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1.
J Wound Care ; 33(Sup5b): S4-S11, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38752844

RESUMO

It is now assumed that all hard-to-heal wounds contain biofilm. Debridement plays a key role in wound-bed preparation, as it can remove biofilm along with the devitalised tissue, potentially leaving a clean wound bed that is more likely to progress towards healing. The gold standard methods of debridement (surgical and sharp) are the least used, as they require specialist training and are often not readily available at the point of need. Most other methods can be used by generalists but are slower. They all need regular applications. The topical desiccating agent DEBRICHEM is an innovative alternative, as it is fast, effective and can be used in all clinical settings, as well as typically requiring only a single use. This article describes best practice for achieving optimal outcomes with its use.


Assuntos
Biofilmes , Desbridamento , Cicatrização , Humanos , Administração Tópica , Desbridamento/métodos , Infecção dos Ferimentos/terapia , Ferimentos e Lesões/terapia
2.
PLoS One ; 19(5): e0296547, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753661

RESUMO

Endophytic bacteria, recognized as eco-friendly biofertilizers, have demonstrated the potential to enhance crop growth and yield. While the plant growth-promoting effects of endophytic bacteria have been extensively studied, the impact of weed endophytes remains less explored. In this study, we aimed to isolate endophytic bacteria from native weeds and assess their plant growth-promoting abilities in rice under varying chemical fertilization. The evaluation encompassed measurements of mineral phosphate and potash solubilization, as well as indole-3-acetic acid (IAA) production activity by the selected isolates. Two promising strains, tentatively identified as Alcaligenes faecalis (BTCP01) from Eleusine indica (Goose grass) and Metabacillus indicus (BTDR03) from Cynodon dactylon (Bermuda grass) based on 16S rRNA gene phylogeny, exhibited noteworthy phosphate and potassium solubilization activity, respectively. BTCP01 demonstrated superior phosphate solubilizing activity, while BTDR03 exhibited the highest potassium (K) solubilizing activity. Both isolates synthesized IAA in the presence of L-tryptophan, with the detection of nifH and ipdC genes in their genomes. Application of isolates BTCP01 and BTDR03 through root dipping and spraying at the flowering stage significantly enhanced the agronomic performance of rice variety CV. BRRI dhan29. Notably, combining both strains with 50% of recommended N, P, and K fertilizer doses led to a substantial increase in rice grain yields compared to control plants receiving 100% of recommended doses. Taken together, our results indicate that weed endophytic bacterial strains BTCP01 and BTDR03 hold promise as biofertilizers, potentially reducing the dependency on chemical fertilizers by up to 50%, thereby fostering sustainable rice production.


Assuntos
Alcaligenes faecalis , Endófitos , Fertilizantes , Oryza , Fosfatos , Plantas Daninhas , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Endófitos/metabolismo , Alcaligenes faecalis/metabolismo , Alcaligenes faecalis/crescimento & desenvolvimento , Plantas Daninhas/microbiologia , Plantas Daninhas/crescimento & desenvolvimento , Fosfatos/metabolismo , Ácidos Indolacéticos/metabolismo , RNA Ribossômico 16S/genética , Filogenia , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Eleusine/microbiologia , Eleusine/crescimento & desenvolvimento , Cynodon/microbiologia , Cynodon/crescimento & desenvolvimento , Potássio/metabolismo
3.
Front Microbiol ; 15: 1336515, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529179

RESUMO

Crop production often faces challenges from plant diseases, and biological control emerges as an effective, environmentally friendly, cost-effective, and sustainable alternative to chemical control. Wheat blast disease caused by fungal pathogen Magnaporthe oryzae Triticum (MoT), is a potential catastrophic threat to global food security. This study aimed to identify potential bacterial isolates from rice and wheat seeds with inhibitory effects against MoT. In dual culture and seedling assays, three bacterial isolates (BTS-3, BTS-4, and BTLK6A) demonstrated effective suppression of MoT growth and reduced wheat blast severity when artificially inoculated at the seedling stage. Genome phylogeny identified these isolates as Bacillus subtilis (BTS-3) and B. velezensis (BTS-4 and BTLK6A). Whole-genome analysis revealed the presence of genes responsible for controlling MoT through antimicrobial defense, antioxidant defense, cell wall degradation, and induced systemic resistance (ISR). Taken together, our results suggest that the suppression of wheat blast disease by seed endophytic B. subtilis (BTS-3) and B. velezensis (BTS-4 and BTLK6A) is liked with antibiosis and induced systemic resistance to wheat plants. A further field validation is needed before recommending these endophytic bacteria for biological control of wheat blast.

4.
Plant Genome ; 16(4): e20397, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37885362

RESUMO

Vernalization requirement is an integral component of flowering in winter-type plants. The availability of winter ecotypes among Camelina species facilitated the mapping of quantitative trait loci (QTL) for vernalization requirement in Camelina sativa. An inter and intraspecific crossing scheme between related Camelina species, where one spring and two different sources of winter-type habit were used, resulted in the development of two segregating populations. Linkage maps generated with sequence-based markers identified three QTLs associated with vernalization requirement in C. sativa; two from the interspecific (chromosomes 13 and 20) and one from the intraspecific cross (chromosome 8). Notably, the three loci were mapped to different homologous regions of the hexaploid C. sativa genome. All three QTLs were found in proximity to Flowering Locus C (FLC), variants of which have been reported to affect the vernalization requirement in plants. Temporal transcriptome analysis for winter-type Camelina alyssum demonstrated reduction in expression of FLC on chromosomes 13 and 20 during cold treatment, which would trigger flowering, since FLC would be expected to suppress floral initiation. FLC on chromosome 8 also showed reduced expression in the C. sativa ssp. pilosa winter parent upon cold treatment, but was expressed at very high levels across all time points in the spring-type C. sativa. The chromosome 8 copy carried a deletion in the spring-type line, which could impact its functionality. Contrary to previous reports, all three FLC loci can contribute to controlling the vernalization response in C. sativa and provide opportunities for manipulating this requirement in the crop.


Assuntos
Arabidopsis , Locos de Características Quantitativas , Vernalização , Flores , Mapeamento Cromossômico , Arabidopsis/genética
5.
Front Microbiol ; 14: 1212505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520368

RESUMO

Plant probiotic bacteria enhance growth and yield of crop plants when applied at the appropriate time and dose. Two rice probiotic bacteria, Paraburkholderia fungorum strain BRRh-4 and Delftia sp. strain BTL-M2 promote growth and yield of plants. However, no information is available on application of these two bacteria on growth, yield, and diversity and population of bacteriome in roots and rhizosphere soils of the treated rice plants. This study aimed to assess the effect of BRRh-4 and BTL-M2 application on growth, yield and bacteriome in roots and rhizosphere soil of rice under varying doses of N, P and K fertilizers. Application of BRRh-4 and BTL-M2 strains significantly (p < 0.05) increased seed germination, growth and yield of rice compared to an untreated control. Interestingly, the grain yield of rice by these bacteria with 50% less of the recommended doses of N, P, and K fertilizers were statistically similar to or better than the rice plants treated with 100% doses of these fertilizers. Targeted amplicon (16S rRNA) sequence-based analysis revealed significant differences (PERMANOVA, p = 0.00035) in alpha-diversity between the root (R) and rhizosphere soil (S) samples, showing higher diversity in the microbial ecosystem of root samples. Additionally, the bacteriome diversity in the root of rice plants that received both probiotic bacteria and chemical fertilizers were significantly higher (PERMANOVA, p = 0.0312) compared to the rice plants treated with fertilizers only. Out of 185 bacterial genera detected, Prevotella, an anaerobic and Gram-negative bacterium, was found to be the predominant genus in both rhizosphere soil and root metagenomes. However, the relative abundance of Prevotella remained two-fold higher in the rhizosphere soil metagenome (52.02%) than in the root metagenome (25.04%). The other predominant bacterial genera detected in the rice root metagenome were Bacillus (11.07%), Planctomyces (4.06%), Faecalibacterium (3.91%), Deinococcus (2.97%), Bacteroides (2.61%), and Chryseobacterium (2.30%). On the other hand, rhizosphere soil metagenome had Bacteroides (12.38%), Faecalibacterium (9.50%), Vibrio (5.94%), Roseomonas (3.40%), and Delftia (3.02%). Interestingly, we found the presence and/or abundance of specific genera of bacteria in rice associated with the application of a specific probiotic bacterium. Taken together, our results indicate that improvement of growth and yield of rice by P. fungorum strain BRRh-4 and Delftia sp. strain BTL-M2 is likely linked with modulation of diversity, structures, and signature of bacteriome in roots and rhizosphere soils. This study for the first time demonstrated that application of plant growth promoting bacteria significantly improve growth, yield and increase the diversity of bacterial community in rice.

6.
Int Wound J ; 20(9): 3467-3473, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37139846

RESUMO

The aim of this article is to identify and describe clinical practice performance characteristics for bordered foam dressings in the treatment of complex wounds. Our recently published systematic review of outcomes and applied measurement instruments for the use of bordered foam dressings in complex wounds has led to us identifying a range of important clinical and patient-centred issues related to this dressing class. Specifically, here, we focus on an overview of performance criteria in the areas of application, adhesion, exudate management and debridement functions of bordered foam dressings. Our hope is that by highlighting the clinical performance criteria, future testing standards for wound dressings will more closely match our clinical expectations and, thereby, assist clinicians to make better wound treatment choices based on meaningful and clinically relevant dressing product performance standards. complex wounds, complex wound care, treatment, bordered foam dressings, dressing performance.


Assuntos
Bandagens , Cicatrização , Humanos , Seleção de Pacientes , Exsudatos e Transudatos
7.
J Tissue Viability ; 32(3): 430-436, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37127485

RESUMO

AIM: The aim of this project was to develop a core outcome set (COS) for clinical effectiveness studies of bordered foam dressings in the treatment of complex wounds. METHODS: The research project followed the Core Outcome Measures in Effectiveness Trials (COMET) initiative and consisted of two phases. The first phase prepared the background and process, while the second phase had three steps: outcome list generation via systematic review and qualitative study, Delphi consensus study, and consensus meeting. The study has been registered in the Core Outcome Measures in Effectiveness Trials database. RESULTS: The systematic review resulted in 82 outcomes and 20 additional outcomes were obtained during the interviews. After refinement, 111 panellists from 23 countries rated a list of 51 outcomes. In the following consensus meeting, six outcomes were prioritized to be included in the core outcome set. After the consensus meeting, a patient-reported outcome was added to the core outcome set. CONCLUSION: The COS for evaluating the effectiveness of bordered foam dressings in treating complex wounds includes 7 outcomes: "ability to stay in place", "leakage", "pain", "dressing related periwound skin changes", "change in wound size over time", and "overall satisfaction". These identified outcomes are correlated with contemporary bioengineering testing and evaluation methods for dressing performance, which underpins the need for a close multidisciplinary collaboration to advance the field of wound dressings. The outcome 'overall satisfaction' reflects the impact of complex wounds and their treatment on a patient's daily life. The use of these outcomes is recommended to improve data synthesis and promote evidence-based practice. Future developments in COS development involve creating measurement instruments and relevant endpoints for these outcomes.


Assuntos
Bandagens , Avaliação de Resultados em Cuidados de Saúde , Humanos , Técnica Delphi , Determinação de Ponto Final/métodos , Resultado do Tratamento , Revisões Sistemáticas como Assunto
8.
Foot Ankle Surg ; 29(3): 218-222, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36646595

RESUMO

BACKGROUND: Forefoot ulceration in diabetes requires significant resources, with high cost and low rates of success. The authors present the results of tendon procedures (percutaneous toe tenotomy and percutaneous tendo-achilles lengthening) under local anaesthetic to adjust mechanics in patients with diabetic neuropathic forefoot ulceration. METHODS: Retrospective review of electronic patient record of 19 patients (22 feet) undergoing local anaesthetic tendon procedures between April 2019 and April 2021 with a 12 month follow up period. Size of ulcer, rate of ulcer healing, complication rates and ulcer recurrence were recorded and compared to a population of conservatively-managed patients (14 patients, 15 feet) treated prior to the introduction of tendon procedures. All clinical information obtained from electronic patient records. RESULTS: All patients undergoing tendon procedures achieved complete ulcer healing at a mean time of 3.3 weeks for toe tip ulcers (after toe tenotomy) and 4.5 weeks for metatarsal head ulcers (after Achilles lengthening). There were no admissions for diabetic foot sepsis, reduced recurrence, reduced amputation rates and no mortality. Of the conservatively managed cohort, only 3 of the 15 achieved ulcer resolution without recurrence within the 12 month study period. The cohort managed conservatively had an average cost of £ 9902 per patient, per annum. The intervention cost was £ 1211 per patient, saving an average of £ 8691 per patient, per annum with ulcer resolution (88 % reduction in costs). CONCLUSION: Significant patient benefit, reduction in resource use and cost saving was seen with this simple intervention, which merits full evaluation in a clinical trial. LEVEL OF EVIDENCE: Level-IV.


Assuntos
Tendão do Calcâneo , Pé Diabético , Úlcera do Pé , Ortopedia , Humanos , Tendão do Calcâneo/cirurgia , Anestésicos Locais , Úlcera do Pé/etiologia , Tenotomia/métodos , Úlcera/etiologia , Estudos Retrospectivos
9.
Plant J ; 114(1): 209-224, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36710629

RESUMO

Reproductive success hinges on precisely coordinated meiosis, yet our understanding of how structural rearrangements of chromatin and phase transitions during meiosis are transcriptionally regulated is limited. In crop plants, detailed analysis of the meiotic transcriptome could identify regulatory genes and epigenetic regulators that can be targeted to increase recombination rates and broaden genetic variation, as well as provide a resource for comparison among eukaryotes of different taxa to answer outstanding questions about meiosis. We conducted a meiotic stage-specific analysis of messenger RNA (mRNA), small non-coding RNA (sncRNA), and long intervening/intergenic non-coding RNA (lincRNA) in wheat (Triticum aestivum L.) and revealed novel mechanisms of meiotic transcriptional regulation and meiosis-specific transcripts. Amidst general repression of mRNA expression, significant enrichment of ncRNAs was identified during prophase I relative to vegetative cells. The core meiotic transcriptome was comprised of 9309 meiosis-specific transcripts, 48 134 previously unannotated meiotic transcripts, and many known and novel ncRNAs differentially expressed at specific stages. The abundant meiotic sncRNAs controlled the reprogramming of central metabolic pathways by targeting genes involved in photosynthesis, glycolysis, hormone biosynthesis, and cellular homeostasis, and lincRNAs enhanced the expression of nearby genes. Alternative splicing was not evident in this polyploid species, but isoforms were switched at phase transitions. The novel, stage-specific regulatory controls uncovered here challenge the conventional understanding of this crucial biological process and provide a new resource of requisite knowledge for those aiming to directly modulate meiosis to improve crop plants. The wheat meiosis transcriptome dataset can be queried for genes of interest using an eFP browser located at https://bar.utoronto.ca/efp_wheat/cgi-bin/efpWeb.cgi?dataSource=Wheat_Meiosis.


Assuntos
Transcriptoma , Triticum , Triticum/genética , Triticum/metabolismo , Meiose/genética , RNA Mensageiro/genética , RNA não Traduzido/genética
10.
Plant Biotechnol J ; 21(3): 521-535, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36398722

RESUMO

Camelina neglecta is a diploid species from the genus Camelina, which includes the versatile oilseed Camelina sativa. These species are closely related to Arabidopsis thaliana and the economically important Brassica crop species, making this genus a useful platform to dissect traits of agronomic importance while providing a tool to study the evolution of polyploids. A highly contiguous chromosome-level genome sequence of C. neglecta with an N50 size of 29.1 Mb was generated utilizing Pacific Biosciences (PacBio, Menlo Park, CA) long-read sequencing followed by chromosome conformation phasing. Comparison of the genome with that of C. sativa shows remarkable coincidence with subgenome 1 of the hexaploid, with only one major chromosomal rearrangement separating the two. Synonymous substitution rate analysis of the predicted 34 061 genes suggested subgenome 1 of C. sativa directly descended from C. neglecta around 1.2 mya. Higher functional divergence of genes in the hexaploid as evidenced by the greater number of unique orthogroups, and differential composition of resistant gene analogs, might suggest an immediate adaptation strategy after genome merger. The absence of genome bias in gene fractionation among the subgenomes of C. sativa in comparison with C. neglecta, and the complete lack of fractionation of meiosis-specific genes attests to the neopolyploid status of C. sativa. The assembled genome will provide a tool to further study genome evolution processes in the Camelina genus and potentially allow for the identification and exploitation of novel variation for Camelina crop improvement.


Assuntos
Arabidopsis , Brassica , Brassicaceae , Neglecta , Diploide , Brassicaceae/genética , Arabidopsis/genética , Brassica/genética , Genoma de Planta
11.
J Clin Nurs ; 32(15-16): 4730-4740, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36097436

RESUMO

AIMS AND OBJECTIVES: Surveillance of wound infection including signs of infection alongside antimicrobial usage (types, duration, frequency) can highlight knowledge gaps and inconsistencies. This manuscript aims to highlight these, identify and inform opportunities for practice improvement and to show impact of infection management practice may be having on the issue of antimicrobial resistance. BACKGROUND: Infected wounds pose challenges to healthcare professionals. Balancing risk of wound deterioration and progression to systemic infection with appropriate use of antimicrobials is necessary to minimise development of resistance. METHODS: Analysis consisted of a practice survey of 9661 wounds across 70 community sites over a period of one week. Data were collected from projects between 2017 and 2020. The form was available to providers within the UK, Ireland, Norway, Denmark, Sweden and Finland. EQUATOR research guidelines were followed; STROBE checklist for observational research reporting was completed. RESULTS: Infection rates of 8.9% were reported from wounds assessed. These data indicate inconsistencies with diagnosis across practice with non-specialists more likely to be unsure of wound infection. Greater confidence in infection identification was observed as number of signs increased. Inconsistencies were also observed in appropriate treatment; antimicrobials were used in 35% of wounds considered not infected and not used in 41% of wounds that were identified as infected. CONCLUSIONS: This investigation of infection management practice of over 9000 wounds provides an insight into diagnosis and treatment of infection. Inconsistencies in diagnosis and treatment of wound infections reported highlight the need for increased education, awareness of diagnosis and treatment of infection. RELEVANCE TO CLINICAL PRACTICE: Variability in management of infected wounds highlights opportunities to aid more effective diagnosis and treatment of infected wounds. Incorporation of support tools or evidence-based pathways into practice may enhance confidence in management of local infection, balanced with appropriate use, potentially minimising resistance and improving outcomes.


Assuntos
Anti-Infecciosos , Infecção dos Ferimentos , Humanos , Irlanda , Anti-Infecciosos/uso terapêutico , Infecção dos Ferimentos/diagnóstico , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/epidemiologia , Países Escandinavos e Nórdicos , Reino Unido
13.
ACS Med Chem Lett ; 13(8): 1321-1328, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35978696

RESUMO

The NLRP3 inflammasome is a multiprotein complex that facilitates activation and release of the proinflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 in response to infection or endogenous stimuli. It can be inappropriately activated by a range of danger signals resulting in chronic, low-grade inflammation underlying a multitude of diseases, such as Alzheimer's disease, Parkinson's disease, osteoarthritis, and gout. The discovery of potent and specific NLRP3 inhibitors could reduce the burden of several common morbidities. In this study, we identified a weakly potent triazolopyrimidone hit (1) following an in silico modeling exercise. This was optimized to furnish potent and selective small molecule NLRP3 inflammasome inhibitors. Compounds such as NDT-30805 could be useful tool molecules for a scaffold-hopping or pharmacophore generation project or used as leads toward the development of clinical candidates.

14.
G3 (Bethesda) ; 12(9)2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-35900169

RESUMO

Population structure (also called genetic structure and population stratification) is the presence of a systematic difference in allele frequencies between subpopulations in a population as a result of nonrandom mating between individuals. It can be informative of genetic ancestry, and in the context of medical genetics, it is an important confounding variable in genome-wide association studies. Recently, many nonlinear dimensionality reduction techniques have been proposed for the population structure visualization task. However, an objective comparison of these techniques has so far been missing from the literature. In this article, we discuss the previously proposed nonlinear techniques and some of their potential weaknesses. We then propose a novel quantitative evaluation methodology for comparing these nonlinear techniques, based on populations for which pedigree is known a priori either through artificial selection or simulation. Based on this evaluation metric, we find graph-based algorithms such as t-SNE and UMAP to be superior to principal component analysis, while neural network-based methods fall behind.


Assuntos
Algoritmos , Estudo de Associação Genômica Ampla , Simulação por Computador , Frequência do Gene , Genética Populacional , Estudo de Associação Genômica Ampla/métodos , Humanos , Análise de Componente Principal
15.
J Tissue Viability ; 31(3): 514-522, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35610151

RESUMO

OBJECTIVE: The aim of this review article was to identify reported outcomes and measurement instruments used in clinical research on bordered foam dressings in the treatment of complex wounds. METHODS: MEDLINE (PubMed interface), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, and The Cochrane Library were systematically searched using a combination of key terms including; wounds, bordered foam dressing, and treatment. Studies were included if they (1) targeted an adult population, (2) addressed the treatment of complex wounds with a bordered foam dressing as the primary wound dressing, (3) were retrieved from original research, and (4) were published between 2000 and 2022. There were no restrictions on language or study design. Studies that focused primarily on the prevention of complex wounds were excluded. Data extraction included outcome domains, outcomes, instruments, time points, and outcome measures. The OMERACT Filter 2.0 was used as a conceptual framework for the extraction of outcomes. RESULTS: A total of 24 outcome domains and 82 outcomes were identified. The outcomes were categorised into five core areas: (1) impact on life, (2) dressing performance, (3) pathophysiological manifestations, (4) resource use, and (5) adverse events. Thirtynine outcomes (47.0%) were measured at more than one time point. The most frequently reported time point was 'at the end of treatment' (62.7%). Outcomes were measured using self-report instruments, clinical observations, and bio-physiological instruments. CONCLUSION: This systematic review identified reported outcomes and measurement instruments in research on bordered foam dressings in the treatment of complex wounds. The variety and lack of consistency in terms of instruments, time points and outcome measurements made it difficult to compare data directly across different reported studies. A solution to the variety in outcome reporting across studies in complex wound care, and moreover for the treatment with bordered foam dressings, is the development of a Core Outcome Set (COS). The outcomes in this review article will inform the next steps of developing a COS, where patients, clinicians and researchers will be involved to decide on the final outcomes included in a COS for the treatment of complex wounds with bordered foam dressings.


Assuntos
Bandagens , Cicatrização , Adulto , Humanos , Medidas de Resultados Relatados pelo Paciente
16.
J Med Chem ; 65(9): 6775-6802, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35482677

RESUMO

d-Serine is a coagonist of the N-methyl d-aspartate (NMDA) receptor, a key excitatory neurotransmitter receptor. In the brain, d-serine is synthesized from its l-isomer by serine racemase and is metabolized by the D-amino acid oxidase (DAO, DAAO). Many studies have linked decreased d-serine concentration and/or increased DAO expression and enzyme activity to NMDA dysfunction and schizophrenia. Thus, it is feasible to employ DAO inhibitors for the treatment of schizophrenia and other indications. Powered by the Schrödinger computational modeling platform, we initiated a research program to identify novel DAO inhibitors with the best-in-class properties. The program execution leveraged an hDAO FEP+ model to prospectively predict compound potency. A new class of DAO inhibitors with desirable properties has been discovered from this endeavor. Our modeling technology on this program has not only enhanced the efficiency of structure-activity relationship development but also helped to identify a previously unexplored subpocket for further optimization.


Assuntos
N-Metilaspartato , Esquizofrenia , D-Aminoácido Oxidase/metabolismo , Humanos , Receptores de N-Metil-D-Aspartato/metabolismo , Serina/metabolismo , Relação Estrutura-Atividade
17.
BMC Genomics ; 23(1): 228, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321662

RESUMO

BACKGROUND: The tall wheatgrass species Thinopyrum elongatum carries a strong fusarium head blight (FHB) resistance locus located on the long arm of chromosome 7 (7EL) as well as resistance to leaf and stem rusts, all diseases with a significant impact on wheat production. Towards understanding the contribution of Th. elongatum 7EL to improvement of disease resistance in wheat, the genomic sequence of the 7EL fragment present in the wheat Chinese Spring (CS) telosomic addition line CS-7EL was determined and the contribution and impact of 7EL on the rachis transcriptome during FHB infection was compared between CS and CS-7EL. RESULTS: We assembled the Th. elongatum 7EL chromosome arm using a reference-guided approach. Combining this assembly with the available reference sequence for CS hexaploid wheat provided a reliable reference for interrogating the transcriptomic differences in response to infection conferred by the 7EL fragment. Comparison of the transcriptomes of rachis tissues from CS and CS-7EL showed expression of Th. elongatum transcripts as well as modulation of wheat transcript expression profiles in the CS-7EL line. Expression profiles at 4 days after infection with Fusarium graminearum, the causal agent of FHB, showed an increased in expression of genes associated with an effective defense response, in particular glucan endo-1,3-beta-glucosidases and chitinases, in the FHB-resistant line CS-7EL while there was a larger increase in differential expression for genes associated with the level of fungal infection in the FHB-susceptible line CS. One hundred and seven 7EL transcripts were expressed in the smallest 7EL region defined to carry FHB resistance. CONCLUSION: 7EL contributed to CS-7EL transcriptome by direct expression and through alteration of wheat transcript profiles. FHB resistance in CS-7EL was associated with transcriptome changes suggesting a more effective defense response. A list of candidate genes for the FHB resistance locus on 7EL has been established.


Assuntos
Cromossomos de Plantas , Resistência à Doença , Fusarium , Doenças das Plantas , Poaceae , Cromossomos de Plantas/genética , Resistência à Doença/genética , Genômica , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Poaceae/genética , Poaceae/microbiologia , Transcriptoma
18.
PLoS One ; 17(2): e0262891, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35130285

RESUMO

The ascomycete, Sclerotinia sclerotiorum, has a broad host range and causes yield loss in dicotyledonous crops world wide. Genomic diversity was determined in a population of 127 isolates obtained from individual canola (Brassica napus) fields in western Canada. Genotyping with 39 simple sequence repeat (SSR) markers revealed each isolate was a unique haplotype. Analysis of molecular variance showed 97% was due to isolate and 3% due to geographical location. Testing of mycelium compatibility among 133 isolates identified clones of mutually compatible isolates with 86-95% similar SSR haplotype, whereas incompatible isolates were highly diverse. In the Province of Manitoba, 61% of isolates were compatible forming clones and stings of pairwise compatible isolates not described before. In contrast, only 35% of isolates were compatible in Alberta without forming clones and strings, while 39% were compatible in Saskatchewan with a single clone, but no strings. These difference can be explained by wetter growing seasons and more susceptible crop species in Manitoba favouring frequent mycelium interaction and more life cycles over time, which might also explain similar differences observed in other geographical areas and host crops. Analysis of linkage disequilibrium rejected random recombination, consistent with a self-fertile fungus, restricted outcrossing due to mycelium incompatibility, and only a single annual opportunity for genomic recombination during meiosis in the ascospore stage between non-sister chromatids in the rare event nuclei from different isolates come together. More probable sources of genomic diversity is slippage during DNA replication and point mutation affecting single nucleotides that accumulate and likely increase mycelium incompatibility in a population over time. A phylogenetic tree based on SSR haplotype grouped isolates into 17 sub-populations. Aggressiveness was tested by inoculating one isolate from each sub-population onto B. napus lines with quantitative resistance. Analysis of variance was significant for isolate, line, and isolate by line interaction. These isolates represent the genomic and pathogenic diversity in western Canada, and are suitable for resistance screening in canola breeding programs.


Assuntos
Ascomicetos
19.
Methods Mol Biol ; 2443: 285-308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35037213

RESUMO

SynVisio and Accusyn ( genomevis.usask.ca ) are freely available web-based tools for visualizing genomic conservation that provide easy-to-access visualizations for researchers to interact with their datasets and change parameters in real time to carry out synteny exploration and analysis through multiple coordinated visual representations. The tools use standard file formats and outputs from existing synteny detection systems such as MCScanX or DAGChainer, and provide several features that are valuable for large-scale genomic analysis: a range of visualization scales from full genomes down to single collinearity blocks; single-level and multiple-level plots that enable the analysis of more than two genomic regions; annotation tracks that can be loaded using standard BedGraph files; several techniques for reducing visual clutter in visualizations; the ability to download high-quality images of the visualizations; and a snapshot panel for storing configurations of the interface for later revisitation.


Assuntos
Genômica , Software , Sintenia , Genoma , Genômica/métodos
20.
Front Plant Sci ; 13: 1044420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36605965

RESUMO

Jackfruit (Artocarpus heterophyllus Lam.) is the national fruit of Bangladesh and produces fruit in the summer season only. However, jackfruit is not commercially grown in Bangladesh because of an extremely high variation in fruit quality, short seasonal fruiting (June-August) and susceptibility to abiotic stresses. Conversely, a year-round high yielding (ca. 4-fold higher than the seasonal variety) jackfruit variety, BARI Kanthal-3 developed by the Bangladesh Agricultural Research Institute (BARI) derived from a wild accession found in Ramgarh of Chattogram Hiltracts of Bangladesh, provides fruits from September to June. This study aimed to generate a draft whole-genome sequence (WGS) of BARI Kanthal-3 to obtain molecular insights including genes associated with year-round fruiting trait of this important unique variety. The estimated genome size of BARI Kanthal-3 was 1.04-gigabase-pair (Gbp) with a heterozygosity rate of 1.62%. De novo assembly yielded a scaffolded 817.7 Mb genome while a reference-guided approach, yielded 843 Mb of genome sequence. The estimated GC content was 34.10%. Variant analysis revealed that BARI Kanthal-3 included 5.7 M (35%) and 10.4 M (65%) simple and heterozygous single nucleotide polymorphisms (SNPs), and about 90% of all these polymorphisms are in inter-genic regions. Through BUSCO assessment, 97.2% of the core genes were represented in the assembly with 1.3% and 1.5% either fragmented or missing, respectively. By comparing identified orthologous gene groups in BARI Kanthal-3 with five closely and one distantly related species of 10,092 common orthogroups were found across the genomes of the six species. The phylogenetic analysis of the shared orthogroups showed that A. heterophyllus was the closest species to BARI Kanthal-3 and orthogroups related to flowering time were found to be more highly prevalent in BARI Kanthal-3 compared to the other Arctocarpus spp. The findings of this study will help better understanding the evolution, domestication, phylogenetic relationships, year-round fruiting of this highly nutritious fruit crop as well as providing a resource for molecular breeding.

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