Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo

Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC–derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC–derived EVs are a heterogeneous population, ranging in size from that of micro–vesicles (150 nm–1 μm) down to that of exosomes (60–150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60–150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL–6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)–derived EVs previously described, suppressing T cell response to activation. The finding that USC–derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.     

The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd]_u and [NAG]_u) to the urine creatinine concentration ([cr]_u). In theory, the sources of these errors are nullified by normalization of excretion rates (E_Cd and E_NAG) to creatinine clearance (C_cr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, E_x/E_cr and E_x/C_cr were calculated as [x]_u/[cr]_u and [x]_u[cr]_p/[cr]_u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m². In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(E_Cd/C_cr) and log(E_NAG/C_cr) than for log(E_Cd/E_cr) and log(E_NAG/E_cr). Doubling of E_Cd/C_cr and E_NAG/C_cr increased POR by 132% and 168%; doubling of E_Cd/E_cr and E_NAG/E_cr increased POR by 64% and 54%. As log(E_Cd/C_cr) rose, associations of eGFR with log(E_Cd/C_cr) and log(E_NAG/C_cr) became stronger, while associations of eGFR with log(E_Cd/E_cr) and log(E_NAG/E_cr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R² was consistently higher with normalization to C_cr. Our tabular and graphic analyses uniformly indicate that normalization to C_cr clarified relationships of E_Cd and E_NAG to eGFR.     

The annual cycle of Flehmen in black-tailed deer (Odocoileus hemionus columbianus)

Flehmen is a stereotyped response of ungulates and other mammals to urine. In black-tailed deer, Flehmen occurs typically in males (rarely in females), and its frequency shows an annual cycle. Flehmen in response to female urine was most frequent in November, and to male urine in January. The response minimum to both types of urine occurred in May. Fifty-five to 100% of initial responses to female urine resulted in Flehmen. The deer responded more often to female urine, and the difference between the responses to female and male urine increased from May to November. A male's own urine released Flehmen more often than did urine of other males. The response intensity varied with the spatial orientation of the male to the urinating female, and responses were usually limited to distances of 15 m or less.     

Relationships between ammonia volatilization and nitrogen fertilizer application rate,intake and excretion of herbage nitrogen by cattle on grazed swards

Grazed pastures emit ammonia (NH₃) into the atmosphere; the size of the NH₃ loss appears to be related to nitrogen (N) application rate.The micrometeorological mass balance method was used to measure NH₃ volatilization from rotationally grazed swards on three plots in the autumn of 1989 and throughout the 1990 growing season. The aim of the research was to derive a mathematical relationship between NH₃ volatilization and N application rate, which would vary between soil type and weather conditions. In both years the plots received a total of 250, 400 or 550 kg N ha^–1 as calcium ammonium nitrate (CAN) split over 6 to 8 dressings. The number of grazing cycles ranged from 7 to 9 for the three N plots.In the last two grazing cycles of 1989, NH₃ losses were 3.8, 12.0 and 14.7 kg N ha^–1 for the 250N, 400N and 550N plots, which was equivalent to 5.3%, 13.9% and 14.4% of the amount of N excreted on the sward, respectively. In 1990, NH₃ losses were 9.1, 27.0 and 32.8 kg N ha^–1 for the 250N, 400N and 550N plots, which was equivalent to 3.3%, 6.9% and 6.9% of the N excreted, respectively. Differences in urine composition between the plots were relatively small. Rainfall and sward management affected the size of the NH₃ volatilization rate. Volatilization of NH₃ was related to N excretion and N application rate.A calculation procedure is given to enable the estimation of NH₃ volatilization from N application rate. Adjustments can be made for grazing efficiency, grazing selectivity, N retention in milk and liveweight gain, concentrate N intake and milking duration. Losses of NH₃ increase progressively with an increase in N application rate until herbage yield reaches a maximum at an application rate of about 500 kg N ha^–1 yr^–1.     

Sex-identifying urine and molt signals in lobster (Homarus americanus)

During courtship, premolt female lobsters,Homarus americanus, choose a male and initiate a pair bond by repeated approaches to his shelter. The male allows such a female to share his shelter for about one week. This knowledge formed the basis to search for quantitative evidence for lobster sex pheromone(s) used in courtship: male cues to allow premolt females to identify a preferred male, and female cues to allow males to identify a premolt mature female. In each of four 1500-liter naturalistic aquaria, the behavioral responses of one female and two male lobsters to male and female lobster urine (0.5 ml) and body odor (20 ml) stimuli were observed. These stimuli were injected once or twice per day into a continuously flowing delivery tube attached to lobster shelters. Habituation to stimulus introduction—a serious problem in earlier experiments—was apparently avoided in the more natural social and physical environment we employed in these experiments. We demonstrated that male and female molt body odors contain different chemical substances: females responded to male molt body odor and males responded to female molt body odor but not vice versa. In general, male and female intermolt urine caused strong responses; however, females responded only weakly to male urine. This suggests that male and female urine are chemically different. Female urine and molt body odor caused a typically male high-on-legs response. These results show that molt body odors and intermolt urine contain sex-specific substances, which may be used in lobster courtship as well as other social interactions.     

Large-scale protein identification of human urine proteome by multi-dimensional LC and MS/MS

Urine is a human specimen that is easily obtained non-invasively for clinical diagnosis. We attempted to enhance the resolution of current human urine proteomes and construct a comprehensive reference database for advanced studies, such as the discovery of biomarkers for renal diseases. Multi-dimensional LC-MS/MS was coupled with de novo sequencing and database matching. The proposed approach improved the identification of not only the proteins, but also the post-translational sites of urinary proteins. We identified 165, 200 and 259 unique gene products in the urine proteomes from males, females and pregnant women, respectively. When all of the results were combined and the redundancies removed, a total of 1095 distinct peptides were identified. Of these, 1016 peptides were associated with 334 unique gene products. In this study, over 100 gene products, including some disease-related proteins, were detected in urine for the first time by proteomic approaches. Various proteins with novel post-translational hydroxylation were identified using the MASCOT program and de novo sequencing. All proteins with peptide information were summarized into a comprehensive urine protein database. We believe that this comprehensive urine proteome database will assist in the identification of urinary proteins/polypeptides whose spectra are difficult to interpret in the discovery of urinary biomarkers.     

人尿中活性物质的开发

本文叙述了近年来人尿中活性物质的开发状况,列举了从人尿中提取的11种生物药品及其应用,并提出今后发展的方向。     

某研发基地分质负压排水工程设计

传统城市排水模式存在混合稀释、末端处理、高耗水、高污染、资源流失等特征及缺陷.分质负压排水技术将污染程度不同的生活废水分开收集并单独处理,实现生活污水的源头控制与资源回收,符合可持续发展理念.文章对某研发基地A车间进行了分质负压排水方案设计,粪便水和尿液分别经过处理后可作为农田绿色肥料,而经处理后的杂排水亦可用于人工湿地景观水.另外,该方案中采用的负压粪尿分离便器比节水便器节省约90％冲厕水,能最大程度地实现节水;同时回收利用尿液中的N、P等营养元素与粪便中的有机物等营养物质,有效避免富营养化问题.经估算,该分质负压排水系统每天可节约用水约11 m3,每年节约水资源费用约1.6万元.     

Efficient adsorptive extraction materials by surface protein-imprinted polymer over silica gel for selective recognition/separation of human serum albumin from urine

In this study, we report the development of adsorptive extraction materials by surface protein-imprinted polymers (MIPs) over silica gel for selective recognition/separation of human serum albumin (HSA) from urine. The HSA-imprinted polymers prepared on silica particle had at interface between the silica gel and different MIPs greatly produced enrichment for the binding of protein from the urine. The solid-phase extraction of the optimized polymer layer was prepared by copolymerization of methacrylic acid (MAA), acrylamide (AAm), and dimethylaminoethylmethacrylate (DMAEMA) and a crosslinker methylenebisacrylamide (MBA) at the mole ratio of 1:158:88 (T:M:C) and showed moderate affinity (<10⁴ order M⁻¹) toward target protein HSA and selectivity. Four analogues, egg white albumin (EWA), bovine serum albumin (BSA), lysozyme (Lyz), and creatinine (Cre) were selected to study the binding efficiency of MIPs in single and binary protein solutions. We studied the influence on recognition ability for HSA and found that prepolymer mixture and matrix flexibility of the optimized thin polymer layer (35 ± 10 nm) on the submicrosilica particles. The high-binding affinity (Q_MIP, 86.7 mg g⁻¹) and fast kinetics (180 min) were observed for this synthesized HSA-MIP when compared with other reported HSA-MIPs in surface imprinting (5.9 and 11.3 mg g⁻¹) and epitope surface imprinting (46.6 mg g⁻¹) methods. We demonstrated the application in real and synthetic urine samples that the approach allowed the efficient adsorption of HSA in real urine (129.48 mg g⁻¹) is almost double to the binding of HSA in synthetic urine (67.84 mg g⁻¹). Apart from this, only minor interference of Cre (2.74 mg g⁻¹) was observed, eventhough Cre is the final metabolite in urine. These adsorptive submicrosilica materials have potential in the pharmaceutical industry and clinical analysis applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46894.     

The good,the bad and the ugly – three approaches to management of human waste in a high-mountain environment

Each year, millions of mountaineers visit high-mountain areas. They generate tonnes of faeces and cubic hectometres of urine annually. Thus, proper disposal of human waste is important for the conservation and appropriate management of high-mountain areas. The management can address the issue in three ways: the good (complete/non-invasive); the bad (partial/superficial); and the ugly (invasive). With use of those categories, 20 selected summits from different parts of the world have been evaluated, separately in respect to faeces and urine. It was expected that correct or incorrect disposal of human waste would depend on the changing altitude and/or development level. Disappointingly, the correlation between selection criteria (better or worse solution) and the increase of altitude does not exist. Similarly, the increase of the development level does not play a significant role, especially when urine is taken under consideration. The problem is more global than was thought. The paper makes recommendations which could lead to reduction of this problem.