•Feeding camelina oil for 16 weeks does not impact health parameters in horses.•Blood parameters and BW are similar for horses fed camelina, flax, and canola oil.•Feeding camelina or flax oil ...decreases the n-6:n-3 ratio in equine plasma.•Plasma total lipid profile reflects the fatty acid profile of the oil provided.•Camelina oil can be used as a sustainable, alternative oil supplement for horses.
Camelina (Camelina sativa) is a hardy, low-input oilseed crop that provides a rich source of the n-3 fatty acid, α-linolenic acid (ALA). The primary purpose of the present study was to assess the effects of dietary camelina oil (CAM) consumption on various health parameters, as compared to horses fed canola oil (OLA) or flax oil (FLX). Secondly, to determine how dietary CAM, FLX, and OLA alter circulating plasma total lipids across time. Thirty horses, from three separate herds, were used for this study 14.9 years ± 5.3 years; 544 ± 66 kg calculated BW (mean ± SD). After a 4-week gradual acclimation period using sunflower oil mixed with soaked hay cubes, horses were balanced by location, age, sex, weight, and breed and randomly allocated to one of three treatment oils (CAM, OLA, or FLX) at an inclusion of 370 mg of oil/kg BW/day. Horses had ad libitum access to hay and/or pasture for the duration of the study. Body condition score (BCS), BW, oil intake, complete blood counts, plasma biochemical profiles, and plasma total lipids were measured on weeks 0, 2, 4, 8, and 16 throughout the 16-week treatment period. BW, BCS, and oil intake were analyzed using an ANOVA using PROC GLIMMIX in SAS Studio. Complete blood counts and biochemical profiles were analyzed using an ANCOVA, and fatty acids were analyzed using an ANOVA in PROC MIXED in SAS Studio. No differences were observed among treatment groups for BW, BCS, oil intake, complete blood counts, and biochemical parameters. Individual fatty acids that differed among treatments and/or across time were largely reflective of the different FA profiles of the oils provided. Most notably, plasma ALA was greater for FLX than OLA, but neither differed from CAM (P = 0.01). Linoleic acid did not differ among treatments or over time (P > 0.05). The n-6:n-3 ratio decreased over time for both CAM and FLX, and ratios were lower for FLX than OLA at week 16, but not different from CAM (P = 0.02). These results suggest that dietary CAM had no adverse effects on health parameters and that daily supplementation of CAM and FLX at 370 mg of oil/kg BW/day induces positive changes (a decrease) in the n-6:n-3 status of the horse. Consequently, CAM may be considered as an alternative oil to FLX in equine diets.
Australian law schools are becoming increasingly diverse. Yet, there is very little quantitative or qualitative data on diversity in law schools and even less research examining how students' diverse ...backgrounds and social identities - including their sexual orientation and gender identity - affect their law student experience. This article begins to fill this gap in the literature by reporting the findings from a study examining the law school experiences of LGBTQI+ students at all law schools within a single Australian state. The study reveals that much of the law school experience is similar for both LGBTQI+ and non-LGBTQI+ students, and that LGBTQI+ law students generally perceive law school to be an accepting and equitable environment. However, compared to their non-LGBTQI+ peers, LGBTQI+ law students self-censor more often, witness more bullying and harassment, and feel more stress when interacting with academic staff. Based on the findings from the study, the article suggests strategies law schools might consider to support LGBTQI+ diversity, visibly promote acceptance of "otherness" in tangible ways, and ensure a safe learning environment in which all students can flourish.
A detailed analysis of the promoter sequence requirements for the cAMP induction of transcription of the gene for phosphoenolpyruvate
carboxykinase (GTP) (EC 4.1.1.32) was undertaken. It was ...determined that the cAMP-responsive unit of this promoter consisted
of two independently weak or inactive components; the typical cAMP response element (CRE) sequence located at position -85
and a region of the promoter extending from -300 to -230 which contained multiple binding sites for liver-enriched nuclear
proteins. A previous study had indicated that multiple binding sites are critical for the activity of this latter region (Liu,
J., Park, E. A., Gurney, A. L., Roesler, W. J., and Hanson, R. W. (1991) J. Biol. Chem. 266, 19095-19102). In the present
study, we extend this observation by demonstrating that the activity of this region can be effectively substituted for by
three copies of just one subsite present in that region. This would suggest that the binding of three molecules of a single
liver-enriched factor is what forms this component of the cAMP response unit. The other component of the cAMP response unit,
the CRE, has been shown previously to be bound by these same liver-enriched factors as well as by cAMP response element binding
protein, leading to some debate as to the identity of the protein mediating the cAMP response through this element. By two
different experimental approaches, we show that neither CCAAT/enhancer binding protein nor D-site binding protein is the likely
mediator of the cAMP response through the CRE, while cAMP response element binding protein is a possible candidate.
Unacceptably dark bran color has prevented the white-kernelled variety Argent from meeting grain color marketing standards for hard white wheats (Triticum aestivum L.). The objective of this research ...was to identify phenolic compounds that negatively affect bran color in white wheat using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and vanillin-HCl and NaOH staining methods. In mature bran, FT-ICR-MS detected derivatives of the flavonol quercetin in varieties Argent and RL4137 (red-kernelled wheat) but not in W98616, a white wheat variety with acceptable grain color. Derivatives of the isoflavone formononetin were more abundant in W98616 relative to RL4137 and Argent. Vanillin-HCl staining indicated that RL4137 sequestered high levels of proanthocyanidin (PA) throughout its entire seed coat, whereas white wheats sequestered PAs as discrete speckles. Argent possessed abundant speckles over its entire seed coat, whereas speckles were almost undetectable in W98616. In mature kernels, flavonoids throughout the seed coat of RL4137 reacted with NaOH, but only the speckles appeared to react in white wheats. W98616 consistently had lighter grain than Argent before and after NaOH treatment. Free and bound phenolic differences in bran samples confirmed that the darker seed coat color of Argent, relative to W98616, was likely due to higher total phenolic acid content. Although isoflavones accumulated in Argent and RL4137, it appears that the majority of the flux through the flavonoid pathway ultimately accumulates quercetin derivatives and PAs. In W98616, PAs accumulate, but it appears that flavonoid biosynthesis ultimately accumulates isoflavones. Argent, compared to W98616, generally accumulated higher levels of total phenolics (flavonols, stilbenes, and PAs) within its darker pigmented bran.
Understanding animal terrestrialization, the process through which animals colonized the land, is crucial to clarify extant biodiversity and biological adaptation. Arthropoda (insects, spiders, ...centipedes and their allies) represent the largest majority of terrestrial biodiversity. Here we implemented a molecular palaeobiological approach, merging molecular and fossil evidence, to elucidate the deepest history of the terrestrial arthropods. We focused on the three independent, Palaeozoic arthropod terrestrialization events (those of Myriapoda, Hexapoda and Arachnida) and showed that a marine route to the colonization of land is the most likely scenario. Molecular clock analyses confirmed an origin for the three terrestrial lineages bracketed between the Cambrian and the Silurian. While molecular divergence times for Arachnida are consistent with the fossil record, Myriapoda are inferred to have colonized land earlier, substantially predating trace or body fossil evidence. An estimated origin of myriapods by the Early Cambrian precedes the appearance of embryophytes and perhaps even terrestrial fungi, raising the possibility that terrestrialization had independent origins in crown-group myriapod lineages, consistent with morphological arguments for convergence in tracheal systems.
This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Understanding the temporal context of terrestrialization in chelicerates depends on whether terrestrial groups, the traditional Arachnida, have a single origin and whether or not horseshoe crabs are ...primitively or secondarily marine. Molecular dating on a phylogenomic tree that recovers arachnid monophyly, constrained by 27 rigorously vetted fossil calibrations, estimates that Arachnida originated during the Cambrian or Ordovician. After the common ancestor colonized the land, the main lineages appear to have rapidly radiated in the Cambrian-Ordovician boundary interval, coinciding with high rates of molecular evolution. The highest rates of arachnid diversification are detected between the Permian and Early Cretaceous. A pattern of ancient divergence estimates for terrestrial arthropod groups in the Cambrian while the oldest fossils are Silurian (seen in both myriapods and arachnids) is mirrored in the molecular and fossil records of land plants. We suggest the discrepancy between molecular and fossil evidence for terrestrialization is likely driven by the extreme sparseness of terrestrial sediments in the rock record before the late Silurian.
The majority of extant arachnids are terrestrial, but other chelicerates are generally aquatic, including horseshoe crabs, sea spiders, and the extinct eurypterids. It is necessary to determine ...whether arachnids are exclusively descended from a single common ancestor (monophyly), because only that relationship is compatible with one land colonisation in chelicerate evolutionary history. Some studies have cast doubt on arachnid monophyly and recast the origins of their terrestrialization. These include some phylogenomic analyses placing horseshoe crabs within Arachnida, and from aquatic Palaeozoic stem-group scorpions. Here, we evaluate the possibility of arachnid monophyly by considering morphology, fossils and molecules holistically. We argue arachnid monophyly obviates the need to posit reacquisition/retention of aquatic characters such as gnathobasic feeding and book gills without trabeculae from terrestrial ancestors in horseshoe crabs, and that the scorpion total-group contains few aquatic taxa. We built a matrix composed of 200 slowly-evolving genes and re-analysed two published molecular datasets. We retrieved arachnid monophyly where other studies did not - highlighting the difficulty of resolving chelicerate relationships from current molecular data. As such, we consider arachnid monophyly the best-supported hypothesis. Finally, we inferred that arachnids terrestrialized during the Cambrian–Ordovician using the slow-evolving molecular matrix, in agreement with recent analyses.
•Arachnids are ancestrally terrestrial or amphibious, and probably lacked gnathobasic feeding, compound eyes and book gills.•It is unlikely that scorpions originated in aquatic environments.•A highly complete molecular matrix of 200 slowly evolving genes with diverse taxon sampling yields Arachnida without model-dependency.•Arachnids colonised land and diversified in the Cambrian–Ordovician.
Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumor-cell-intrinsic and microenvironmental features underpinning CPI ...sensitization. Here, we collated whole-exome and transcriptomic data for >1,000 CPI-treated patients across seven tumor types, utilizing standardized bioinformatics workflows and clinical outcome criteria to validate multivariable predictors of CPI sensitization. Clonal tumor mutation burden (TMB) was the strongest predictor of CPI response, followed by total TMB and CXCL9 expression. Subclonal TMB, somatic copy alteration burden, and histocompatibility leukocyte antigen (HLA) evolutionary divergence failed to attain pan-cancer significance. Dinucleotide variants were identified as a source of immunogenic epitopes associated with radical amino acid substitutions and enhanced peptide hydrophobicity/immunogenicity. Copy-number analysis revealed two additional determinants of CPI outcome supported by prior functional evidence: 9q34 (TRAF2) loss associated with response and CCND1 amplification associated with resistance. Finally, single-cell RNA sequencing (RNA-seq) of clonal neoantigen-reactive CD8 tumor-infiltrating lymphocytes (TILs), combined with bulk RNA-seq analysis of CPI-responding tumors, identified CCR5 and CXCL13 as T-cell-intrinsic markers of CPI sensitivity.
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•Large-scale meta-analysis of >1,000 CPI-treated cases with exome/transcriptome data•Clonal TMB and CXCL9/CXCL13 expression are the strongest predictors of CPI response•A multivariable predictor of CPI response significantly outperforms TMB•9q34 loss and CCND1 amplification are additional determinants of CPI response
A whole-exome and transcriptome meta-analysis of over 1,000 patients treated with immune checkpoint blockade across seven tumor types highlights the potential of multivariable prediction models that consider both tumor- and T-cell-intrinsic mechanisms of response.
Abstract
BACKGROUND
PSMA is a cell-surface protein that is highly expressed in the endothelium of the tumour neovasculature of several solid tumours, including glioblastoma (GBM), making it an ...excellent target for antibody-drug conjugates or peptide receptor radionuclide therapy. Several 68GaGa-PSMA-based radioligands have shown utility in the diagnosis and treatment response assessment of primary GBM patients in a number of case studies. The small-molecule ligand 68GaGa-PSMA-617 has the advantage of being suitable for radiolabelling with different radioisotopes, including 68Ga, 177Lu, 111In and 90Y, which raised the possibility of using it in a theranostic application in glioblastoma. The aim of this phase I/II prospective study was to evaluate the potential of 68GaGa-PSMA-617 as a PET imaging biomarker and as a candidate ligand for targeted radionuclide therapy in patients with recurrent GBM.
MATERIAL AND METHODS
Ten patients with recurrent glioblastoma were recruited for the study between October 2018 and September 2021. Patients underwent 68GaGa-PSMA-617 and 18FF-FET PET brain scans done on two separate days. Two patients had full-body 68GaGa-PSMA-617 scans. Tumour selectivity of 68GaGa-PSMA-617 was assessed by measuring tumour volume on 68GaGa-PSMA-617 PET scans and comparing it with tumour volume measured on 18FF-FET PET scans, which are more widely used clinically. Tumour specificity of 68GaGa-PSMA-617 was assessed by comparing its standard uptake value (SUV) and tumour-to-brain-ratio (TBR) with those of 18FF-FET TBR, and by measuring 68GaGa-PSMA-617 tumour-to-liver ratio (TLR).
RESULTS
PSMA-defined tumour volume was on average 1.87±1.10 times larger than the FET-defined tumour volume (p=0.084), and the two volumes had a DICE similarity coefficient of 0.578±0.175. Mean and maximum TBR was significantly (p=0.002) higher (~10x) for PSMA than for FET. Mean SUV in the tumour was significantly higher for FET than for PSMA (p=0.002), while maximum SUV was slightly higher for PSMA than for FET (p=0.08). For the two patients with full-body 68GaGa-PSMA PET scan available, PSMA mean TLR was 0.91 and 0.68, and maximum TLR was 1.20 and 1.07, respectively.
CONCLUSION
68Ga Ga-PSMA PET delineates a larger tumour volumes compared to 18FF-FET PET, suggesting there are areas of the tumour with emerging tumour neovasculature that are not yet metabolically active. The poor spatial overlap between PSMA and FET tumour volume suggests the complementary diagnostic role of the two tracers. The higher TBR of PSMA compared to FET demonstrates the higher tumour specificity of the former, and thus its potential ability as a diagnostic agent for recurrent tumour volume delineation. Relatively low values of PSMA SUV and TLR suggest that PSMA specific uptake is not sufficient to use this ligand for targeted radionuclide therapy in glioblastoma when conjugated to 177Lu.
Gaza War: Too many citizens being killed Yaqub, Sheraz; Edwin, Bjørn; Hammoud, Zane ...
British journal of surgery,
04/2024, Letnik:
111, Številka:
4
Journal Article
PDF
