Trimethylamine N-oxide (TMAO) is a naturally occurring protecting osmolyte that stabilizes the folded state of proteins and also counteracts the destabilizing effect of urea on protein stability. ...Experimentally, it has been inferred that TMAO is preferentially excluded from the vicinity of protein surfaces. Here, we combine computer modeling and experimental measurements to gain an understanding of the mechanism of the protecting effect of TMAO on proteins. We have developed an all-atom molecular model for TMAO that captures the exclusion of TMAO from model compounds and protein surfaces, as a consequence of incorporating realistic TMAO–water interactions through osmotic pressure measurements. Osmotic pressure measurements also suggest no significant attraction between urea and TMAO molecules in solution. To obtain an accurate potential for molecular simulations of protein stability in TMAO solutions, we have explored different ways of parametrizing the protein/osmolyte and osmolyte/osmolyte interactions by scaling charges and the strength of Lennard-Jones interactions and carried out equilibrium folding experiments of Trp-cage miniprotein in the presence of TMAO to guide the parametrization. Our calculations suggest a general principle for preferential interaction behavior of cosolvents with protein surfacespreferentially excluded osmolytes have repulsive self-interaction given by osmotic coefficient ϕ > 1, while denaturants, in addition to having attractive interactions with the proteins, have favorable self-interaction given by osmotic coefficient ϕ < 1, to enable preferential accumulation in the vicinity of proteins.
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IJS, KILJ, NUK, PNG, UL, UM
Protamines are small, highly positively charged peptides used to package DNA at very high densities in sperm nuclei. Tight DNA packing is considered essential for the minimization of DNA damage by ...mutagens and reactive oxidizing species. A striking and general feature of protamines is the almost exclusive use of arginine over lysine for the positive charge to neutralize DNA. We have investigated whether this preference for arginine might arise from a difference in DNA condensation by arginine and lysine peptides. The forces underlying DNA compaction by arginine, lysine, and ornithine peptides are measured using the osmotic stress technique coupled with X-ray scattering. The equilibrium spacings between DNA helices condensed by lysine and ornithine peptides are significantly larger than the interhelical distances with comparable arginine peptides. The DNA surface-to-surface separation, for example, is some 50% larger with polylysine than with polyarginine. DNA packing by lysine rich peptides in sperm nuclei would allow much greater accessibility to small molecules that could damage DNA. The larger spacing with lysine peptides is caused by both a weaker attraction and a stronger short-range repulsion relative to that of the arginine peptides. A previously proposed model for binding of polyarginine and protamine to DNA provides a convenient framework for understanding the differences between the ability of lysine and arginine peptides to assemble DNA.
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IJS, KILJ, NUK, PNG, UL, UM
Urban greening can potentially help mitigate heat-related mortality and flooding facing the >4 billion urban population worldwide. However, the geographical variation of the relative combined ...hydrological and thermal performance benefits of such interventions are unknown. Here we quantify globally, using a hydrological model, how climate-driven trade-offs exist between hydrological retention and cooling potential of urban greening such as green roofs and parks. Using a Budyko framework, we show that water retention generally increases with aridity in water-limited environments, while cooling potential favors energy-limited climates. Our models suggest that common urban greening strategies cannot yield high performance simultaneously for addressing both urban heat-island and urban flooding problems in most cities globally. Irrigation, if sustainable, may enhance cooling while maintaining retention performance in more arid locations. Increased precipitation variability with climate change may reduce performance of thinner green-infrastructure more quickly compared to greened areas with thicker soils and root systems. Our results provide a conceptual framework and first-order quantitative guide for urban development, renewal and policymaking.
The sustainability of limited freshwater resources in coastal settings requires an understanding of the processes that affect them. This is especially relevant for freshwater lenses of oceanic ...islands. Yet, these processes are often obscured by dynamic oceanic water levels that change over a range of timescales. We use regression deconvolution to estimate an oceanic response function (ORF) that accounts for how sea-level fluctuations affect measured groundwater levels, thus providing a clearer understanding of recharge and withdrawal processes. The method is demonstrated using sea-level and groundwater-level measurements on the island of Norderney in the North Sea (northwestern Germany). We expect that the method is suitable for any coastal groundwater system where it is important to understand processes that affect freshwater lenses or other coastal freshwater resources.
Background
This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid ...tumors.
Methods
The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction.
Results
Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers.
Conclusions
We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The dynamic distribution of thermal conditions present in saturated near-surface sediments have been widely utilised to quantify the flow of water. A rapidly increasing number of papers demonstrate ...that heat as a tracer is becoming an integral part of the toolbox used to investigate water flow in the environment. We summarise the existing body of research investigating natural and induced heat transport, and analyse the progression in fundamental and natural process understanding through the qualitative and quantitative use of heat as a tracer. Heat transport research in engineering applications partly overlaps with heat tracing research in the earth sciences but is more advanced in the fundamental understanding. Combining the findings from both areas can enhance our knowledge of the heat transport processes and highlight where research is needed. Heat tracing relies upon the mathematical heat transport equation which is subject to certain assumptions that are often neglected. This review reveals that, despite the research efforts to date, the capability of the Fourier-model applied to conductive–convective heat transport in water saturated natural materials has not yet been thoroughly tested. However, this is a prerequisite for accurate and meaningful heat transport modelling with the purpose of increasing our understanding of flow processes at different scales. This review reveals several knowledge gaps that impose significant limitations on practical applications of heat as a tracer of water flow. The review can be used as a guide for further research directions on the fundamental as well as the practical aspects of heat transport on various scales from the lab to the field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Short arginine-rich proteins called protamines mediate the near crystalline DNA packaging in most vertebrate sperm cells. Protamines are synthesized during spermiogenesis and condense the paternal ...genome into a transcriptionally inactive state in late-stage spermatids. Protamines from eutherian mammals, including bulls and humans, also contain multiple cysteine residues that form intra- and interprotamine sulfur-sulfur bonds during the final stages of sperm maturation. Although the cross-linked protamine network is known to stabilize the resulting nucleoprotamine structure, little is known about the role of disulfide bonds on DNA condensation in the mammalian sperm. Using small angle x-ray scattering, we show that isolated bull nuclei achieve slightly lower DNA packing densities compared to salmon nuclei despite salmon protamine lacking cysteine residues. Surprisingly, reduction of the intermolecular sulfur-sulfur bonds of bull protamine results in tighter DNA packing. Complete reduction of the intraprotamine disulfide bonds ultimately leads to decondensation, suggesting that disulfide-mediated secondary structure is also critical for proper protamine function. Lastly, comparison of multiple bull collections showed some to have aberrant x-ray scattering profiles consistent with incorrect disulfide bond formation. Together, these observations shed light on the biological functions of disulfide linkages for in vivo DNA packaging in sperm chromatin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Estimating groundwater recharge rates is important to understand and manage groundwater. Numerous studies have used collated recharge datasets to understand and project regional- or global-scale ...groundwater recharge rates. However, recharge estimation methods all have distinct assumptions, quantify different recharge components and operate over different temporal scales. We use over 200 000 groundwater chloride measurements to estimate groundwater recharge rates using an improved chloride mass balance (CMB) method across Australia. Groundwater recharge rates were produced stochastically using gridded chloride deposition, runoff and precipitation datasets. After filtering out groundwater recharge rates where the assumptions of the method may have been compromised, 98 568 estimates of recharge were produced. The resulting groundwater recharge rates and 17 spatial datasets were integrated into a random forest regression algorithm, generating a high-resolution (0.05°) model of groundwater recharge rates across Australia. The regression reveals that climate-related variables, including precipitation, rainfall seasonality and potential evapotranspiration, exert the most significant influence on groundwater recharge rates, with vegetation (the normalised difference vegetation index or NDVI) also contributing significantly. Importantly, the mean values of both the recharge point dataset (43.5 mm yr−1) and the spatial recharge model (22.7 mm yr−1) are notably lower than those reported in previous studies, underscoring the prolonged timescale of the CMB method, the potential disparities arising from distinct recharge estimation methodologies and limited averaging across climate zones. This study presents a robust and automated approach to estimate recharge using the CMB method, offering a unified model based on a single estimation method. The resulting datasets, the Python script for recharge rate calculation and the spatial recharge models collectively provide valuable insights for water resource management across the Australian continent, and similar approaches can be applied globally.
This paper develops a new fibre tracking algorithm to efficiently locate fibre centrelines (skeletons), from X-ray Computed Tomography (X-ray CT) images of carbon fibre reinforced polymer (CFRP), ...which are then used to generate micro-scale finite element models. Three-dimensional images with 330nmvoxel resolution of multidirectional +45/90/−45/0 CFRP specimens were obtained by fast synchrotron X-ray CT scanning. Conventional image processing techniques, such as a combination of filters, delineation of plies, binarisation of images, and fibre identification by local maxima and ultimate eroding points, were tried first but found insufficient to produce continuous fibre centrelines for segmentation, especially in regions with highly congested fibres. The new algorithm uses a global overlapping stack filtering step followed by a local fibre tracking step. Both steps are based on the Bayesian inference theory. The new algorithm is found capable of efficiently define fibre centrelines for the generation of micro-scale finite element models with high fidelity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A review of heat and solute transport in sediments demonstrates that the use of heat as a tracer has not been experimentally evaluated under the same experimental conditions as those used for the ...evaluation of solute as a tracer. Furthermore, there appears to be disagreement in the earth science literature over the significance of the thermal dispersivity term. To help resolve this disagreement, detailed experimentation with typical groundwater flow velocities (Darcy range, Re < 2.5) was conducted in a specifically designed hydraulic tank containing well‐sorted saturated sand. The experiment enabled, for the first time, the precise monitoring of heat and solute tracer movement from a point source in separate runs under identical solid matrix and steady state flow conditions. Experimental results demonstrate that heat transport with natural groundwater flow velocities can reach a transition zone between conduction and convection (0.5 < Pet < 2.5). The thermal dispersion behavior can be described by using a thermal dispersivity coefficient and the square of the thermal front velocity. We propose an empirical formulation for thermal dispersion with Darcy flow in natural porous media and clarify the disagreement regarding its significance. Finally, it was observed that Darcy velocities independently derived from heat and solute experimentation show a systematic discrepancy of up to 20%, and that experimental thermal dispersion results contain significant scatter.
Key Points
Clarification how thermal dispersivity should be used
Detailed experimental comparison between heat and solute transport in sand
Comparison of heat and solute transport models
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BFBNIB, CEKLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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