Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study)

Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study).BackgroundHyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients.MethodsTo determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus ≤5.5mg/dL and Ca × P product ≤55mg2/dL2, we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients.ResultsComparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08mg/dL difference, P = 0.0006), higher serum calcium (0.63mg/dL difference, P < 0.0001), and lower Ca × P (6.1mg2/dL2 difference, P = 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28–4.37, P = 0.0058], and 15% to 20% more likely to attain goal Ca × P (OR 2.16, 95% CI 1.20–3.86, P = 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8–13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001).ConclusionCalcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients

A polymorphism associated with depressive disorders differentially regulates brain derived neurotrophic factor promoter IV activity

PMCID: PMC3712170Peer reviewedPublisher PD

The Chandra Source Catalog

The Chandra Source Catalog (CSC) is a general purpose virtual X-ray astrophysics facility that provides access to a carefully selected set of generally useful quantities for individual X-ray sources, and is designed to satisfy the needs of a broad-based group of scientists, including those who may be less familiar with astronomical data analysis in the X-ray regime. The first release of the CSC includes information about 94,676 distinct X-ray sources detected in a subset of public ACIS imaging observations from roughly the first eight years of the Chandra mission. This release of the catalog includes point and compact sources with observed spatial extents <~ 30''. The catalog (1) provides access to the best estimates of the X-ray source properties for detected sources, with good scientific fidelity, and directly supports scientific analysis using the individual source data; (2) facilitates analysis of a wide range of statistical properties for classes of X-ray sources; and (3) provides efficient access to calibrated observational data and ancillary data products for individual X-ray sources, so that users can perform detailed further analysis using existing tools. The catalog includes real X-ray sources detected with flux estimates that are at least 3 times their estimated 1 sigma uncertainties in at least one energy band, while maintaining the number of spurious sources at a level of <~ 1 false source per field for a 100 ks observation. For each detected source, the CSC provides commonly tabulated quantities, including source position, extent, multi-band fluxes, hardness ratios, and variability statistics, derived from the observations in which the source is detected. In addition to these traditional catalog elements, for each X-ray source the CSC includes an extensive set of file-based data products that can be manipulated interactively.Comment: To appear in The Astrophysical Journal Supplement Series, 53 pages, 27 figure

Mitigation of phosphorus, sediment and Escherichia coli losses in runoff from a dairy farm roadway

peer reviewedDairy cow deposits on farm roadways are a potential source of contaminants entering streams. Phosphorus (P), suspended sediment (SS) and Escherichia coli (E. coli) loads in 18 runoff events over 12 mo from two-halves of a section of dairy farm roadway that spilt into an adjacent P-impacted stream were measured. The runoff from one half was untreated while the other half was directed through a filter of steel melter slag [termed aluminium chlorohydrate (ACH)-altered slag] sprayed with 1% ACH solution to improve P sorption capacity. An uncertainty analysis was conducted to ascertain potential loads of P lost from roadways considering variation in deposit weight, number and P content. Over the monitoring period, the total load decreased P (92%), SS (98%) and E. coli (76%) from the ACHaltered slag roadway compared to the control. However, uncertainty analysis showed that the amount of dung-P deposited on the roadway could be 10-fold greater

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.

Modelling the impacts of agricultural management practices on river water quality in Eastern England

Agricultural diffuse water pollution remains a notable global pressure on water quality, posing risks to aquatic ecosystems, human health and water resources and as a result legislation has been introduced in many parts of the world to protect water bodies. Due to their efficiency and cost-effectiveness, water quality models have been increasingly applied to catchments as Decision Support Tools (DSTs) to identify mitigation options that can be introduced to reduce agricultural diffuse water pollution and improve water quality. In this study, the Soil and Water Assessment Tool (SWAT) was applied to the River Wensum catchment in eastern England with the aim of quantifying the long-term impacts of potential changes to agricultural management practices on river water quality. Calibration and validation were successfully performed at a daily time-step against observations of discharge, nitrate and total phosphorus obtained from high-frequency water quality monitoring within the Blackwater sub-catchment, covering an area of 19.6 km2. A variety of mitigation options were identified and modelled, both singly and in combination, and their long-term effects on nitrate and total phosphorus losses were quantified together with the 95% uncertainty range of model predictions. Results showed that introducing a red clover cover crop to the crop rotation scheme applied within the catchment reduced nitrate losses by 19.6%. Buffer strips of 2 m and 6 m width represented the most effective options to reduce total phosphorus losses, achieving reductions of 12.2% and 16.9%, respectively. This is one of the first studies to quantify the impacts of agricultural mitigation options on long-term water quality for nitrate and total phosphorus at a daily resolution, in addition to providing an estimate of the uncertainties of those impacts. The results highlighted the need to consider multiple pollutants, the degree of uncertainty associated with model predictions and the risk of unintended pollutant impacts when evaluating the effectiveness of mitigation options, and showed that high-frequency water quality datasets can be applied to robustly calibrate water quality models, creating DSTs that are more effective and reliable

Antibiotic activities of peptides, hydrogen peroxide and peroxynitrite in plant defence

Genes encoding plant antibiotic peptides show expression patterns that are consistent with a defence role. Transgenic over-expression of defence peptide genes is potentially useful to engineer resistance of plants to relevant pathogens. Pathogen mutants that are sensitive to plant peptides in vitro have been obtained and a decrease of their virulence in planta has been observed, which is consistent with their hypothetical defence role. A similar approach has been followed to elucidate the potential direct anti-microbial role of hydrogen peroxide. Additionally, a scavenger of peroxynitrite has been used to investigate its involvement in plant defenc

Drought tolerance in Pinus halepensis seed sources as identified by distinctive physiological and molecular markers

[EN] Drought is one of the main constraints determining forest species growth, survival and productivity, and therefore one of the main limitations for reforestation or afforestation. The aim of this study is to characterize the drought response at the physiological and molecular level of different Pinus halepensis (common name Aleppo pine) seed sources, previously characterized in field trials as drought-sensitive or drought-tolerant. This approach aims to identify different traits capable of predicting the ability of formerly uncharacterized seedlings to cope with drought stress. Gas-exchange, water potential, photosynthetic pigments, soluble sugars, free amino acids, glutathione and proteomic analyses were carried out on control and drought-stressed seedlings in greenhouse conditions. Gas-exchange determinations were also assessed in field-planted seedlings in order to validate the greenhouse experimental conditions. Drought-tolerant seed sources presented higher values of photosynthetic rates, water use efficiency, photosynthetic pigments and soluble carbohydrates concentrations. We observed the same pattern of variation of photosynthesis rate and maximal efficiency of PSII in field. Interestingly drought-tolerant seed sources exhibited increased levels of glutathione, methionine and cysteine. The proteomic profile of drought tolerant seedlings identified two heat shock proteins and an enzyme related to methionine biosynthesis that were not present in drought sensitive seedlings, pointing to the synthesis of sulfur amino acids as a limiting factor for drought tolerance in Pinus halepensis. Our results established physiological and molecular traits useful as distinctive markers to predict drought tolerance in Pinus halepensis provenances that could be reliably used in reforestation programs in drought prone areas.This study is a part of the research project: "Application of molecular biology techniques in forest restoration in Mediterranean environments, PAID-05-11" funded by the Universitat Politecnica de Valencia (UPV), program for supporting R&D of new multidisciplinary research lines. The authors are grateful to the Ministerio de Economia y Competitividad AGL2014-57431-P. AV was supported by project Survive-2 (CGL2015-69773-C2-2-P MINECO/FEDER) by the Spanish Government and Prometeo program (DESESTRES-Generalitat Valenciana). CEAM is funded by Generalitat Valenciana.Taïbi, K.; Campo García, ADD.; Vilagrosa, A.; Belles Albert, JM.; López-Gresa, MP.; Pla, D.; Calvete Chornet, JJ.... (2017). Drought tolerance in Pinus halepensis seed sources as identified by distinctive physiological and molecular markers. Frontiers in Plant Science. 8:1-13. https://doi.org/10.3389/fpls.2017.01202S1138Alcázar, R., Altabella, T., Marco, F., Bortolotti, C., Reymond, M., Koncz, C., … Tiburcio, A. F. (2010). Polyamines: molecules with regulatory functions in plant abiotic stress tolerance. Planta, 231(6), 1237-1249. doi:10.1007/s00425-010-1130-0Atzmon, N., Moshe, Y., & Schiller, G. (2004). Ecophysiological response to severe drought in Pinus halepensis Mill. trees of two provenances. Plant Ecology (formerly Vegetatio), 171(1/2), 15-22. doi:10.1023/b:vege.0000029371.44518.38Baquedano, F. J., & Castillo, F. J. (2006). Comparative ecophysiological effects of drought on seedlings of the Mediterranean water-saver Pinus halepensis and water-spenders Quercus coccifera and Quercus ilex. Trees, 20(6), 689-700. doi:10.1007/s00468-006-0084-0Baquedano, F. J., Valladares, F., & Castillo, F. J. (2008). Phenotypic plasticity blurs ecotypic divergence in the response of Quercus coccifera and Pinus halepensis to water stress. European Journal of Forest Research, 127(6), 495-506. doi:10.1007/s10342-008-0232-8Bartlett, M. K., Scoffoni, C., & Sack, L. (2012). The determinants of leaf turgor loss point and prediction of drought tolerance of species and biomes: a global meta-analysis. Ecology Letters, 15(5), 393-405. doi:10.1111/j.1461-0248.2012.01751.xBradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1-2), 248-254. doi:10.1016/0003-2697(76)90527-3Chen, H., & Jiang, J.-G. (2010). Osmotic adjustment and plant adaptation to environmental changes related to drought and salinity. Environmental Reviews, 18(NA), 309-319. doi:10.1139/a10-014Cuesta, B., Villar-Salvador, P., Puértolas, J., Jacobs, D. F., & Rey Benayas, J. M. (2010). Why do large, nitrogen rich seedlings better resist stressful transplanting conditions? A physiological analysis in two functionally contrasting Mediterranean forest species. Forest Ecology and Management, 260(1), 71-78. doi:10.1016/j.foreco.2010.04.002Duncan, D. B. (1955). Multiple Range and Multiple F Tests. Biometrics, 11(1), 1. doi:10.2307/3001478Eichel, J., Gonzalez, J. C., Hotze, M., Matthews, R. G., & Schroder, J. (1995). Vitamin-B12-Independent Methionine Synthase from a Higher Plant (Catharanthus Roseus). Molecular Characterization, Regulation, Heterologous Expression, and Enzyme Properties. European Journal of Biochemistry, 230(3), 1053-1058. doi:10.1111/j.1432-1033.1995.tb20655.xFayos, J., Bellés, J. M., López-Gresa, M. P., Primo, J., & Conejero, V. (2006). Induction of gentisic acid 5-O-β-d-xylopyranoside in tomato and cucumber plants infected by different pathogens. Phytochemistry, 67(2), 142-148. doi:10.1016/j.phytochem.2005.10.014Franck, N., Vaast, P., Genard, M., & Dauzat, J. (2006). Soluble sugars mediate sink feedback down-regulation of leaf photosynthesis in field-grown Coffea arabica. Tree Physiology, 26(4), 517-525. doi:10.1093/treephys/26.4.517Freeman, J. L., Persans, M. W., Nieman, K., Albrecht, C., Peer, W., Pickering, I. J., & Salt, D. E. (2004). Increased Glutathione Biosynthesis Plays a Role in Nickel Tolerance in Thlaspi Nickel Hyperaccumulators. The Plant Cell, 16(8), 2176-2191. doi:10.1105/tpc.104.023036Golldack, D., Li, C., Mohan, H., & Probst, N. (2014). Tolerance to drought and salt stress in plants: Unraveling the signaling networks. Frontiers in Plant Science, 5. doi:10.3389/fpls.2014.00151Gomez-Garay, A., Lopez, J. A., Camafeita, E., Bueno, M. A., & Pintos, B. (2013). Proteomic perspective of Quercus suber somatic embryogenesis. Journal of Proteomics, 93, 314-325. doi:10.1016/j.jprot.2013.06.006Groppa, M. D., & Benavides, M. P. (2007). Polyamines and abiotic stress: recent advances. Amino Acids, 34(1), 35-45. doi:10.1007/s00726-007-0501-8Grossnickle, S. C. (2012). Why seedlings survive: influence of plant attributes. New Forests, 43(5-6), 711-738. doi:10.1007/s11056-012-9336-6He, C.-Y., Zhang, J.-G., Duan, A.-G., Sun, H.-G., Fu, L.-H., & Zheng, S.-X. (2007). Proteins responding to drought and high-temperature stress in Pinus armandii Franch. Canadian Journal of Botany, 85(10), 994-1001. doi:10.1139/b07-085Hu, B., Simon, J., Kuster, T. M., Arend, M., Siegwolf, R., & Rennenberg, H. (2012). Nitrogen partitioning in oak leaves depends on species, provenance, climate conditions and soil type. Plant Biology, 15, 198-209. doi:10.1111/j.1438-8677.2012.00658.xKlein, T., Di Matteo, G., Rotenberg, E., Cohen, S., & Yakir, D. (2012). Differential ecophysiological response of a major Mediterranean pine species across a climatic gradient. Tree Physiology, 33(1), 26-36. doi:10.1093/treephys/tps116Labudda, M., & Safiul Azam, F. M. (2014). Glutathione-dependent responses of plants to drought: a review. Acta Societatis Botanicorum Poloniae, 83(1), 3-12. doi:10.5586/asbp.2014.003Leck, M. A., Parker, V. T., & Simpson, R. L. (Eds.). (2008). Seedling Ecology and Evolution. doi:10.1017/cbo9780511815133Lichtenthaler, H. K. (1987). [34] Chlorophylls and carotenoids: Pigments of photosynthetic biomembranes. Plant Cell Membranes, 350-382. doi:10.1016/0076-6879(87)48036-1Maestre, F. T., & Cortina, J. (2004). Are Pinus halepensis plantations useful as a restoration tool in semiarid Mediterranean areas? Forest Ecology and Management, 198(1-3), 303-317. doi:10.1016/j.foreco.2004.05.040Margolis, H. A., & Brand, D. G. (1990). An ecophysiological basis for understanding plantation establishment. Canadian Journal of Forest Research, 20(4), 375-390. doi:10.1139/x90-056Martinez-Ferri, E., Balaguer, L., Valladares, F., Chico, J. M., & Manrique, E. (2000). Energy dissipation in drought-avoiding and drought-tolerant tree species at midday during the Mediterranean summer. Tree Physiology, 20(2), 131-138. doi:10.1093/treephys/20.2.131Maxwell, K., & Johnson, G. N. (2000). Chlorophyll fluorescence—a practical guide. Journal of Experimental Botany, 51(345), 659-668. doi:10.1093/jxb/51.345.659McDowell, N. G. (2011). Mechanisms Linking Drought, Hydraulics, Carbon Metabolism, and Vegetation Mortality. Plant Physiology, 155(3), 1051-1059. doi:10.1104/pp.110.170704Mordukhova, E. A., & Pan, J.-G. (2013). Evolved Cobalamin-Independent Methionine Synthase (MetE) Improves the Acetate and Thermal Tolerance of Escherichia coli. Applied and Environmental Microbiology, 79(24), 7905-7915. doi:10.1128/aem.01952-13Mulet, J. M., Alemany, B., Ros, R., Calvete, J. J., & Serrano, R. (2004). Expression of a plant serine O-acetyltransferase inSaccharomyces cerevisiae confers osmotic tolerance and creates an alternative pathway for cysteine biosynthesis. Yeast, 21(4), 303-312. doi:10.1002/yea.1076Mulet, J. M., Martin, D. E., Loewith, R., & Hall, M. N. (2006). Mutual Antagonism of Target of Rapamycin and Calcineurin Signaling. Journal of Biological Chemistry, 281(44), 33000-33007. doi:10.1074/jbc.m604244200Patakas, A., Nikolaou, N., Zioziou, E., Radoglou, K., & Noitsakis, B. (2002). The role of organic solute and ion accumulation in osmotic adjustment in drought-stressed grapevines. Plant Science, 163(2), 361-367. doi:10.1016/s0168-9452(02)00140-1Peguero-Pina, J. J., Sancho-Knapik, D., Barrón, E., Camarero, J. J., Vilagrosa, A., & Gil-Pelegrín, E. (2014). Morphological and physiological divergences within Quercus ilex support the existence of different ecotypes depending on climatic dryness. Annals of Botany, 114(2), 301-313. doi:10.1093/aob/mcu108Peguero-Pina, J. J., Sisó, S., Flexas, J., Galmés, J., Niinemets, Ü., Sancho-Knapik, D., & Gil-Pelegrín, E. (2017). Coordinated modifications in mesophyll conductance, photosynthetic potentials and leaf nitrogen contribute to explain the large variation in foliage net assimilation rates across Quercus ilex provenances. Tree Physiology, 37(8), 1084-1094. doi:10.1093/treephys/tpx057Pinheiro, C., António, C., Ortuño, M. F., Dobrev, P. I., Hartung, W., Thomas-Oates, J., … Wilson, J. C. (2011). Initial water deficit effects on Lupinus albus photosynthetic performance, carbon metabolism, and hormonal balance: metabolic reorganization prior to early stress responses. Journal of Experimental Botany, 62(14), 4965-4974. doi:10.1093/jxb/err194Pyngrope, S., Bhoomika, K., & Dubey, R. S. (2012). Reactive oxygen species, ascorbate–glutathione pool, and enzymes of their metabolism in drought-sensitive and tolerant indica rice (Oryza sativa L.) seedlings subjected to progressing levels of water deficit. Protoplasma, 250(2), 585-600. doi:10.1007/s00709-012-0444-0Rodríguez-Calcerrada, J., Pérez-Ramos, I. M., Ourcival, J.-M., Limousin, J.-M., Joffre, R., & Rambal, S. (2011). Is selective thinning an adequate practice for adapting Quercus ilex coppices to climate change? Annals of Forest Science, 68(3), 575-585. doi:10.1007/s13595-011-0050-xRuiz-Yanetti, S., Chirino, E., & Bellot, J. (2016). Daily whole-seedling transpiration determined by minilysimeters, allows the estimation of the water requirements of seedlings used for dryland afforestation. Journal of Arid Environments, 124, 341-351. doi:10.1016/j.jaridenv.2015.08.017Sánchez-Gómez, D., Majada, J., Alía, R., Feito, I., & Aranda, I. (2010). Intraspecific variation in growth and allocation patterns in seedlings of Pinus pinaster Ait. submitted to contrasting watering regimes: can water availability explain regional variation? Annals of Forest Science, 67(5), 505-504. doi:10.1051/forest/2010007Serrano, R., Mulet, J. M., Rios, G., Marquez, J. A., Larrinoa, I. igo F. de, Leube, M. P., … Montesinos, C. (1999). A glimpse of the mechanisms of ion homeostasis during salt stress. Journal of Experimental Botany, 50(Special_Issue), 1023-1036. doi:10.1093/jxb/50.special_issue.1023Taïbi, K., del Campo, A. D., Aguado, A., & Mulet, J. M. (2015). The effect of genotype by environment interaction, phenotypic plasticity and adaptation on Pinus halepensis reforestation establishment under expected climate drifts. Ecological Engineering, 84, 218-228. doi:10.1016/j.ecoleng.2015.09.005Taïbi, K., del Campo, A. D., Mulet, J. M., Flors, J., & Aguado, A. (2014). Testing Aleppo pine seed sources response to climate change by using trial sites reflecting future conditions. New Forests, 45(5), 603-624. doi:10.1007/s11056-014-9423-yVerbruggen, N., & Hermans, C. (2008). Proline accumulation in plants: a review. Amino Acids, 35(4), 753-759. doi:10.1007/s00726-008-0061-6Vilagrosa, A., Cortina, J., Gil-Pelegrin, E., & Bellot, J. (2003). Suitability of Drought-Preconditioning Techniques in Mediterranean Climate. Restoration Ecology, 11(2), 208-216. doi:10.1046/j.1526-100x.2003.00172.xVilagrosa, A., Morales, F., Abadía, A., Bellot, J., Cochard, H., & Gil-Pelegrin, E. (2010). Are symplast tolerance to intense drought conditions and xylem vulnerability to cavitation coordinated? An integrated analysis of photosynthetic, hydraulic and leaf level processes in two Mediterranean drought-resistant species. Environmental and Experimental Botany, 69(3), 233-242. doi:10.1016/j.envexpbot.2010.04.013Voss, I., Sunil, B., Scheibe, R., & Raghavendra, A. S. (2013). Emerging concept for the role of photorespiration as an important part of abiotic stress response. Plant Biology, 15(4), 713-722. doi:10.1111/j.1438-8677.2012.00710.xWhite, T. L., Adams, W. T., & Neale, D. B. (Eds.). (2007). Forest genetics. doi:10.1079/9781845932855.0000Williams, M. I., & Dumroese, R. K. (2013). Preparing for Climate Change: Forestry and Assisted Migration. Journal of Forestry, 111(4), 287-297. doi:10.5849/jof.13-016Zhang, Y.-J., Sack, L., Cao, K.-F., Wei, X.-M., & Li, N. (2017). Speed versus endurance tradeoff in plants: Leaves with higher photosynthetic rates show stronger seasonal declines. Scientific Reports, 7(1). doi:10.1038/srep4208

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors)