496 research outputs found
Soil-related habitat specialization in dipterocarp rain forest tree species in Borneo
Summary 1 We conducted a field experiment to test whether aggregated spatial distributions were related to soil variation in locally sympatric tree species in the rain forests of Sarawak, Malaysia. Dryobalanops aromatica , Shorea laxa , and Swintonia schwenkii are naturally aggregated on low-fertility humult ultisols, Dryobalanops lanceolata and Hopea dryobalanoides on moderate-fertility udult ultisols and Shorea balanocarpoides is found on both soil types. 2 Seedlings of all six species were grown in a nested-factorial experiment for 20 months in humult and udult soils in gaps and in the understorey to test for soil-specific differences in performance. Phosphorus addition was used to test for effects due to P-limitation. 3 Four species showed significantly higher growth on their natural soils, but one humultsoil species ( D. aromatica ) and the broadly distributed species were not significantly affected by soil type. 4 One udult-soil species, D. lanceolata , had both lower relative growth rate and lower mycorrhizal colonization on humult soil. However, humult soils also had lower levels of Ca, Mg, K, N and probably water availability. 5 The overall ranking of growth rates among species was similar on the two soils. Growth rates were strongly positively correlated with leaf area ratio and specific leaf area among species in both soils. With the exception of D. aromatica , species of the higher-nutrient soils had higher growth rates on both soils. 6 Although P addition led to elevated soil-P concentrations, elevated root-and leaf-tissue P concentrations on both soils, there was no significant growth enhancement and therefore no evidence that P availability limits the growth or constrains the distribution of any of the six species in the field. Differences in soil water availability between soils may be more important. 7 Our results suggest that habitat-mediated differences in seedling performance strongly influence the spatial distributions of tropical trees and are therefore likely to play a key role in structuring tropical rain forest communities
Phase Evolution and Li Diffusion in LATP Solid-State Electrolyte Synthesized via a Direct Heat-Cycling Method
Herein, the direct synthesis of phase-pure lithium aluminum titanium phosphate (Li_{1.3}Al_{0.3}Ti_{1.7}(PO_{4})_{3}, LATP) solid-electrolyte powder in 220 min and relatively low temperatures (850 °C) is achieved via a new (cyclic) fast heat treatment (c-FHT) route. The complex structural evolution highlights rate-limited lithium incorporation of intermediate metal phosphates formed prior to the final phase-pure LATP. The prepared LATP product powder displays similar bulk (2 × 10^{−10} cm^{2} s^{−1}) and local (3 × 10^{−10} cm^{2} s^{−1}) values for lithium diffusion coefficients (D_{Li}) characterized by electrochemical impedance spectroscopy and muon spin relaxation (μSR), respectively. The similarity between both D_{Li} values suggests excellent retention of inter- and intraparticle lithium diffusion, which is attributed to the absence of deleterious surface impurities such as AlPO4. A low-energy barrier (E_{a} = 73 meV) of lithium diffusion is also estimated from the μSR data
Rapid Quantification of Molecular Diversity for Selective Database Acquisition
There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities
Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.
Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion
Species-Area and Species-Individual Relationships for Tropical Trees: A Comparison of Three 50-ha Plots
Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study
Background Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi.
Methods We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies. In addition, blood cultures were taken from eligible patients presenting at Queen Elizabeth Central Hospital, Blantyre, as part of routine diagnosis. Inclusion criteria were measured or reported fever, or clinical suspicion of sepsis. Microbiologically, we identified Salmonella enterica serotype Typhi (S Typhi) isolates with a ciprofloxacin non-susceptible phenotype from blood cultures, and used whole-genome sequencing to identify drug-resistance mutations and phylogenetic relationships. We constructed generalised linear regression models to investigate associations between the number of ciprofloxacin prescriptions given per month to study participants and the proportion of S Typhi isolates with quinolone resistance-determining region (QRDR) mutations in the following month.
Findings From 46 989 blood cultures from Queen Elizabeth Central Hospital, 502 S Typhi isolates were obtained, 30 (6%) of which had either decreased ciprofloxacin susceptibility, or ciprofloxacin resistance. From 11 295 blood cultures from STRATAA and TyVAC studies, 241 microbiologically confirmed cases of typhoid fever were identified, and 198 isolates from 195 participants sequenced (mean age 12·8 years [SD 10·2], 53% female, 47% male). Between Oct 1, 2016, and Aug 31, 2019, of 177 typhoid fever cases confirmed by whole-genome sequencing, four (2%) were caused by S Typhi with QRDR mutations, compared with six (33%) of 18 cases between Sept 1 and Oct 31, 2019. This increase was associated with a preceding spike in ciprofloxacin prescriptions. Every additional prescription of ciprofloxacin given to study participants in the preceding month was associated with a 4·2% increase (95% CI 1·8–7·0) in the relative risk of isolating S Typhi with a QRDR mutation (p=0·0008). Phylogenetic analysis showed that S Typhi isolates with QRDR mutations from September and October, 2019, belonged to two distinct subclades encoding two different QRDR mutations, and were closely related (4–10 single-nucleotide polymorphisms) to susceptible S Typhi endemic to Blantyre.
Interpretation We postulate a causal relationship between increased ciprofloxacin prescriptions and an increase in fluoroquinolone non-susceptibility in S Typhi. Decreasing ciprofloxacin use by improving typhoid diagnostics, and reducing typhoid fever cases through the use of an efficacious vaccine, could help to limit the emergence of resistance.
Funding Wellcome Trust, Bill & Melinda Gates Foundation, and National Institute for Health and Care Research (UK)
Comprehensive genetic assessment of the ESR1 locus identifies a risk region for endometrial cancer
Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86x10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76x10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types
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