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Duncan, A.

Publications and source records attributed to Duncan, A..

18 recordsLinked to original sources

Protal: Ultra-fast metagenomic profiling and strain-resolved analysis

Large-scale metagenomic studies increasingly require taxonomic profiles that are sensitive, precise, strain-resolved and computationally tractable. Existing profilers typically trade taxonomic breadth, sensitivity, precision and speed against one another, limiting their utility for high-resolution microbiome analyses. Here we present protal -- profiling through alignment -- an ultra-fast alignment-based method for species-and strain-resolved profiling of metagenomes. Protal combines a newly developed alignment algorithm, machine-learning-based classification and conserved bacterial marker genes to profile species represented in the standardized and regularly updated GTDB taxonomy. Protal reliably profiles all 143,614 bacterial and archaeal species in GTDB r226 and achieved higher precision on CAMI2 benchmarks than all tested contemporary profilers, including MetaPhlAn 4, mOTUs4, sylph and Kraken2+Bracken (mean species-level precision 98.3% versus 97.5% for the next-best profiler, sylph). In custom benchmarks, protal showed particularly strong gains for rare species represented by a single reference genome and for highly complex communities containing 10,000 species (F1-score 9% and 14% higher than the second best profiler, respectively). At the strain level, protal reconstructs intraspecific phylogenetic relationships among detected bacteria with similar accuracy as StrainPhlAn 4; because protal produces precise alignments, the phylogenies can be de novo produced without reliance on reference strain collections. Unlike dedicated strain-profiling workflows, however, protal performs strain analysis concurrently with species-level profiling, making it up to 40-fold faster without requiring additional steps. Together, these features make strain-resolved profiling of thousands of metagenomes feasible on commodity hardware. The software, databases and tutorials are available at https://github.com/4less/protal and http://protal.earlham.ac.uk.

bioinformatics↗

Preclinical efficacy and safety of Tegavivint in Wnt-activated hepatocellular carcinoma

Background & AimsHepatocellular carcinoma (HCC), a predominant form of liver cancer, remains a significant clinical unmet need. Given that 30-50% of HCC cases harbour mutations in the Wnt/{beta}-catenin signalling pathway, targeting this cascade represents a promising therapeutic strategy. However, the clinical translation of Wnt inhibitors has been hindered by severe adverse events observed in preclinical models and early-phase clinical trials, primarily due to the essential role of Wnt signalling in maintaining normal tissues such as the intestine and bone. MethodsWe examined the efficacy of Tegavivint, a first-in-class Wnt pathway inhibitor that targets TBL1, against HCC to elucidate its underlying mechanism of action. We evaluated the dose-response of Tegavivint and its effects on the cell cycle, apoptosis, and Wnt target gene expression using HepG2, HUH6, and HUH7 cell lines in vitro. Furthermore, we employed an orthotopic xenograft transplant model using HepG2 cells in immunodeficient mice to assess the safety profile and on-target anti-cancer efficacy of Tegavivint in vivo. ResultsTegavivint exhibited potent Wnt pathway-suppressing effects in cancer cells with constitutive Wnt pathway activation. Notably, Tegavivint displayed robust anti-tumour activity across a broad range of HCC cell lines, regardless of their Wnt pathway activation status. While Tegavivint inhibited the Wnt pathway and triggered the activation of apoptotic pathways in most cell lines, our findings suggest that it also can induce cell death by activating alternative non-apoptotic pathways in apoptosis-resistant cancer cells. In an orthotopic transplant mouse model, Tegavivint significantly downregulated Wnt pathway target genes, inhibited cell proliferation, induced apoptosis and suppressed growth in tumours. ConclusionsTaken together, our data establish a robust foundation for evaluating Tegavivint as a novel therapeutic option, specifically tailored for HCC patients harbouring Wnt-driven hepatic malignancies.

cancer biology↗

A chronic state biostimuli-responsive therapeutic model system: applications to skin tissue repair and regeneration

We report on the elaboration of a biocompatible therapeutic model system (TMS) capable of detecting the state of chronicity of a wound and responding to the latter by releasing the appropriate healing agent (antibiotic but not only). Different formulations of PVA-borate hydrogel systems containing methylene blue (MB) and levofloxacin (L) drug antibiotic were prepared. We were able to demonstrate sensitivity to microenvironmental factors such as pH, and high levels of ROS - a major biomarker of a chronic inflammation state. Furthermore, these reversible gels "open" and enact an ROS triggered drug delivery response. These results are promising in that they provide a potent wound dressing layer capable of sensing the chronic state of a wound and responding conditionally to the latter by delivering the appropriate amount of drug only when required. Furthermore, our system may be optimized for chronic wound dressing healing and promote better wound care by limiting unnecessary overexposure of the patient to the antibiotic. Our system provides a potent novel tool to the arsenal of existing strategies aiming at combatting bacterial resistance to antibiotics - a global societal challenge. Our results additionally confirmed good biocompatibility for skin tissue regeneration.

systems biology↗

Optimizing storage, high-molecular weight DNA extraction and genome reconstructions from human faecal samples.

Metagenomic sequencing has become an essential tool for assessing the composition and functional potential of microbial communities. However, established metagenomic DNA extraction protocols are limited by trade-offs between universal taxonomic representation, DNA quality, quantity and molecule length, making them mostly unsuitable for 3rd generation sequencing. MethodsWe assessed the effectiveness of high molecular weight (HMW) DNA workflows from faecal samples, using different combinations of collection, storage and extraction kits. Faecal samples were either immediately processed, frozen at -80{degrees}C or stored in DNA/RNA Shield, GutAlive or OMNIgeneGUT and then subjected to three different DNA isolation kits, each modified for mechanical, chemical and enzymatic cell lysis steps, totalling 32 evaluated combinations. Isolated DNA was assessed for its quality and quantity, while taxonomic consistency was evaluated using metataxonomics and validated with metagenomic sequencing. ResultsThe yield of HMW DNA differed substantially between storage and DNA extraction protocols. Specifically, storage protocol had the highest impact on HMW DNA recovery, with DNA/RNA Shield storage yielding on average 51% more HMW DNA >30kb. Similarly, the sample storage had independently the effect size of R2 = 26.9% on the microbiome composition, and since the DNA extraction protocol in our study inherently combines both DNA extraction kit and lysis type, the latter had the largest effect size (R2 = 12.8%). While all kits had specific dis/advantages and biases, DNA/RNA Shield and Maxwell RSC PureFood GMO and Authentication kit performed best overall for long-read metagenomics. The protocol was validated on a) isolate genomes and b) 4 faecal samples, demonstrating both increased DNA yield at >30kb molecule length. Using the MG-TK pipeline these metagenomes yielded genomes on average, per sample, 48 Pacific Biosciences (PacBio) and 55 Oxford Nanopore Technologies (ONT) circular bacterial metagenomic assembled genomes. ConclusionThe current gold-standard of freezing faecal samples was surprisingly inconsistent and inefficient for long-read metagenomics, necessitating rethinking gut microbial study designs. We provide a simple and cheap protocol that preserves both taxonomic composition and HMW DNA quality, while our bioinformatics workflow allows for complete bacterial genome reconstruction.

molecular biology↗

N'-(1-phenylethylidene)-benzohydrazide cytotoxicity is LSD1 independent and linked to Fe-S cluster disruption in Ewing sarcoma

The noncompetitive LSD1 inhibitors SP-2509 and SP-2577 are N-(1-phenylethylidene)-benzohydrazides that display potent activity in Ewing sarcoma. They block transcriptional regulation of the causative oncogenic fusion protein, EWSR1::FLI1, and cause cell death. However, SP-2509 and SP-2577 are the only LSD1 inhibitors active in Ewing sarcoma; other LSD1 inhibitors have little effect. Studies from our group and others suggest SP-2509 activity may result from off-target activity affecting the mitochondria. Here we identified potential off-target mechanisms of N-(1-phenylethylidene)-benzohydrazides using an unbiased approach, cellular thermal shift assay coupled to mass spectrometry (CETSA-MS). Interestingly, this revealed significant destabilization of the electron transport chain complex III protein ubiquinol-cytochrome c reductase (UQCRFS1). We find that UQCRFS1 destabilization is likely linked to impaired iron-sulfur (Fe-S) cofactor binding, and that SP-2509 broadly destabilizes cellular Fe-S proteins. Using both chemical and genetic tools, we show that SP-2509 mediated cell death is LSD1 independent and instead requires a N-(2-hydroxybenzylidene)hydrazide. Our studies suggest this core moiety alters iron metabolism in the cell. Importantly, we also find that the reversal of EWSR1::FLI1 transcriptional regulation by SP-2509 is independent from LSD1 inhibition. This unique activity is instead associated with the N-(2-hydroxybenzylidene)-hydrazide core and destabilization of Fe-S proteins. These findings reveal a novel mechanism of action for this class of compounds and raise additional questions regarding how EWSR1::FLI1 transcriptional regulation is linked to Fe-S biogenesis, the precise mechanisms of cell death, the biological features of susceptible cancer cells, and strategies for clinical translation.

pharmacology and toxicology↗

One year of gluten free diet impacts gut function and microbiome in celiac disease

BACKGROUND & AIMSCurrently, the main treatment option for coeliac disease (CD) is a gluten free diet (GFD). This observational cohort study investigated the impact of CD and 1 year of GFD on gut function and microbiome. METHODS36 newly diagnosed patients and 36 healthy volunteers (HV) were studied at baseline and at 12 months follow up. Small bowel water content (SBWC), whole gut transit time (WGTT) and colon volumes were measured by MRI. Stool samples DNA was subjected to shotgun metagenomic sequencing. Species level abundances and gene functions, including carbohydrate active enzymes (CAZymes) were determined. RESULTSSBWC was significantly higher in people with CD 157{+/-}15 mL versus HVs 100{+/-}12 mL (p=0.003). WGTT was delayed in people with CD 68{+/-}8 hours versus HVs 41{+/-}5 hours (p=0.002). The differences reduced after 12 months of GFD but not significantly. Wellbeing in the CD group significantly improved after GFD but did not recover to control values. CD faecal microbiota showed high abundance of proteolytic gene functions, associated with Escherichia coli, Enterobacter and Peptostreptococcus. GFD significantly reduced Bifidobacteria and increased Blautia wexerelae. Microbiome composition correlated positively with WGTT, colonic volume and Akkermansia municphilia but negatively with B.wexerelae. Following GFD the reduction in WGTT and colonic volume significantly associated with increased abundance of B.wexerelae. There were also significant alterations in CAZyme profiles, specifically starch and arabinoxylan degrading families. CONCLUSIONSCD impacted gut function and microbiota. GFD ameliorated but did not reverse these effects, significantly reducing Bifidobacteria associated with reduced intake of resistant starch and arabinoxylan from wheat.

physiology↗

Seclidemstat blocks the transcriptional function of multiple FET-fusion oncoproteins

Genes encoding the RNA-binding proteins FUS, EWSR1, and TAF15 (FET proteins) are involved in chromosomal translocations in rare sarcomas. FET-rearranged sarcomas are often aggressive malignancies affecting patients of all ages. New therapies are needed. These translocations fuse the 5 portion of the FET gene with a 3 partner gene encoding a transcription factor (TF). The resulting fusion proteins are oncogenic TFs with a FET protein low complexity domain (LCD) and a DNA binding domain. FET fusion proteins have proven stubbornly difficult to target directly and promising strategies target critical co-regulators. One candidate is lysine specific demethylase 1 (LSD1). LSD1 is recruited by multiple FET fusions, including EWSR1::FLI1. LSD1 promotes EWSR1::FLI1 activity and treatment with the noncompetitive inhibitor SP-2509 blocks EWSR1::FLI1 transcriptional function. A similar molecule, seclidemstat (SP-2577), is currently in clinical trials for FET-rearranged sarcomas (NCT03600649). However, whether seclidemstat has pharmacological activity against FET fusions has not been demonstrated. Here, we evaluate the in vitro potency of seclidemstat against multiple FET-rearranged sarcoma cell lines, including Ewing sarcoma, desmoplastic small round cell tumor, clear cell sarcoma, and myxoid liposarcoma. We also define the transcriptomic effects of seclidemstat treatment and evaluated the activity of seclidemstat against FET fusion transcriptional regulation. Seclidemstat showed potent activity in cell viability assays across FET-rearranged sarcomas and disrupted the transcriptional function of all tested fusions. Though epigenetic and targeted inhibitors are unlikely to be effective as a single agents in the clinic, these data suggest seclidemstat remains a promising new treatment strategy for patients with FET-rearranged sarcomas. SIGNIFICANCEHere, we show the noncompetitive inhibitor, seclidemstat, has in vitro activity against multiple FET fusion proteins that cause a number of rare and aggressive sarcomas. These data represent one of the largest analyses of FET fusion activity across multiple malignancies and are a valuable resource for those studying FET-rearranged sarcomas.

cancer biology↗

JBrowse 2: A modular genome browser with views of synteny and structural variation

We present JBrowse 2, a general-purpose genome annotation browser offering enhanced visualization of complex structural variation and evolutionary relationships. JBrowse 2 retains the core features of the open-source JavaScript genome browser JBrowse while adding new views for synteny, dotplots, breakpoints, gene fusions, and whole-genome overviews. The software readily allows users to share sessions, open multiple genomes or views, and navigate quickly between these views. It can be embedded in a web page, used as a standalone desktop application, or run from Jupyter notebooks or R sessions. Using a plugin framework, developers can create new data adapters, track types, and visualizations. These improvements are enabled by a ground-up redesign of the JBrowse architecture using modern web technology. We describe application functionality, use cases, performance benchmarks, and implementation notes for web administrators and developers.

bioinformatics↗

On-farm Implementation of Midseason Drainage to Decrease Greenhouse Gas Emissions and Grain Arsenic Concentration in Rice Systems

Rice (Oryza sativa L.) is an important staple crop throughout much of the world, however, it is also a significant source of agricultural methane (CH4) emissions and exposure to arsenic (As). Introduction of soil aerobic events through practices such as alternate wetting and drying or midseason drainage, in flooded rice systems can significantly decrease grain As concentration and seasonal CH4 emissions. Previous on small research plots research has shown that a single midseason drain accomplishes these goals without yield reduction, but the degree of benefit depends on soil-drying severity. A midseason drain also has the potential to fit in well within current management practices of California rice systems, however, it has not been tested across a wide range of soil types or at a scale that farmers typically manage in this region. Therefore, in this three-year study, we aimed to determine if the results from previous small plot research are similar to what can be expected on-farm. At seven on-farm trials we implemented a single midseason drain and compared the grain yields, GHG emissions, and As concentration to the traditional farmer practice (FP) practiced in an adjacent part of the field. Soil moisture parameters [perched water table, volumetric water content, gravimetric water content (GWC), and soil water potential], CH4 and nitrous oxide (N2O) emissions, grain As and cadmium concentration, and grain yield were quantified. Across site-years, midseason drainage reduced seasonal CH4 emissions by 20-77%, compared to the FP control with the magnitude of reduction related to the soil-drying severity. For every 1% reduction in soil GWC during the drainage period, CH4 emissions were reduced by approximately 3.2%, compared to 2.5% in previous on-station research using small plots. Midseason drainage increased N2O emissions (average = 0.248 kg N2O-N ha-1) compared to the control but this accounted for only 3% of the seasonal global warming potential across all drainage treatments. Drainage also decreased grain As concentration by approximately 20%, on average, but was not related to the degree of soil-drying. Importantly, midseason drainage had no significant impact on grain yields. Overall, these results confirm findings from previous on-station research, indicating that midseason drainage may be a viable on-farm management practice for GHG mitigation and for reducing grain As concentration in flooded rice fields with limited risk of yield reduction.

ecology↗

PyLipID: A Python package for analysis of protein-lipid interactions from MD simulations

Lipids play important modulatory and structural roles for membrane proteins. Molecular dynamics simulations are frequently used to provide insights into the nature of these proteinlipid interactions. Systematic comparative analysis requires tools that provide algorithms for objective assessment of such interactions. We introduce PyLipID, a python package for the identification and characterization of specific lipid interactions and binding sites on membrane proteins from molecular dynamics simulations. PyLipID uses a community analysis approach for binding site detection, calculating lipid residence times for both the individual protein residues and the detected binding sites. To assist structural analysis, PyLipID produces representative bound lipid poses from simulation data, using a density-based scoring function. To estimate residue contacts robustly, PyLipID uses a dual-cutoff scheme to differentiate between lipid conformational rearrangements whilst bound from full dissociation events. In addition to the characterization of protein-lipid interactions, PyLipID is applicable to analysis of the interactions of membrane proteins with other ligands. By combining automated analysis, efficient algorithms, and open-source distribution, PyLipID facilitates the systematic analysis of lipid interactions from large simulation datasets of multiple species of membrane proteins. ToC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/452312v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1f6530corg.highwire.dtl.DTLVardef@c639d5org.highwire.dtl.DTLVardef@1fef967org.highwire.dtl.DTLVardef@a80446_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Identification and assessment of cardiolipin interactions with E. coli inner membrane proteins

Integral membrane proteins are localised and/or regulated by lipids present in the surrounding bilayer. Whilst bacteria such as E. coli have relatively simple membranes when compared to eukaryotic cells, there is ample evidence that many bacterial proteins bind to specific lipids, especially the anionic lipid cardiolipin. Here, we apply molecular dynamics simulations to assess lipid binding to 42 different E. coli inner membrane proteins. Our data reveals a strong asymmetry between the membrane leaflets, with a marked increase of anionic lipid binding to the inner leaflet regions of membrane proteins, particularly for cardiolipin. From our simulations we identify over 700 independent cardiolipin binding sites, allowing us to identify the molecular basis of a prototypical cardiolipin binding site, which we validate against structures of bacterial proteins bound to cardiolipin. This allows us to construct a set of metrics for defining a high affinity cardiolipin binding site on (bacterial) membrane proteins, paving the way for a heuristic approach to defining more complex protein-lipid interactions.

biochemistry↗

Myanmar's terrestrial ecosystems: status, threats and conservation opportunities

Myanmar is highly biodiverse, with more than 16,000 plant, 314 mammal, 1131 bird, 293 reptile, and 139 amphibian species. Supporting this biodiversity is a variety of natural ecosystems--mostly undescribed--including tropical and subtropical forests, savannas, seasonally inundated wetlands, extensive shoreline and tidal systems, and alpine ecosystems. Although Myanmar contains some of the largest intact natural ecosystems in Southeast Asia, remaining ecosystems are under threat from accelerating land use intensification and over-exploitation. In this period of rapid change, a systematic risk assessment is urgently needed to estimate the extent and magnitude of human impacts and identify ecosystems most at risk to help guide strategic conservation action. Here we provide the first comprehensive conservation assessment of Myanmars natural terrestrial ecosystems using the IUCN Red List of Ecosystems categories and criteria. We identified 64 ecosystem types for the assessment, and used models of ecosystem distributions and syntheses of existing data to estimate declines in distribution, range size, and functioning of each ecosystem. We found that more than a third (36.9%) of Myanmars area has been converted to anthropogenic ecosystems over the last 2-3 centuries, leaving nearly half of Myanmars ecosystems threatened (29 of 64 ecosystems). A quarter of Myanmars ecosystems were identified as Data Deficient, reflecting a paucity of studies and an urgency for future research. Our results show that, with nearly two-thirds of Myanmar still covered in natural ecosystems, there is a crucial opportunity to develop a comprehensive protected area network that sufficiently represents Myanmars terrestrial ecosystem diversity.

ecology↗

Metagenome-assembled genomes of phytoplankton communities across the Arctic Circle

Phytoplankton communities significantly contribute to global biogeochemical cycles of elements and underpin marine food webs. Although their uncultured genetic diversity has been estimated by planetary-scale metagenome sequencing and subsequent reconstruction of metagenome-assembled genomes (MAGs), this approach has yet to be applied for eukaryote-enriched polar and non-polar phytoplankton communities. Here, we have assembled draft prokaryotic and eukaryotic MAGs from environmental DNA extracted from chlorophyll a maximum layers in the surface ocean across the Arctic Circle in the Atlantic. From 679 Gbp and estimated 50 million genes in total, we recovered 140 MAGs of medium to high quality. Although there was a strict demarcation between polar and non-polar MAGs, adjacent sampling stations in each environment on either side of the Arctic Circle had MAGs in common. Furthermore, phylogenetic placement revealed eukaryotic MAGs to be more diverse in the Arctic whereas prokaryotic MAGs were more diverse in the Atlantic south of the Arctic Circle. Approximately 60% of protein families were shared between polar and non-polar MAGs for both prokaryotes and eukaryotes. However, eukaryotic MAGs had more protein families unique to the Arctic whereas prokaryotic MAGs had more families unique to south of the Arctic circle. Thus, our study enabled us to place differences in functional plankton diversity in a genomic context to reveal that the evolution of these MAGs likely was driven by significant differences in the seascape on either side of an ecosystem boundary that separates polar from non-polar surface ocean waters in the North Atlantic.

microbiology↗

Consequences of population structure for sex allocation and sexual conflict

Both sex allocation and sexual conflict can be modulated by spatial structure. However, how the interplay between the type of dispersal and the scale of competition simultaneously affects these traits in sub-divided populations is rarely considered. We investigated sex allocation and sexual conflict evolution in meta-populations of the spider mite Tetranychus urticae evolving under budding (pairing females from the same patch) or random (pairing females from different patches) dispersal and either local (fixed sampling from each subpopulation) versus global (sampling as a function of subpopulation productivity) competition. Females evolving under budding dispersal produced less female-biased offspring sex ratios than those from the random dispersal selection regimes, contradicting theoretical predictions. In turn, the scale of competition did not have a strong effect on sex allocation. Males evolved under budding dispersal induced less female harm than those exposed to random dispersal, but there was no reduction in female fitness following exposure to multiple mates from either selection regime. This work highlights that population structure can impact the evolution of sex allocation and sexual conflict. We also discuss how selection on either trait may reciprocally affect the evolution of the other, for example via effects on fecundity.

evolutionary biology↗

Only 40% of the world's forests are in good health

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remains poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate the first globally-consistent, continuous index of forest condition as determined by degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) have high landscape level integrity (mostly found in Canada, Russia, the Amazon, Central Africa and New Guinea) and only 27% of this area is found in nationally-designated protected areas. Of the forest in protected areas, only 56% has high landscape level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.

ecology↗

Effect of sampling frequency on fractal fluctuations during treadmill walking

The temporal dynamics of stride-to-stride fluctuations in steady-state walking reveal important information about locomotor control and can be quantified using so-called fractal analyses, notably the detrended fluctuation analysis (DFA). Gait dynamics are often collected during treadmill walking using 3-D motion capture to identify gait events from kinematic data. The sampling frequency of motion capture systems may impact the precision of event detection and consequently impact the quantification of stride-to-stride variability. This study aimed i) to determine if collecting multiple walking trials with different sampling frequency affects DFA values of spatiotemporal parameters during treadmill walking, and ii) to determine the reliability of DFA values across downsampled conditions. Seventeen healthy young adults walked on a treadmill while their gait dynamics was captured using different sampling frequency (60, 120 and 240 Hz) in each condition. We also compared data from the highest sampling frequency to downsampled versions of itself. We applied DFA to the following time series: step length, time and speed, and stride length, time and speed. Reliability between experimental conditions and between downsampled conditions were measured with 1) intraclass correlation estimates and their 95% confident intervals, calculated based on a single-measurement, absolute-agreement, two-way mixed-effects model (ICC 3,1), and 2) Bland-Altman bias and limits of agreement. Both analyses revealed a poor reliability of DFA results between conditions using different sampling frequencies, but a relatively good reliability between original and downsampled spatiotemporal variables. Collectively, our results suggest that using sampling frequencies of 120 Hz or 240 Hz provide similar results, but that using 60 Hz may alter DFA values. We recommend that gait kinematics should be collected at around 120 Hz, which provides a compromise between event detection accuracy and processing time.

bioengineering↗

The effect of dietary intervention on inflammatory markers in patients with type 2 diabetes. An analysis of the Lifestyle Over and Above Drugs in Diabetes (LOADD) study

Ninety-three participants with poorly controlled type 2 diabetes despite optimized drug therapy were randomised to receive intensive dietary advice or usual care for six months. Following dietary intervention a significant reduction in interleukin-18 levels was observed, with a ratio of change (95% CI) of 0.90 (0.82-0.99); p = 0.033. Changes in IL-18 correlated with changes in neopterin, r = 0.299 (p = 0.009)

clinical trials↗

Transgenerational cues about local mate competition affect offspring sex ratios in the spider mite Tetranychus urticae

In structured populations, competition for mates between closely related males, termed Local Mate Competition (LMC), is expected to select for female-biased offspring sex ratios. However, the cues underlying sex allocation decisions remain poorly studied. Here, we test for several cues in the spider mite Tetranychus urticae, a species that was previously found to adjust the sex ratio of its offspring in response to the number of females in an isolated population, i.e. a patch. We here investigate whether the offspring sex ratio of T. urticae females changes in response to 1) the current number of females in the same patch, 2) the number of females in the patches of their mothers and 3) their relatedness to their mate. Single females on patches produced similar sex ratios to those of groups of 15 females; their mothers had been in identical conditions of panmixia. The offspring sex ratios of females mated with their brother did not differ from those of females mated with an unrelated male. Females however produced a more female-biased offspring sex ratio if their mothers were alone on a patch compared to 15 other females. Thus, maternal environment is used as a cue for the sex allocation of daughters. We discuss the conditions under which the maternal environment may be a reliable predictor of LMC experienced by grand-sons.

evolutionary biology↗