Oxalate-Induced Damage to Renal Tubular Cells

Our own studies and those of others have shown that the incidence of calcium oxalate stones and plaques is markedly increased by nephrotoxins. The possible role of oxalate as a nephrotoxin has not been fully appreciated. However, recent studies in experimental animals and in cultured cells support this possibility. The results of these studies led us to hypothesize that hyperoxaluria promotes stone formation in several ways: by providing a substrate for the formation of the most common form of renal stones, calcium oxalate stones, and by inducing damage to renal epithelial cells. Damaged cells in turn would produce an environment favorable for crystal retention and provide membranous debris that promotes crystal nucleation, aggregation and adherence. The present report summarizes evidence for oxalate nephrotoxicity and discusses the potential importance of oxalate toxicity in the pathogenesis of stone disease

Population genetic structure associated with a landscape barrier in the Western Grasswren (Amytornis textilis textilis)

Dispersal patterns can dictate genetic population structure and, ultimately, population resilience, through maintaining gene flow and genetic diversity. However, geographical landforms, such as peninsulas, can impact dispersal patterns and thus be a barrier to gene flow. Here, we use 13 375 genome-wide single-nucleotide polymorphisms (SNPs) to evaluate genetic population structure and infer dispersal patterns of the Western Grasswren Amytornis textilis textilis (WGW, n = 140) in the Shark Bay region of Western Australia. We found high levels of genetic divergence between subpopulations on the mainland (Hamelin) and narrow peninsula (Peron). In addition, we found evidence of further genetic sub-structuring within the Hamelin subpopulation, with individuals collected from the western and eastern regions of a conservation reserve forming separate genetic clusters. Spatial autocorrelation analysis within each subpopulation revealed significant local-scale genetic structure up to 35 km at Hamelin and 20 km at Peron. In addition, there was evidence of male philopatry in both subpopulations. Our results suggest a narrow strip of land may be acting as a geographical barrier in the WGW, limiting dispersal between a peninsula and mainland subpopulation. In addition, heterogeneous habitat within Hamelin may be restricting dispersal at the local scale. Furthermore, there is evidence to suggest that the limited gene flow is asymmetrical, with directional dispersal occurring from the bounded peninsula subpopulation to the mainland. This study highlights the genetic structure existing within and between some of the few remaining WGW subpopulations, and shows a need to place equal importance on conservation efforts to maintain them in the future

Allele-Selective Suppression of Mutant Huntingtin in Primary Human Blood Cells

Post-transcriptional gene silencing is a promising therapy for the monogenic, autosomal dominant, Huntington\u27s disease (HD). However, wild-type huntingtin (HTT) has important cellular functions, so the ideal strategy would selectively lower mutant HTT while sparing wild-type. HD patients were genotyped for heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or mutant HTT. Primary ex vivo myeloid cells were isolated from heterozygous patients and transfected with SNP-targeted siRNA, using glucan particles taken up by phagocytosis. Highly selective mRNA knockdown was achieved when targeting each allele of rs362331 in exon 50 of the HTT transcript; this selectivity was also present on protein studies. However, similar selectivity was not observed when targeting rs362273 or rs362307. Furthermore, HD myeloid cells are hyper-reactive compared to control. Allele-selective suppression of either wild-type or mutant HTT produced a significant, equivalent reduction in the cytokine response of HD myeloid cells to LPS, suggesting that wild-type HTT has a novel immune function. We demonstrate a sequential therapeutic process comprising genotyping and mutant HTT-linkage of SNPs, followed by personalised allele-selective suppression in a small patient cohort. We further show that allele-selectivity in ex vivo patient cells is highly SNP-dependent, with implications for clinical trial target selection

A Model for Solving the Optimal Water Allocation Problem in River Basins with Network Flow Programming When Introducing Non-Linearities

[EN] The allocation of water resources between different users is a traditional problem in many river basins. The objective is to obtain the optimal resource distribution and the associated circulating flows through the system. Network flow programming is a common technique for solving this problem. This optimisation procedure has been used many times for developing applications for concrete water systems, as well as for developing complete decision support systems. As long as many aspects of a river basin are not purely linear, the study of non-linearities will also be of great importance in water resources systems optimisation. This paper presents a generalised model for solving the optimal allocation of water resources in schemes where the objectives are minimising the demand deficits, complying with the required flows in the river and storing water in reservoirs. Evaporation from reservoirs and returns from demands are considered, and an iterative methodology is followed to solve these two non-network constraints. The model was applied to the Duero River basin (Spain). Three different network flow algorithms (Out-of-Kilter, RELAX-IVand NETFLO) were used to solve the allocation problem. Certain convergence issues were detected during the iterative process. There is a need to relate the data from the studied systems with the convergence criterion to be able to find the convergence criterion which yields the best results possible without requiring a long calculation time.We thank the Spanish Ministry of Economy and Competitivity (Comision Interministerial de Ciencia y Tecnologia, CICYT) for funding the projects INTEGRAME (contract CGL2009-11798) and SCARCE (program Consolider-Ingenio 2010, project CSD2009-00065). We also thank the European Commission (Directorate-General for Research & Innovation) for funding the project DROUGHT-R&SPI (program FP7-ENV-2011, project 282769). And last, but not least, to the Fundacion Instituto Euromediterraneo del Agua with the project "Estudio de Adaptaciones varias del modelo de optimizacion de gestiones de recursos hidricos Optiges".Haro Monteagudo, D.; Paredes Arquiola, J.; Solera Solera, A.; Andreu Álvarez, J. (2012). A Model for Solving the Optimal Water Allocation Problem in River Basins with Network Flow Programming When Introducing Non-Linearities. Water Resources Management. 26(14):4059-4071. https://doi.org/10.1007/s11269-012-0129-7S405940712614Ahuja R, Magnanti T, Orlin J (1993) Network flows: theory, algorithms and applications. Prentice Hall, New YorkAndreu J, Capilla J, Sanchís E (1996) AQUATOOL, a generalized decision-support system for water resources planning and operational management. 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J Water Resour Plan Manag 124:69–78Harou JJ, Medellín-Azuara J, Zhu T et al (2010) Economic consequences of optimized water management for a prolonged, severe drought in California. Water Resour Res 46:W05522Hsu N, Cheng K (2002) Network Flow Optimization Model for Basin-Scale Water Supply Planning. J Water Resour Plan Manag 128:102–112Ilich N (1993) Improvement of the return flow allocation in the Water Resources Management Model of Alberta Environment. Can J Civ Eng 20:613–621Ilich N (2009) Limitations of network flow algorithms in river basin modeling. J Water Resour Plan Manag 135:48–55Kennington JL, Helgason RV (1980) Algorithms for network programming. John Wiley and Sons, New YorkKhaliquzzaman, Chander S (1997) Network flow programming model for multireservoir sizing. J Water Resour Plan Manag 123:15–21Kuczera G (1989) Fast Multireservoir Mulltiperiod Linear Programming Models. Water Resour Res 25:169–176Kuczera G (1993) Network linear programming codes for water-supply headworks modeling. J Water Resour Plan Manag 119:412–417Labadie J (2004) Optimal operation of multireservoir systems: state-of-the-art review. J Water Resour Plan Manag 130:93–111Labadie J (2006) MODSIM: river basin management decision support system. In: Singh W, Frevert D (eds) Watershed models. CRC, Boca Raton, pp 569–592Labadie J, Baldo M, Larson R (2000) MODSIM: decision support system for river basin management. Documentation and user manual. Dept. Of Civil Engineering, CSU, Fort CollinsManca A, Sechi G, Zuddas P (2010) Water supply network optimisation using equal flow algorithms. Water Resour Manag 24:3665–3678MMA (2000) Libro blanco del agua en España. Ministerio de Medio Ambiente, Secretaría general Técnica, Centro de PublicacionesMMA (2008) Confederación Hidrográfica del Duero. Memoria 2008. http://www.chduero.es/Inicio/Publicaciones/tabid/159/Default.aspx . 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Impacts of climate change on harmful algal blooms

High biomass Harmful Algal Blooms (HABs) such as Karenia mikimotoi and shellfish toxin producing HAB species continue to be observed in UK and Republic of Ireland waters. Regional differences continue to be seen in the distribution of HABs in UK and RoI waters with impacts mainly observed in the south and west coast of Ireland and regions in the UK with a strong Atlantic influence, e.g. Regions 1, 3, 4, 6 and 7. There is little monitoring aside from the continuous plankton recorder (CPR) in Region 8. The impacts from HABs in Wales, Northern Ireland and the Isle of Man are generally low. Since the last MCCIP report card was issued, blooms of Karenia mikimotoi have caused problems in Ayrshire, Scotland, and also in the north-west coast of Ireland where concerns about the quantity of dead wild fish washing on shore during an event in Ireland in 2012 resulted in two beaches being closed to the public. No clear trend that can be attributed to climate change can be observed in the incidence of shellfish toxin producing HABs since the last report card was issued. During the last two years the incidence of some shellfish toxins has continued to decrease (e.g. paralytic shellfish poisoning toxins in Scotland). High concentrations of yessotoxins (YTX) and azaspiracids (AZAs) have been recorded for the first time in Scotland. Northern Ireland enforced its first shellfish harvesting closure for high concentrations of domoic acid (the toxin responsible for amnesic shellfish poisoning, ASP) in 2012. A recent survey in Scottish waters (Regions 1, 6 and 7) has revealed the presence of domoic acid in the urine and faeces of harbour seals (Phoca vitulina). The impacts of these toxins on the health of marine mammals are unknown and a more detailed study is currently being undertaken. Many of the future impacts of climate change are unknown. Increasing sea surface temperatures as a result of climate change may increase the potential for blooms of species that are not currently found in UK and RoI waters through range expansion or human mediated introduction. There is evidence that no new HAB species have become established during the last two years. An increase in the duration of stratification of the water column may influence the abundance of HABs in UK and RoI waters. This is particularly relevant in shelf areas and Region 8, an area where offshore high biomass K. mikimotoi blooms have been hypothesized to initiate and impact coastal areas along the west of Ireland and Regions 6, 7 and 1. Conversely, an increase in wind speed and duration may reduce the duration of stratification in the water column. This may result in a decrease of some HAB dinoflagellate species and an increase in HAB diatom species. Little is known about the impacts of ocean acidification or changes in offshore circulation on the incidence of HABs. The role of offshore blooms in seeding coastal blooms (e.g. of K. mikimotoi) remains unknown and the lack of monitoring in Region 8 and on the shelf edge compounds this knowledge gap

Confirmation of a new resonance in 26Si and contribution of classical novae to the galactic abundance of 26Al

© 2023 The Author(s). Published by the American Physical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The 25Al(p ,γ ) reaction has long been highlighted as a possible means to bypass the production of 26Al cosmic γ rays in classical nova explosions. However, uncertainties in the properties of key resonant states in 26Si have hindered our ability to accurately model the influence of this reaction in such environments. We report on a detailed γ -ray spectroscopy study of 26Si and present evidence for the existence of a new, likely ℓ =1 , resonance in the 25Al + p system at Er=153.9 (15 ) keV. This state is now expected to provide the dominant contribution to the 25Al(p ,γ ) stellar reaction rate over the temperature range, T ≈0.1 −0.2 GK. Despite a significant increase in the rate at low temperatures, we find that the final ejected abundance of 26Al from classical novae remains largely unaffected even if the reaction rate is artificially increased by a factor of 10. Based on new, galactic chemical evolution calculations, we estimate that the maximum contribution of novae to the observed galactic abundance of 26Al is ≈0.2 M⊙ . Finally, we briefly highlight the important role that super-asymptotic giant branch stars may play in the production of 26Al.Peer reviewe

Identification of polymorphic inversions from genotypes

Background: Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. Results: We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data [1], utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS). Conclusions: We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model [2]. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU) and Yoruba (YRI) HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions previously predicted by independent experimental methods in ten (9+1) individuals [3,4]. We provide efficient implementations of both genotype and haplotype methods as a unified R package inveRsion

How and Why Chromosome Inversions Evolve

Chromosome inversions are a major engine of genome evolution. New genomic and ecological data are beginning to reveal the evolutionary forces that drive the evolution of inversions

Search for Nova Presolar Grains: γ -Ray Spectroscopy of Ar 34 and its Relevance for the Astrophysical Cl 33 (p,γ) Reaction

The discovery of presolar grains in primitive meteorites has initiated a new era of research in the study of stellar nucleosynthesis. However, the accurate classification of presolar grains as being of specific stellar origins is particularly challenging. Recently, it has been suggested that sulfur isotopic abundances may hold the key to definitively identifying presolar grains with being of nova origins and, in this regard, the astrophysical Cl33(p,γ)Ar34 reaction is expected to play a decisive role. As such, we have performed a detailed γ-ray spectroscopy study of Ar34. Excitation energies have been measured with high precision and spin-parity assignments for resonant states, located above the proton threshold in Ar34, have been made for the first time. Uncertainties in the Cl33(p,γ) reaction have been dramatically reduced and the results indicate that a newly identified ℓ =0 resonance at Er=396.9(13) keV dominates the entire rate for T=0.25-0.40 GK. Furthermore, nova hydrodynamic simulations based on the present work indicate an ejected S32/S33 abundance ratio distinctive from type-II supernovae and potentially compatible with recent measurements of a presolar grain