Comparison of soil-test extractants for potassium, calcium, magnesium, sulfur, and micronutrients in Idaho soils

Soil fertility and nutrient-management programs across Idaho and the western United States need to consider the effective comparison of various extractants for nutrient analysis. Common extractants for primary (potassium; K), secondary (calcium; Ca, magnesium; Mg, sulfur; S) and micro (zinc; Zn, copper; Cu, manganese; Mn, iron; Fe, aluminum; Al, boron; B, sodium; Na,)-nutrients vary (e.g., ammonium acetate, AA, Olsen). The desire to develop relationships among common tests in the region and those of multinutrient extractants used or proposed in other geographical regions has increased due to the interest in soil health measurements (Mehlich-3; M-3 and Haney, Haney, Hossner, Arnold; H3A). To investigate these multinutrient tests, 46 primarily alkaline soils were sampled from the 0 to 30-cm depth in agricultural fields in Idaho. The majority of nutrients were highly related and relationships were developed. However, for Ca issues were noted for M-3 due to high levels of calcium carbonate in the soil interfering with the test on alkaline soils. Additionally, issues were noted for specific micronutrients when both acidic and alkaline soils were combined in the analysis, but were improved when they were separated. Thus, this research provides specific correlation equations that could be used for comparison among tests as well as provides evidence of the potential suitability of multinutrient extractants in the region

Evaluation of soil test phosphorus extractants in Idaho soils

Evaluation of soil-phosphorus (P) tests is critical to ensure the accuracy of fertilizer recommendations to optimize crop yield while minimizing negative environmental consequences. Olsen-P is the most commonly used soil-P test for alkaline calcareous soils found in Idaho and the Western United States. The Bray-1 test is commonly used in the Pacific Northwest (PNW) on neutral to acidic soils but underestimates P in alkaline calcareous soils. Mehlich-3 has been evaluated throughout various regions in the United States. Little data evaluating the test exists on soils in the Western United States. Additionally, the comparatively newly developed H3A test, a component of the soil health tool, has not been widely evaluated on alkaline calcareous soils. Soil samples from the 0- to 30-cm depth were collected from agricultural fields throughout Idaho and analyzed using Bray-1, H3A, Mehlich-3, and Olsen P extractants. Results suggested that Olsen P was strongly correlated with Mehlich-3, while Bray-1 and H3A were not correlated with Olsen P. Both the Bray-1 and H3A test underestimated extractable P when compared with the Olsen P test, whereas the Mehlich-3 overestimated. A threshold point in calcium carbonate (i.e., inorganic carbon (IC)) of 6.7 and 5.1 mg kg-1 for the Bray-1 and H3A was obtained, respectively, that indicated inorganic carbon concentrations at or above these levels result in underestimation of extractable soil P. Thus, Mehlich-3 was very strongly correlated to Olsen P and could be evaluated for use in alkaline calcareous soils whereas Bray-1 and H3A have notable issues that would limit their applicability

MetropolJS: Visualizing and debugging large-scale JavaScript program structure with treemaps

As a result of the large scale and diverse composition of modern compiled JavaScript applications, comprehending overall program structure for debugging is challenging. In this paper we present our solution: MetropolJS. By using a Treemap-based visualization it is possible to get a high level view within limited screen real estate. Previous approaches to Treemaps lacked the fine detail and interactive features to be useful as a debugging tool. This paper introduces an optimized approach for visualizing complex program structure that enables new debugging techniques where the execution of programs can be displayed in real time from a bird's-eye view. The approach facilitates highlighting and visualizing method calls and distinctive code patterns on top of code segments without a high overhead for navigation. Using this approach enables fast analysis of previously difficult-to-comprehend code bases

The number of flags in finite vector spaces: Asymptotic normality and Mahonian statistics

We study the generalized Galois numbers which count flags of length r in N-dimensional vector spaces over finite fields. We prove that the coefficients of those polynomials are asymptotically Gaussian normally distributed as N becomes large. Furthermore, we interpret the generalized Galois numbers as weighted inversion statistics on the descent classes of the symmetric group on N elements and identify their asymptotic limit as the Mahonian inversion statistic when r approaches infinity. Finally, we apply our statements to derive further statistical aspects of generalized Rogers-Szegoe polynomials, re-interpret the asymptotic behavior of linear q-ary codes and characters of the symmetric group acting on subspaces over finite fields, and discuss implications for affine Demazure modules and joint probability generating functions of descent-inversion statistics.Comment: 19 pages. Corrected proof of asymptotic normality (Theorem 3.5). Previous Proposition 3.3 is fals

Secondary education reform in Lesotho and Zimbabwe and the needs of rural girls: Pronouncements, policy and practice

Analysis of the educational needs of rural girls in Lesotho and Zimbabwe suggests a number of shortcomings in the current form of secondary education, and ways in which it might be modified so as to serve this sizeable group of students better. Several of the shortcomings, notably in relation to curricular irrelevance and excessive focus on examinations, have long been recognised, including by politicians. Yet political pronouncements are seldom translated into policy, and even where policy is formulated, reforms are seldom implemented in schools. This paper makes use of interviews with educational decision-makers in the two southern African countries and a range of documentary sources to explore why, despite the considerable differences between the two contexts, much needed educational reforms have been implemented in neither

Natural product derivative Gossypolone inhibits Musashi family of RNA-binding proteins

Background: The Musashi (MSI) family of RNA-binding proteins is best known for the role in post-transcriptional regulation of target mRNAs. Elevated MSI1 levels in a variety of human cancer are associated with up-regulation of Notch/Wnt signaling. MSI1 binds to and negatively regulates translation of Numb and APC (adenomatous polyposis coli), negative regulators of Notch and Wnt signaling respectively. Methods: Previously, we have shown that the natural product (-)-gossypol as the first known small molecule inhibitor of MSI1 that down-regulates Notch/Wnt signaling and inhibits tumor xenograft growth in vivo. Using a fluorescence polarization (FP) competition assay, we identified gossypolone (Gn) with a > 20-fold increase in Ki value compared to (-)-gossypol. We validated Gn binding to MSI1 using surface plasmon resonance, nuclear magnetic resonance, and cellular thermal shift assay, and tested the effects of Gn on colon cancer cells and colon cancer DLD-1 xenografts in nude mice. Results: In colon cancer cells, Gn reduced Notch/Wnt signaling and induced apoptosis. Compared to (-)-gossypol, the same concentration of Gn is less active in all the cell assays tested. To increase Gn bioavailability, we used PEGylated liposomes in our in vivo studies. Gn-lip via tail vein injection inhibited the growth of human colon cancer DLD-1 xenografts in nude mice, as compared to the untreated control (P < 0.01, n = 10). Conclusion: Our data suggest that PEGylation improved the bioavailability of Gn as well as achieved tumor-targeted delivery and controlled release of Gn, which enhanced its overall biocompatibility and drug efficacy in vivo. This provides proof of concept for the development of Gn-lip as a molecular therapy for colon cancer with MSI1/MSI2 overexpression

Natural product (-)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1

Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21WAF-1. We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells. We used a fluorescence polarization assay to screen for small molecules that disrupt the binding of MSI1 to its consensus RNA binding site. One of the top hits was (-)-gossypol (Ki = 476 ± 273 nM), a natural product from cottonseed, known to have potent anti-tumor activity and which has recently completed Phase IIb clinical trials for prostate cancer. Surface plasmon resonance and nuclear magnetic resonance studies demonstrate a direct interaction of (-)-gossypol with the RNA binding pocket of MSI1. We further showed that (-)-gossypol reduces Notch/Wnt signaling in several colon cancer cell lines having high levels of MSI1, with reduced SURVIVIN expression and increased apoptosis/autophagy. Finally, we showed that orally administered (-)-gossypol inhibits colon cancer growth in a mouse xenograft model. Our study identifies (-)-gossypol as a potential small molecule inhibitor of MSI1-RNA interaction, and suggests that inhibition of MSI1's RNA binding activity may be an effective anti-cancer strategy

Sulfonylpiperazine compounds prevent Plasmodium falciparum invasion of red blood cells through interference with actin-1/profilin dynamics

Published: April 13, 2023With emerging resistance to frontline treatments, it is vital that new antimalarial drugs are identified to target Plasmodium falciparum. We have recently described a compound, MMV020291, as a specific inhibitor of red blood cell (RBC) invasion, and have generated analogues with improved potency. Here, we generated resistance to MMV020291 and performed whole genome sequencing of 3 MMV020291-resistant populations. This revealed 3 nonsynonymous single nucleotide polymorphisms in 2 genes; 2 in profilin (N154Y, K124N) and a third one in actin-1 (M356L). Using CRISPR-Cas9, we engineered these mutations into wild-type parasites, which rendered them resistant to MMV020291. We demonstrate that MMV020291 reduces actin polymerisation that is required by the merozoite stage parasites to invade RBCs. Additionally, the series inhibits the actin-1-dependent process of apicoplast segregation, leading to a delayed death phenotype. In vitro cosedimentation experiments using recombinant P. falciparum proteins indicate that potent MMV020291 analogues disrupt the formation of filamentous actin in the presence of profilin. Altogether, this study identifies the first compound series interfering with the actin-1/profilin interaction in P. falciparum and paves the way for future antimalarial development against the highly dynamic process of actin polymerisation.Madeline G. Dans, Henni Piirainen, William Nguyen, Sachin Khurana, Somya Mehra, Zahra Razook, Niall D. Geoghegan, Aurelie T. Dawson, Sujaan Das, Molly Parkyn Schneider, Thorey K. Jonsdottir, Mikha Gabriela, Maria R. Gancheva, Christopher J. Tonkin, Vanessa Mollard, Christopher Dean Goodman, Geoffrey I. McFadden, Danny W. Wilson, Kelly L. Rogers, Alyssa E. Barry, Brendan S. Crabb, Tania F. de Koning-Ward, Brad E. Sleebs, Inari Kursula, Paul R. Gilso

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes