controls, the rats in the HRW group showed markedly decreased oxidative stress-related index CYBB (P < 0.01), increased eNOS level (P < 0.01), and upregulated expressions of sperm development-related proteins CLDN3 and SRD5A2 (P < 0.01 and P < 0.05). CONCLUSIONS: Hydrogen not only regulates the expressions of some oxidative stress-related indicators, but also increases the expressions of the molecules promoting sperm maturation and motility, which provides a theoretical basis and experimental support for the application and studies of hydrogen in asthenospermia.

Association of MMP-9 polymorphisms with diabetic nephropathy risk: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is a multifactorial disease with gene-environment interaction resulting in progressive renal function damage. Multiple studies have assessed the association between matrix metalloproteinase-9 (MMP-9) gene promoter polymorphism and DN susceptibility. However, the results are inconclusive. In the present study, we will conduct a meta-analysis to further examine this relationship more precisely. METHODS: Electronic databases (Pubmed, Web of Science, Embase, Google Scholar, Wanfang, China Biological Medicine and China National Knowledge Infrastructure) will be used to search clinical case-control studies about MMP-9 polymorphism and DN published until 18 August 2020. The language will be restricted to Chinese and English. Two reviewers will take charge of completing the selection of study, the extraction of data as well as the assessment of study quality independently. The Newcastle-Ottawa Scale will be used to evaluate the study quality. We will evaluate the association under 5 genetic models. Fixed-effects or random-effects models will be used to calculate the effect sizes of odds ratio and 95% confidence intervals. Afterwards, subgroup analysis will be conducted in terms of the ethnicity and genotyping method. Additionally, sensitivity analysis will be performed via sequentially omitting each of the included studies one at a time. The funnel plots, Egger regression test, and Begg rank correlation test will be used to test the potential publication bias. All the statistical analyses will be performed using Review Manager 5.3 and Stata 12.0. RESULTS: This protocol reported according to the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. This study will provide a better understanding of the association between MMP-9 polymorphisms and DN risk. CONCLUSION: Publishing this protocol will minimize the potential bias related to data mining, thus contributing to generation of reliable evidence. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/H5FS4.

Genome and transcriptome analysis of a newly isolated azo dye degrading thermophilic strain Anoxybacillus sp.

Understanding azo dye degrading enzymes and the encoding of their functional genes is crucial for the elucidation of their molecular mechanisms. In this study, a thermophilic strain capable of degrading azo dye was isolated from the soil near a textile dye manufacturing factory. Based on its morphological, physiological and biochemical properties, as well as 16S rRNA gene sequence analysis, the strain was identified as Anoxybacillus sp. PDR2. The decolorization ratios of 100-600 mg/L Direct Black G (DBG) by strain PDR2 reached 82.12-98.39% within 48 h of dyes. Genome analysis revealed that strain PDR2 contains a circular chromosome of 3791144 bp with a G + C content of 42.48%. The genetic basis of azo dye degradation by strain PDR2 and its capacity to adapt to harsh environments, were further elucidated through bioinformatics analysis. RNA-Seq and qRT-PCR technology confirmed that NAD(P)H-flavin reductase, 2Fe-2S ferredoxin and NAD(P)-dependent ethanol dehydrogenase genes expressed by strain PDR2, were the key genes involved in DBG degradation. The combination of genome and transcriptome analysis was utilized to explore the key genes of strain PDR2 involved in azo dye biodegradation, with these findings providing a valuable theoretical basis for the practical treatment of azo dye wastewater.

Integrated metagenomic and metaproteomic analyses reveal potential degradation mechanism of azo dye-Direct Black G by thermophilic microflora.

Direct Black G (DBG) is a typical toxic azo dye with extensive applications but it poses a serious threat to the aquatic ecosystem and humans. It is necessary to efficiently and safely remove DBG from environments by the application of various treatment technologies. A thermophilic microflora previously isolated from the soil can effectively metabolize DBG. However, the molecular basis of DBG degradation by this thermophilic microflora remains unknown. In this study, metagenomic sequencing technology and qRT-PCR have been used to elucidate the functional potential of genes and their modes of action on DBG. A quantitative metaproteomic method was further utilized to identify the relative functional proteins involved. Subsequently, the possible co-metabolic molecular mechanisms of DBG degradation by candidate genes and functional proteins of the thermophilic microflora were illustrated. The combination of metagenomics and metaproteomics to investigate the degradation of DBG by a microflora was reported for the first time in recent literature; this can further provide a deep insight into the molecular degradation mechanism of dye pollutants by natural microflora.

Veliparib overcomes multidrug resistance in liver cancer cells.

Overexpression of ATP-binding cassette (ABC) transporter is one of the most important factors taking responsibility for the progress of multidrug resistance (MDR) in multiple cancers. In this study, we investigated that veliparib, a PARP inhibitor which is in clinical development, could overcome ABCB1-mediated MDR in liver cancer cells. Veliparib could significantly enhance the cytotoxic effects of a series of conventional chemotherapeutic drugs in ABCB1-overexpression liver cancer cells. Mechanism study showed that veliparib could significantly enhance the accumulation of doxorubicin in ABCB1-overexpression liver cancer cells, without down-regulating the expression level of ABCB1. Finally, veliparib could significantly inhibit the ATPase activity of ABCB1 transporter. This study could provide information that combine veliparib with other chemotherapeutic drugs may benefit liver cancer patients.

Exploration of the key functional strains from an azo dye degradation microbial community by DGGE and high-throughput sequencing technology.

This study investigated a previously developed thermophilic microbial community with the ability to effectively degrade azo dyes. To identify the key microbes of this microbial community, a dilution-to-extinction approach was combined with polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and Illumina high-throughput sequencing technology (HTST). Strains belonging to Tepidiphilus sp. almost disappeared from the degradation solution at dilution ratios above 10-7; furthermore, at this ratio, the diluted microbial community almost lost their decolorization ability, indicating this ratio as the critical point for effective azo dye decolorization. Strains belonging to Tepidiphilus sp. were indicated as possible key functional microbes of this microbial community for effective azo dye decolorization. Moreover, the synergistic action of other microbes, such as Anoxybacillus sp., Clostridium sp., and Bacillus sp., was suggested to further promote the decolorization process by secreting azoreductase and laccase. Caloramator spp. were found have the ability to degrade proteins and amino acids, which might promote the degradation process with further degradation microbes. The loss of these bacteria might diminish the synergistic relationships among different strains, which further results in the failure of efficient azo dye decolorization and degradation by this microbial community.

Correction: Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats.

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Genome-wide Association Study of 24-Hour Urinary Excretion of Calcium, Magnesium, and Uric Acid.

OBJECTIVES: The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined. METHODS: Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume). RESULTS: One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near TRPM6, whose protein product mediates magnesium transport in the colon and kidney, and C9orf40, C9orf41, NMRK1, and OSTF1 (rs1176815; P=1.70×10-14, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; P=1.12×10-8) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs. CONCLUSION: Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.

Dopamine D2 receptors in the basolateral amygdala modulate erectile function in a rat model of nonorganic erectile dysfunction.

Nonorganic erectile dysfunction is a problem with unknown central mechanisms. Changes in brain activity in the amygdala have been observed in human patients. This study aimed to investigate the dopamine system in the basolateral amygdala of male rats with nonorganic erectile dysfunction. We applied chronic mild stress to induce nonorganic erectile dysfunction. After exposure to chronic mild stress, the sucrose consumption test, sexual behaviour test and apomorphine test were used to select depression-like rats with erectile dysfunction as nonorganic erectile dysfunction model rats. The sexual behaviour of these rats after central infusion of a dopamine D1/D2 receptor agonist/antagonist was observed. The expression levels of dopamine D1/D2 receptors and tyrosine hydroxylase in the basolateral amygdala were also measured. The result of the sucrose consumption test, sexual behaviour test and apomorphine test indicated a successful nonorganic erectile dysfunction model. Central infusion of a dopamine D2 receptor agonist increased intromission ratio in model rats. Lower expression levels of tyrosine hydroxylase and the dopamine D2 receptor in the basolateral amygdala were observed in rats with nonorganic erectile dysfunction. These results suggest that impairment of the dopamine D2 receptor pathway in the basolateral amygdala may contribute to the development of nonorganic erectile dysfunction.