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1.
Anal Chem ; 96(10): 4171-4179, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38358916

ABSTRACT

We present an integrated, open-source device for parahydrogen-based hyperpolarization processes in the microtesla field regime with a cost of components of less than $7000. The device is designed to produce a batch of 13C and 15N hyperpolarized (HP) compounds via hydrogenative or non-hydrogenative parahydrogen-induced polarization methods that employ microtesla magnetic fields for efficient polarization transfer of parahydrogen-derived spin order to X-nuclei (e.g., 13C and 15N). The apparatus employs a layered structure (reminiscent of a Russian doll "Matryoshka") that includes a nonmagnetic variable-temperature sample chamber, a microtesla magnetic field coil (operating in the range of 0.02-75 microtesla), a three-layered mu-metal shield (to attenuate the ambient magnetic field), and a magnetic shield degaussing coil placed in the overall device enclosure. The gas-handling manifold allows for parahydrogen-gas flow and pressure control (up to 9.2 bar of total parahydrogen pressure). The sample temperature can be varied either using a water bath or a PID-controlled heat exchanger in the range from -12 to 80 °C. This benchtop device measures 62 cm (length) × 47 cm (width) × 47 cm (height), weighs 30 kg, and requires only connections to a high-pressure parahydrogen gas supply and a single 110/220 VAC power source. The utility of the device has been demonstrated using an example of parahydrogen pairwise addition to form HP ethyl [1-13C]acetate (P13C = 7%, [c] = 1 M). Moreover, the Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) technique was employed to demonstrate efficient hyperpolarization of 13C and 15N spins in a wide range of biologically relevant molecules, including [1-13C]pyruvate (P13C = 14%, [c] = 27 mM), [1-13C]-α-ketoglutarate (P13C = 17%), [1-13C]ketoisocaproate (P13C = 18%), [15N3]metronidazole (P15N = 13%, [c] = 20 mM), and others. While the vast majority of the utility studies have been performed in standard 5 mm NMR tubes, the sample chamber of the device can accommodate a wide range of sample container sizes and geometries of up to 1 L sample volume. The device establishes an integrated, simple, inexpensive, and versatile equipment gateway needed to facilitate parahydrogen-based hyperpolarization experiments ranging from basic science to preclinical applications; indeed, detailed technical drawings and a bill of materials are provided to support the ready translation of this design to other laboratories.

2.
Molecules ; 29(2)2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38257401

ABSTRACT

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer's Disease (AD)-like pathology in mice, although the mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report an isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/18F]exchange reaction over IDIF in dimethyl sulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7 ± 3% radiochemical yield in a 20 min reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t > 10 min post administration), rapid accumulation in the liver, long circulation time, and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.


Subject(s)
Alzheimer Disease , Diflunisal/analogs & derivatives , Humans , Animals , Mice , Pharmaceutical Preparations , Tissue Distribution , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/drug therapy , Prealbumin , Amyloid beta-Peptides , Excipients
3.
Genetics ; 226(3)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38124392

ABSTRACT

Meiotic crossovers are initiated from programmed DNA double-strand breaks. The Msh4-Msh5 heterodimer is an evolutionarily conserved mismatch repair-related protein complex that promotes meiotic crossovers by stabilizing strand invasion intermediates and joint molecule structures such as Holliday junctions. In vivo studies using homozygous strains of the baker's yeast Saccharomyces cerevisiae (SK1) show that the Msh4-Msh5 complex associates with double-strand break hotspots, chromosome axes, and centromeres. Many organisms have heterozygous genomes that can affect the stability of strand invasion intermediates through heteroduplex rejection of mismatch-containing sequences. To examine Msh4-Msh5 function in a heterozygous context, we performed chromatin immunoprecipitation and sequencing (ChIP-seq) analysis in a rapidly sporulating hybrid S. cerevisiae strain (S288c-sp/YJM789, containing sporulation-enhancing QTLs from SK1), using SNP information to distinguish reads from homologous chromosomes. Overall, Msh5 localization in this hybrid strain was similar to that determined in the homozygous strain (SK1). However, relative Msh5 levels were reduced in regions of high heterozygosity, suggesting that high mismatch densities reduce levels of recombination intermediates to which Msh4-Msh5 binds. Msh5 peaks were also wider in the hybrid background compared to the homozygous strain (SK1). We determined regions containing heteroduplex DNA by detecting chimeric sequence reads with SNPs from both parents. Msh5-bound double-strand break hotspots overlap with regions that have chimeric DNA, consistent with Msh5 binding to heteroduplex-containing recombination intermediates.


Subject(s)
Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae , Chromosomes , Crossing Over, Genetic , DNA, Cruciform/metabolism , Meiosis/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism
4.
J Phys Chem A ; 127(23): 5018-5029, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37278605

ABSTRACT

Efficient 15N-hyperpolarization of [15N3]metronidazole was reported previously using the Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) technique. This hyperpolarized FDA-approved antibiotic is a potential contrast agent because it can be administered in a large dose and because previous studies revealed long-lasting HP states with exponential decay constant T1 values of up to 10 min. Possible hypoxia-sensing applications have been proposed using hyperpolarized [15N3]metronidazole. In this work, we report on the functionalization of [15N3]metronidazole with a fluorine-19 moiety via a one-step reaction to substitute the -OH group. SABRE-SHEATH hyperpolarization studies of fluoro-[15N3]metronidazole revealed efficient hyperpolarization of all three 15N sites with maximum %P15N values ranging from 4.2 to 6.2%, indicating efficient spin-relayed polarization transfer in microtesla fields via the network formed by 2J15N-15N. The corresponding 15N to 19F spin-relayed polarization transfer was found to be far less efficient with %P19F of 0.16%, i.e., more than an order of magnitude lower than that of 15N. Relaxation dynamics studies in microtesla fields support a spin-relayed polarization transfer mechanism because all 15N and 19F spins share the same T1 value of ca. 16-20 s and the same magnetic field profile for the SABRE-SHEATH polarization process. We envision the use of fluoro-[15N3]metronidazole as a potential hypoxia sensor. It is anticipated that under hypoxic conditions, the nitro group of fluoro-[15N3]metronidazole undergoes electronic stepwise reduction to an amino derivative. Ab initio calculations of 15N and 19F chemical shifts of fluoro-[15N3]metronidazole and its putative hypoxia-induced metabolites clearly indicate that the chemical shift dispersions of all three 15N sites and the 19F site are large enough to enable the envisioned hypoxia-sensing approaches.


Subject(s)
Fluorine , Metronidazole , Magnetic Resonance Spectroscopy/methods , Nitrogen Isotopes
5.
Plants (Basel) ; 12(12)2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37375992

ABSTRACT

Soil salinity can impose substantial stress on plant growth and cause significant yield losses. Crop varieties tolerant to salinity stress are needed to sustain yields in saline soils. This requires effective genotyping and phenotyping of germplasm pools to identify novel genes and QTL conferring salt tolerance that can be utilised in crop breeding schemes. We investigated a globally diverse collection of 580 wheat accessions for their growth response to salinity using automated digital phenotyping performed under controlled environmental conditions. The results show that digitally collected plant traits, including digital shoot growth rate and digital senescence rate, can be used as proxy traits for selecting salinity-tolerant accessions. A haplotype-based genome-wide association study was conducted using 58,502 linkage disequilibrium-based haplotype blocks derived from 883,300 genome-wide SNPs and identified 95 QTL for salinity tolerance component traits, of which 54 were novel and 41 overlapped with previously reported QTL. Gene ontology analysis identified a suite of candidate genes for salinity tolerance, some of which are already known to play a role in stress tolerance in other plant species. This study identified wheat accessions that utilise different tolerance mechanisms and which can be used in future studies to investigate the genetic and genic basis of salinity tolerance. Our results suggest salinity tolerance has not arisen from or been bred into accessions from specific regions or groups. Rather, they suggest salinity tolerance is widespread, with small-effect genetic variants contributing to different levels of tolerance in diverse, locally adapted germplasm.

6.
Angew Chem Int Ed Engl ; 62(31): e202219181, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37247411

ABSTRACT

We report dissolution Dynamic Nuclear Polarization (d-DNP) of [15 N3 ]metronidazole ([15 N3 ]MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a hypoxia-sensing molecular probe using 15 N hyperpolarized (HP) nucleus. The DNP process is very efficient for [15 N3 ]MNZ with an exponential build-up constant of 13.8 min using trityl radical. After dissolution and sample transfer to a nearby 4.7 T Magnetic Resonance Imaging scanner, HP [15 N3 ]MNZ lasted remarkably long with T1 values up to 343 s and 15 N polarizations up to 6.4 %. A time series of HP [15 N3 ]MNZ images was acquired in vitro using a steady state free precession sequence on the 15 NO2 peak. The signal lasted over 13 min with notably long T2 of 20.5 s. HP [15 N3 ]MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP 15 N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.


Subject(s)
Anti-Bacterial Agents , Metronidazole , Rats , Animals , Metronidazole/pharmacology , Anti-Bacterial Agents/pharmacology , Solubility , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Imaging
7.
Data Brief ; 46: 108787, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36506801

ABSTRACT

This article describes a dataset of high-resolution visible-spectrum images of safflower (Carthamus tinctorius L.) plants obtained from a LemnaTec Scanalyser automated phenomics platform along with the associated image analysis output and manually acquired biomass data. This series contains 1832 images of 200 diverse safflower genotypes, acquired at the Plant Phenomics Victoria, Horsham, Victoria, Australia. Two Prosilica GT RGB (red-green-blue) cameras were used to generate 6576 × 4384 pixel portable network graphic (PNG) images. Safflower genotypes were either subjected to a salt treatment (250 mM NaCl) or grown as a control (0 mM NaCl) and imaged daily from 15 to 36 days after sowing. Each snapshot consists of four images collected at a point in time; one of which is taken from above (top-view) and the remainder from the side at either 0°, 120° or 240°. The dataset also includes analysis output quantifying traits and describing phenotypes, as well as manually collected biomass and leaf ion content data. The usage of the dataset is already demonstrated in Thoday-Kennedy et al. (2021) [1]. This dataset describes the early growth differences of diverse safflower genotypes and identified genotypes tolerant or susceptible to salinity stress. This dataset provides detailed image analysis parameters for phenotyping a large population of safflower that can be used for the training of image-based trait identification pipelines for a wide range of crop species.

8.
Case Rep Rheumatol ; 2022: 6221640, 2022.
Article in English | MEDLINE | ID: mdl-36317195

ABSTRACT

An elderly man with prostate cancer and a deep vein thrombosis (DVT) of the lower extremity diagnosed 12 days ago on apixaban presented with a new-onset palpable rash on both of his legs. Extensive laboratory workup was largely unremarkable, except for multiple skin punch biopsies revealing deposition of immunoglobulin A (IgA) in the superficial blood vessels with infiltration of leukocytes, concerning for a small vessel vasculitis. Given the temporal association along with the negative workup, the rash was attributed to apixaban, and the anticoagulation regimen was switched to dabigatran. At a 2-week follow-up visit, the patient was asymptomatic and tolerating dabigatran without any adverse events.

9.
Front Plant Sci ; 13: 976375, 2022.
Article in English | MEDLINE | ID: mdl-36352888

ABSTRACT

Ascochyta blight is one of the most destructive diseases in field pea and is caused by either individual or combined infections by the necrotrophic pathogens Peyronellaea pinodes, Didymella pinodella, Ascochyta pisi and Ascochyta koolunga. Knowledge of disease epidemiology will help in understanding the resistance mechanisms, which, in turn, is beneficial in breeding for disease resistance. A pool of breeding lines and cultivars were inoculated with P. pinodes and D. pinodella to study the resistance responses and to characterize the underlying resistance reactions. In general, phenotypic analysis of controlled environment disease assays showed clear differential responses among genotypes against the two pathogens. The released variety PBA Wharton and the breeding line 11HP302-12HO-1 showed high levels of resistance against both pathogens whereas PBA Twilight and 10HP249-11HO-7 showed differential responses between the two pathogens, showing higher resistance against D. pinodella as compared to P. pinodes. OZP1604 had high infection levels against both pathogens. Histochemical analysis of leaves using diamino benzidine (DAB) showed the more resistant genotypes had lower accumulation of hydrogen peroxide compared to susceptible genotypes. The digital images of DAB staining were analyzed using ImageJ, an image analysis software. The image analysis results showed that quantification of leaf disease infection through image analysis is a useful tool in estimating the level of cell death in biotic stress studies. The qRT-PCR analysis of defense related genes showed that partially resistant genotypes had significantly higher expression of PsOXII and Pshmm6 in the P. pinodes treated plants, whereas expression of PsOXII, PsAPX1, PsCHS3 and PsOPR1 increased in partially resistant plants inoculated with D. pinodella. The differential timing and intensity of expression of a range of genes between resistant lines challenged with the same pathogen, or challenged with different pathogens, suggests that there are multiple pathways that restrict infection in this complex pathogen-host interaction. The combination of phenotypic, histochemical and molecular approaches provide a comprehensive picture of the infection process and resistance mechanism of pea plants against these pathogens.

10.
Anal Chem ; 94(39): 13422-13431, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36136056

ABSTRACT

α-Ketoglutarate is a key biomolecule involved in a number of metabolic pathways─most notably the TCA cycle. Abnormal α-ketoglutarate metabolism has also been linked with cancer. Here, isotopic labeling was employed to synthesize [1-13C,5-12C,D4]α-ketoglutarate with the future goal of utilizing its [1-13C]-hyperpolarized state for real-time metabolic imaging of α-ketoglutarate analytes and its downstream metabolites in vivo. The signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH) hyperpolarization technique was used to create 9.7% [1-13C] polarization in 1 minute in this isotopologue. The efficient 13C hyperpolarization, which utilizes parahydrogen as the source of nuclear spin order, is also supported by favorable relaxation dynamics at 0.4 µT field (the optimal polarization transfer field): the exponential 13C polarization buildup constant Tb is 11.0 ± 0.4 s whereas the 13C polarization decay constant T1 is 18.5 ± 0.7 s. An even higher 13C polarization value of 17.3% was achieved using natural-abundance α-ketoglutarate disodium salt, with overall similar relaxation dynamics at 0.4 µT field, indicating that substrate deuteration leads only to a slight increase (∼1.2-fold) in the relaxation rates for 13C nuclei separated by three chemical bonds. Instead, the gain in polarization (natural abundance versus [1-13C]-labeled) is rationalized through the smaller heat capacity of the "spin bath" comprising available 13C spins that must be hyperpolarized by the same number of parahydrogen present in each sample, in line with previous 15N SABRE-SHEATH studies. Remarkably, the C-2 carbon was not hyperpolarized in both α-ketoglutarate isotopologues studied; this observation is in sharp contrast with previously reported SABRE-SHEATH pyruvate studies, indicating that the catalyst-binding dynamics of C-2 in α-ketoglutarate differ from that in pyruvate. We also demonstrate that 13C spectroscopic characterization of α-ketoglutarate and pyruvate analytes can be performed at natural 13C abundance with an estimated detection limit of 80 micromolar concentration × *%P13C. All in all, the fundamental studies reported here enable a wide range of research communities with a new hyperpolarized contrast agent potentially useful for metabolic imaging of brain function, cancer, and other metabolically challenging diseases.


Subject(s)
Ketoglutaric Acids , Theophylline , Catalysis , Contrast Media , Pyruvic Acid
11.
Front Plant Sci ; 13: 923381, 2022.
Article in English | MEDLINE | ID: mdl-35837454

ABSTRACT

Field pea is the most commonly grown temperate pulse crop, with close to 15 million tons produced globally in 2020. Varieties improved through breeding are important to ensure ongoing improvements in yield and disease resistance. Genomic selection (GS) is a modern breeding approach that could substantially improve the rate of genetic gain for grain yield, and its deployment depends on the prediction accuracy (PA) that can be achieved. In our study, four yield trials representing breeding lines' advancement stages of the breeding program (S0, S1, S2, and S3) were assessed with grain yield, aerial high-throughput phenotyping (normalized difference vegetation index, NDVI), and bacterial blight disease scores (BBSC). Low-to-moderate broad-sense heritability (0.31-0.71) and narrow-sense heritability (0.13-0.71) were observed, as the estimated additive and non-additive genetic components for the three traits varied with the different models fitted. The genetic correlations among the three traits were high, particularly in the S0-S2 stages. NDVI and BBSC were combined to investigate the PA for grain yield by univariate and multivariate GS models, and multivariate models showed higher PA than univariate models in both cross-validation and forward prediction methods. A 6-50% improvement in PA was achieved when multivariate models were deployed. The highest PA was indicated in the forward prediction scenario when the training population consisted of early generation breeding stages with the multivariate models. Both NDVI and BBSC are commonly used traits that could be measured in the early growth stage; however, our study suggested that NDVI is a more useful trait to predict grain yield with high accuracy in the field pea breeding program, especially in diseased trials, through its incorporation into multivariate models.

12.
Front Plant Sci ; 12: 662498, 2021.
Article in English | MEDLINE | ID: mdl-34220887

ABSTRACT

Salinity is a major contributing factor to the degradation of arable land, and reductions in crop growth and yield. To overcome these limitations, the breeding of crop varieties with improved salt tolerance is needed. This requires effective and high-throughput phenotyping to optimize germplasm enhancement. Safflower (Carthamus tinctorius L.), is an underappreciated but highly versatile oilseed crop, capable of growing in saline and arid environments. To develop an effective and rapid phenotyping protocol to differentiate salt responses in safflower genotypes, experiments were conducted in the automated imaging facility at Plant Phenomics Victoria, Horsham, focussing on digital phenotyping at early vegetative growth. The initial experiment, at 0, 125, 250, and 350 mM sodium chloride (NaCl), showed that 250 mM NaCl was optimum to differentiate salt sensitive and tolerant genotypes. Phenotyping of a diverse set of 200 safflower genotypes using the developed protocol defined four classes of salt tolerance or sensitivity, based on biomass and ion accumulation. Salt tolerance in safflower was dependent on the exclusion of Na+ from shoot tissue and the maintenance of K+ uptake. Salinity response identified in glasshouse experiments showed some consistency with the performance of representatively selected genotypes tested under sodic field conditions. Overall, our results suggest that digital phenotyping can be an effective high-throughput approach in identifying candidate genotypes for salt tolerance in safflower.

13.
PLoS One ; 16(7): e0254908, 2021.
Article in English | MEDLINE | ID: mdl-34297757

ABSTRACT

Drought is one of the most severe and unpredictable abiotic stresses, occurring at any growth stage and affecting crop yields worldwide. Therefore, it is essential to develop drought tolerant varieties to ensure sustainable crop production in an ever-changing climate. High-throughput digital phenotyping technologies in tandem with robust screening methods enable precise and faster selection of genotypes for breeding. To investigate the use of digital imaging to reliably phenotype for drought tolerance, a genetically diverse safflower population was screened under different drought stresses at Agriculture Victoria's high-throughput, automated phenotyping platform, Plant Phenomics Victoria, Horsham. In the first experiment, four treatments, control (90% field capacity; FC), 40% FC at initial branching, 40% FC at flowering and 50% FC at initial branching and flowering, were applied to assess the performance of four safflower genotypes. Based on these results, drought stress using 50% FC at initial branching and flowering stages was chosen to further screen 200 diverse safflower genotypes. Measured plant traits and dry biomass showed high correlations with derived digital traits including estimated shoot biomass, convex hull area, caliper length and minimum area rectangle, indicating the viability of using digital traits as proxy measures for plant growth. Estimated shoot biomass showed close association having moderately high correlation with drought indices yield index, stress tolerance index, geometric mean productivity, and mean productivity. Diverse genotypes were classified into four clusters of drought tolerance based on their performance (seed yield and digitally estimated shoot biomass) under stress. Overall, results show that rapid and precise image-based, high-throughput phenotyping in controlled environments can be used to effectively differentiate response to drought stress in a large numbers of safflower genotypes.


Subject(s)
Carthamus tinctorius/genetics , Droughts , Genotype , Phenomics/methods , Plant Breeding/methods , Stress, Physiological , Automation, Laboratory/methods , Biomass , Carthamus tinctorius/physiology , Phenotype
15.
Pharmaceuticals (Basel) ; 14(4)2021 Apr 13.
Article in English | MEDLINE | ID: mdl-33924320

ABSTRACT

Capsules are one of the major solid dosage forms available in a variety of compositions and shapes. Developments in this dosage form are not new, but the production of non-gelatin capsules is a recent trend. In pharmaceutical as well as other biomedical research, alginate has great versatility. On the other hand, the use of inorganic material to enhance material strength is a common research topic in tissue engineering. The research presented here is a combination of qualities of alginate and montmorillonite (MMT). These two materials were used in this research to produce a soft non-gelatin modified-release capsule. Moreover, the research describes a facile benchtop production of these capsules. The produced capsules were critically analyzed for their appearance confirming resemblance with marketed capsules, functionality in terms of drug encapsulation, as well as release and durability.

16.
Chemistry ; 27(38): 9727-9736, 2021 Jul 07.
Article in English | MEDLINE | ID: mdl-33856077

ABSTRACT

NMR hyperpolarization techniques enhance nuclear spin polarization by several orders of magnitude resulting in corresponding sensitivity gains. This enormous sensitivity gain enables new applications ranging from studies of small molecules by using high-resolution NMR spectroscopy to real-time metabolic imaging in vivo. Several hyperpolarization techniques exist for hyperpolarization of a large repertoire of nuclear spins, although the 13 C and 15 N sites of biocompatible agents are the key targets due to their widespread use in biochemical pathways. Moreover, their long T1 allows hyperpolarized states to be retained for up to tens of minutes. Signal amplification by reversible exchange (SABRE) is a low-cost and ultrafast hyperpolarization technique that has been shown to be versatile for the hyperpolarization of 15 N nuclei. Although large sensitivity gains are enabled by hyperpolarization, 15 N natural abundance is only ∼0.4 %, so isotopic labeling of the molecules to be hyperpolarized is required in order to take full advantage of the hyperpolarized state. Herein, we describe selected advances in the preparation of 15 N-labeled compounds with the primary emphasis on using these compounds for SABRE polarization in microtesla magnetic fields through spontaneous polarization transfer from parahydrogen. Also, these principles can certainly be applied for hyperpolarization of these emerging contrast agents using dynamic nuclear polarization and other techniques.


Subject(s)
Magnetic Fields , Magnetic Resonance Imaging , Isotope Labeling , Magnetic Resonance Spectroscopy , Molecular Imaging
17.
World J Gastroenterol ; 26(43): 6891-6908, 2020 Nov 21.
Article in English | MEDLINE | ID: mdl-33268969

ABSTRACT

BACKGROUND: While Crohn's disease has been studied extensively in high-income countries, its epidemiology and care in low and lower-middle income countries (LLMICs) is not well established due to a lack of disease registries and diagnostic capacity. AIM: To describe the published burden, diagnostic/treatment capacity, service utilization, challenges/barriers to individuals with Crohn's in LLMICs and their providers. METHODS: We conducted a scoping review utilizing a full search strategy was developed and conducted in PubMed, Embase and World Health Organization Global Index Medicus. Two independent reviewers screened the titles and abstracts of all of the publications found in this search, reviewed selected publications, and extracted relevant data, which underwent descriptive review and was analyzed in Excel. RESULTS: The database search yielded 4486 publications, 216 of which were determined to be relevant to the research questions. Of all 79 LLMICs, only 21 (26.6%) have publications describing individuals with Crohn's. Overall, the highest number of studies came from India, followed by Tunisia, and Egypt. The mean number of Crohn's patients reported per study is 57.84 and the median is 22, with a wide range from one to 980. CONCLUSION: This scoping review has shown that, although there is a severe lack of population-based data about Crohn's in LLMICs, there is a signal of Crohn's in these settings around the world.


Subject(s)
Crohn Disease , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Crohn Disease/therapy , Developing Countries , Egypt , Humans , India , Remission Induction , Tunisia
18.
J Exp Bot ; 71(15): 4604-4615, 2020 07 25.
Article in English | MEDLINE | ID: mdl-32185382

ABSTRACT

The development of crop varieties with higher nitrogen use efficiency is crucial for sustainable crop production. Combining high-throughput genotyping and phenotyping will expedite the discovery of novel alleles for breeding crop varieties with higher nitrogen use efficiency. Digital and hyperspectral imaging techniques can efficiently evaluate the growth, biophysical, and biochemical performance of plant populations by quantifying canopy reflectance response. Here, these techniques were used to derive automated phenotyping of indicator biomarkers, biomass and chlorophyll levels, corresponding to different nitrogen levels. A detailed description of digital and hyperspectral imaging and the associated challenges and required considerations are provided, with application to delineate the nitrogen response in wheat. Computational approaches for spectrum calibration and rectification, plant area detection, and derivation of vegetation index analysis are presented. We developed a novel vegetation index with higher precision to estimate chlorophyll levels, underpinned by an image-processing algorithm that effectively removed background spectra. Digital shoot biomass and growth parameters were derived, enabling the efficient phenotyping of wheat plants at the vegetative stage, obviating the need for phenotyping until maturity. Overall, our results suggest value in the integration of high-throughput digital and spectral phenomics for rapid screening of large wheat populations for nitrogen response.


Subject(s)
Nitrogen , Plant Leaves , Biomarkers , Genotype , Hyperspectral Imaging , Plant Breeding
19.
Front Plant Sci ; 10: 1285, 2019.
Article in English | MEDLINE | ID: mdl-31681380

ABSTRACT

Delaying leaf senescence in plants, especially under water stress conditions, can help to maintain the remobilization of stored nutrients in source-sink relationships, thus leading to improved crop yields. Leaf senescence can be delayed by plant hormones such as cytokinin. Here, the Isopentenyl transferase (IPT) gene, encoding a cytokinin biosynthesis enzyme, driven by a modified AtMYB32xs promoter was transformed into wheat. Transgenic wheat plants exhibited delayed leaf senescence, retaining chlorophyll for longer under controlled environment conditions. Selected independent transgenic events and their corresponding nulls were grown under field conditions for two consecutive years under well-watered and water stress treatments using automated rainout shelters. Three independent transgenic events had improved canopy green cover, lower canopy temperatures, and higher leaf water potential than their respective non-transgenic nulls, with no abnormality in morphology and phenology. Increased grain yield was observed in transgenic events under both water treatments, with the yield increase more pronounced under water stress (26-42%). These results have shown that delayed leaf senescence using the chimeric transgene AtMYB32xs-p::IPT can be a useful strategy to achieve grain yield gains in wheat and potentially other crops for sustainable food production.

20.
Expert Opin Drug Deliv ; 16(9): 969-980, 2019 09.
Article in English | MEDLINE | ID: mdl-31382795

ABSTRACT

Introduction: Human respiratory syncytial virus (RSV) is a common respiratory virus that causes severe lower respiratory tract infection in infants, children and aged adults. Currently, there is no active prophylaxis present in the market for RSV infection; however, there are over a dozen compounds being tested in the laboratory as well as clinical trials. To increase the efficiency and safety of these therapeutics, there is a need for delivery vehicles. Areas covered: Liposomes can be used for delivering anti-RSV agents with the advantage of modulating and eliciting the desired adjuvant effect by the different combination of lipids. This review discusses the promising application of liposome for anti-RSV therapeutics. Expert opinion: Liposomes are attracting attention for delivery of pulmonary therapeutics, since they offer compatibility for delivering drugs, vaccines and other therapeutic molecules. Variation in liposome size and composition gives flexibility for the amount and number of deliverables, whilst targeted delivery with the capability for immunomodulation makes liposomes a promising candidate for RSV therapeutic applications.


Subject(s)
Antiviral Agents/administration & dosage , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Vaccines/administration & dosage , Animals , Humans , Liposomes
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