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1.
Pestic Biochem Physiol ; 202: 105921, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879297

RESUMO

The evolution of resistance to insecticides poses a significant threat to pest management programs. Understanding the molecular mechanisms underlying insecticide resistance is essential to design sustainable pest control and resistance management programs. The fall armyworm, Spodoptera frugiperda, is an important insect pest of many crops and has a remarkable ability to evolve resistance to insecticides. In this study, we employed bulk segregant analysis (BSA) combined with DNA and RNA sequencing to characterize the molecular basis of spinetoram resistance in S. frugiperda. Analysis of genomic data derived from spinetoram selected and unselected bulks and the spinetoram-resistant and susceptible parental strains led to the identification of a three-nucleotide deletion in the gene encoding the nicotinic acetylcholine receptor α6 subunit (nAChR α6). Transcriptome profiling identified the upregulation of few genes encoding detoxification enzymes associated with spinetoram resistance. Thus, spinetoram resistance in S. frugiperda appears to be mediated mainly by target site insensitivity with a minor role of detoxification enzymes. Our findings provide insight into the mechanisms underpinning resistance to spinetoram in S. frugiperda and will inform the development of strategies to control this highly damaging, globally distributed crop pest.


Assuntos
Resistência a Inseticidas , Inseticidas , Spodoptera , Animais , Spodoptera/genética , Spodoptera/efeitos dos fármacos , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Inseticidas/toxicidade , Perfilação da Expressão Gênica , Transcriptoma , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Macrolídeos
2.
J Appl Genet ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551768

RESUMO

Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies. Genomic DNA was target captured with a panel of 46 genes and libraries sequenced on Illumina platform. Analysis identified, reported pathogenic as well as novel pathogenic (n = 6) variants in 16 probands. Of the 10 HCM patients, candidate variants were identified in nine of them involving sarcomere genes (62%, MYBPC3, MYH6, MYH7, MYL3, TTN), Z-disc (10%, ACTN2, LDB3, NEXN,), desmosome (10%, DSG2, DSP, PKP2) cytoskeletal (4%, DTNA) and ion channel (10% RYR2). In four DCM patients, variants were identified in genes NEXN, LMNA and TTN. Three arrhythmogenic right ventricular cardiomyopathy (ARVD) patients carried mutations in desmosome genes. Rare TTN variants were identified in multiple patients. Targeted capture and sequencing resulted in identification of candidate variants in about 70% of the samples which will help in management of disease in affected individual as well as in screening and early diagnosis in asymptomatic family members. Amongst the analysed cases, 22% were inconclusive without any significant variant identified. Study illustrates the utility of next-generation multi-gene panel as a cost-effective genetic testing to screen all forms of primary cardiomyopathies.

3.
J West Afr Coll Surg ; 14(1): 113-117, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486652

RESUMO

Although gastrointestinal stromal tumours (GISTs) are encountered all along the gastrointestinal tract, duodenal GISTs are uncommon and account for <5% of the cases. A 45-year-old woman presented chiefly with anaemia and associated symptoms, whom on further evaluation was found to have a non-metastatic GIST in the distal duodenum sparing the pancreas and major vasculature. Patient was undertaken for segmental duodenectomy with the help of advanced bipolar energy device (tumour occupying D3-D4 with 1 cm proximal margin and 15 cm jejunum) preserving the pancreas and ampulla with end-to-end duodenojejunostomy with an uneventful postoperative course and clear margins on histopathology. Thus, the patient underwent a less morbid procedure with satisfactory oncological outcome and early resumption of activity. This highlights the need to conduct more trials to gather high level evidence in favour of conservative resection and its oncological adequacy and impact on overall survival and recurrence.

4.
Front Aging Neurosci ; 15: 1216052, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37539345

RESUMO

The purpose of this study was to compare the effects of music therapy (MT) and/or physical rehabilitation (PR) on cognitive and motor function in elderly Tunisian male and female patients with mild Alzheimer's disease (AD). Male patients (N: 16; age: 74.19 ± 4.27 years; weight: 76.71 ± 5.22 kg) and female patients (N: 12; age: 71.46 ± 3.36 years; weight: 67.47 ± 4.31 kg) with mild AD were randomly assigned into 4 groups including control group (Co), PR group participated in physical rehabilitation, MT group received music therapy and MT + PR received both music therapy and physical rehabilitation. Participants were required to engage in the study for four months with three 60-min sessions per week. We found all scores of cognitive (MMSE, ADAS-Cog Total and the ADAS-Cog Memory subscale) and motor functions (step length, walking speed, 6MVT and BBS score) evaluated were the greatest in MT + PR compared to the other groups. Our study also demonstrated that MT has a greater effect on cognitive function, while PR has a more pronounced effect on motor function. Changes in MMSE scores were significantly positively correlated in the PR, MT and MT + PR groups with improvements in all motor functions including step length (r = 0.77), walking speed (r = 0.73), 6MVT (r = 0.75) and BBS scores (r = 0.78) in AD patients. In conclusion, the combination of MT and PR seems to be an appropriate intervention approach that needs consideration as a treatment strategy for elderly male and female patients with mild AD.

5.
Insect Biochem Mol Biol ; 159: 103983, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380137

RESUMO

The tomato leafminer, Tuta absoluta, is an invasive crop pest that has evolved resistance to many of the insecticides used for its control. To facilitate the investigation of the underpinning mechanisms of resistance in this species we generated a contiguous genome assembly using long-read sequencing data. We leveraged this genomic resource to investigate the genetic basis of resistance to the diamide insecticide chlorantraniliprole in Spanish strains of T. absoluta that exhibit high levels of resistance to this insecticide. Transcriptomic analyses revealed that, in these strains, resistance is not associated with previously reported target-site mutations in the diamide target-site, the ryanodine receptor, but rather is associated with the marked overexpression (20- to >100-fold) of a gene encoding a UDP-glycosyltransferase (UGT). Functional expression of this UGT, UGT34A23, via ectopic expression in Drosophila melanogaster demonstrated that it confers strong and significant resistance in vivo. The genomic resources generated in this study provide a powerful resource for further research on T. absoluta. Our findings on the mechanisms underpinning resistance to chlorantraniliprole will inform the development of sustainable management strategies for this important pest.


Assuntos
Inseticidas , Lepidópteros , Mariposas , Solanum lycopersicum , Animais , Inseticidas/farmacologia , Diamida , Resistência a Inseticidas/genética , Drosophila melanogaster , Difosfato de Uridina
6.
Int J Biol Macromol ; 244: 125146, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37271267

RESUMO

Probiotic surface layer proteins (Slps) have multiple functions and bacterial adhesion to host cells is one of them. The precise role of Slps in cellular adhesion is not well understood due to its low native protein yield and self-aggregative nature. Here, we report the recombinant expression and purification of biologically active Slp of Lactobacillus helveticus NCDC 288 (SlpH) in high yield. SlpH is a highly basic protein (pI = 9.4), having a molecular weight of 45 kDa. Circular Dichroism showed a prevalence of beta-strands in SlpH structure and resistance to low pH. SlpH showed binding to human intestinal tissue, enteric Caco-2 cell line, and porcine gastric mucin, but not with fibronectin, collagen type IV and laminin. SlpH inhibited the binding of the enterotoxigenic E. coli by 70 % and 76 % and that of Salmonella Typhimurium SL1344 by 71 % and 75 % to enteric Caco-2 cell line in the exclusion and competition assays, respectively. The pathogen exclusion and competition activity and tolerance to harsh gastrointestinal conditions show the potential for developing SlpH as a prophylactic or therapeutic agent against enteric pathogens.


Assuntos
Lactobacillus helveticus , Probióticos , Animais , Humanos , Suínos , Proteínas de Membrana , Lactobacillus helveticus/genética , Escherichia coli , Células CACO-2 , Interações entre Hospedeiro e Microrganismos , Aderência Bacteriana , Probióticos/metabolismo
7.
Cureus ; 15(2): e34755, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36909061

RESUMO

Introduction Low-level laser therapy (LLLT) has a beneficial effect on pain relief and wound healing. This study aims at a clinical evaluation of early wound healing and a biochemical evaluation of inflammatory mediators in gingival crevicular fluid (GCF) following LLLT with an open flap debridement (OFD) in periodontal therapy. Material and methods This randomized controlled trial included 40 chronic periodontitis patients with bilateral attachment loss, pocket depths of 5 mm affecting at least two quadrants, and radiographic evidence of horizontal bone loss. 120 control sites were randomly selected to receive OFD, and contralateral 120 test sites received bio-stimulation with a diode laser (890 nm) after OFD. The wound healing index was recorded at the 1st and 2nd weeks, and clinical parameters such as the plaque index, gingival index, pocket probing depth, clinical attachment level, and GCF inflammatory mediators were evaluated at baseline, 3, and 6 months. Results From the start of the study to 6 months later, there was a statistically significant drop in plaque index, gingival index, probing pocket depth, and gain clinical attachment levels in both groups. However, when the two groups were compared, there were no significant differences at any time intervals. GCF inflammatory mediators tumor necrosis factor (TNF) alpha and matrix metalloproteinases (MMP-8) decrease, and osteoprotegerin (OPG) levels increase in both the test group and control group from baseline to 3 months and 6 months. In intergroup comparisons, there was a statistically significant reduction in the test group as compared to the control group at 6 months. There was a decline in gingival crevicular fluid - interleukin-6 (GCF IL-6) levels from baseline to 3 months and 6 months in both the groups but when analysed statistically, the results were not significant on intergroup and intragroup comparison at any time interval. The Landry Wound Healing Index values in the 1st and 2nd weeks were showing statistically significant improved healing in the test group as compared to the control group. There was significantly better wound healing at sites where a diode laser was used. Conclusion LLLT increases early wound healing after periodontal surgical procedures.

9.
Pathogens ; 12(1)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36678443

RESUMO

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm's excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in female and male ESPs, respectively, using this improved version, identifying a total of 795 ESPs (70% in both sexes, with the remaining sex-specific). Using functional databases (KEGG, GO and Interpro), common and sex-specific enriched functions were identified. Comparisons with the exclusively human-infective hookworm Necator americanus identified species-specific and conserved ESPs. This is the first study identifying ESPs from female and male A. ceylanicum. The findings provide a deeper understanding of hookworm protein functions that assure long-term host survival and facilitate future engineering of transgenic hookworms and analysis of regulatory elements mediating the high-level expression of ESPs. Furthermore, the findings expand the list of potential vaccine and diagnostic targets and identify biologics that can be explored for anti-inflammatory potential.

10.
J Pediatr Orthop ; 43(2): e144-e150, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607923

RESUMO

We have been treating children with Legg-Calvé-Perthes disease (LCPD) with a femoral varus osteotomy (PFVO) and weight relief till the disease evolves to the latter part of the stage of reconstitution (Stage IIIb). This entails weight relief for 18 to 24 months. We undertook this case-control study to test if a shorter period of weight relief would compromise the chance of retaining the spherical shape of the femoral head when the disease healed. Forty-one children diagnosed in the early stages of LCPD (Stages Ia, Ib, and IIa), were treated by PFVO and non-weight-bearing for a period of 6 months following surgery (6m group). Eighty-two children with LCPD matched for age, sex, and stage at surgery, who resumed weight-bearing only once they reached Stage IIIb, served as the control group (3b group). Both groups were followed up till the disease healed. The sphericity deviation score was calculated, and the height and width of the epiphysis were measured on the first radiograph designated as Stage IV. The median sphericity deviation score value at healing was 3 in the 3b group and 11 in the 6m group (P<0.001). The frequency of spherical heads was 76% in the 3b group and 49% in the 6m group (P<0.003). The Odds Ratio of the disease healing with an aspherical head in 6-month group was 3.05 (CI: 1.28 to 7.22) compared with the 3b group. The percentage increase in width of the femoral epiphysis at healing was greater in the 6 group (111.5±8.5% vs. 106.5±7.2%; P<0.001). The study confirms that containment by PFVO performed early in the course of LCPD combined with weight relief till the disease has evolved to Stage IIIb is likely to result in spherical hips in 75% of children. Reducing the period of weight relief to 6 months may yield significantly poorer results with only 49% spherical femoral heads.


Assuntos
Doença de Legg-Calve-Perthes , Criança , Humanos , Doença de Legg-Calve-Perthes/cirurgia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Estudos de Casos e Controles , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Fêmur , Radiografia
11.
Insect Biochem Mol Biol ; 153: 103896, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36587809

RESUMO

In some aphid species, intraspecific variation in body colour is caused by differential carotenoid content: whilst green aphids contain only yellow carotenoids (ß-, γ-, and ß,γ-carotenes), red aphids additionally possess red carotenoids (torulene and 3,4-didehydrolycopene). Unusually, within animals who typically obtain carotenoids from their diet, ancestral horizontal gene transfer of carotenoid biosynthetic genes from fungi (followed by gene duplication), have imbued aphids with the intrinsic gene repertoire necessary to biosynthesise carotenoids. In the pea aphid, Acyrthosiphon pisum a lycopene (phytoene) desaturase gene (Tor) underpins the red/green phenotype, with this locus present in heterozygous form in red individuals but absent in green aphids, resulting in them being unable to convert lycopene into the red compounds 3,4-didehydrolycopene and torulene. The green peach aphid, Myzus persicae, separated from the pea aphid for ≈45MY also exists as distinct colour variable morphs, with both red and green individuals present. Here, we examined genomic data for both red and green morphs of M. persicae and identified an enlarged (compared to A. pisum) repertoire of 16 carotenoid biosynthetic genes (11 carotenoid desaturases and five carotenoid cyclase/synthase genes). From these, we identify the homolog of A. pisum Tor (here called carotene desaturase 2 or CDE-2) and show through 3D modelling that this homolog can accommodate the torulene precursor lycopene and, through RNA knockdown feeding experiments, demonstrate that disabling CDE-2 expression in red M. persicae clones results in green-coloured offspring. Unlike in A. pisum, we show that functional CDE-2 is present in the genomes of both red and green aphids. However, expression differences between the two colour morphs (350-700 fold CDE-2 overexpression in red clones), potentially driven by variants identified in upstream putative regulatory elements, underpin this phenotype. Thus, whilst aphids have a common origin of their carotenoid biosynthetic pathway, two aphid species separated for over 40MY have evolved very different drivers of intraspecific colour variation.


Assuntos
Afídeos , Animais , Afídeos/fisiologia , Licopeno/metabolismo , Pigmentação/genética , Carotenoides/metabolismo
12.
J Pediatr Orthop B ; 32(1): 87-93, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36445353

RESUMO

This study was undertaken to evaluate the results of patella tendon shortening to correct patella alta in the context of surgery for the management of severe crouch gait. Our aim was to ascertain whether the corrected position of the patella and improvement of the power of the quadriceps were maintained for 4 years or more. Twenty older children (mean age: 14.2 years) with long-standing crouch gait secondary to cerebral diplegia underwent surgery to correct crouch gait that included the patellar tendon shortening. The technique for plicating the tendon differed for skeletally mature and immature patients. The length of the patellar tendon was measured by the Koshino Index. The strength of the quadriceps muscle was assessed by manual muscle testing and with a dynamometer and extensor lag, if present, was measured with a goniometer. In all 40 knees, the patella was brought to a more distal position and the position was maintained for a mean duration of 84 months (Koshino Index: preoperative 1.3 ± 0.10; 3-month postoperative 0.95 ± 0.05; final follow-up 0.95 ± 0.04). The results were the same for the techniques used for skeletally mature and immature patients. The power of the quadriceps improved [Medical Research Council (MRC) grade 3 to MRC grade 4] and the improvement was maintained. The technique of patella tendon shortening was effective in correcting patella alta and improving quadriceps power. The shortened patellar tendon did not stretch over the period of follow-up. Level of evidence: III.


Assuntos
Paralisia Cerebral , Criança , Humanos , Adolescente , Paralisia Cerebral/complicações , Paralisia Cerebral/cirurgia , Marcha
13.
Insect Biochem Mol Biol ; 152: 103890, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36496139

RESUMO

The Neotropical brown stink bug, Euschistus heros, is a major pest of soybean in South America. The importance of E. heros as a pest has grown significantly in recent times due to increases in its abundance and range, and the evolution of insecticide resistance. Recent work has begun to examine the genetic diversity, population structure, and genetic mechanisms of insecticide resistance in E. heros. However, to date, investigation of these topics has been hampered by a lack of genomic resources for this species. Here we address this need by assembling a high-quality draft genome for E. heros. We used a combination of short and long read sequencing to assemble an E. heros genome of 1.4 Gb comprising 906 contigs with a contig N50 of 3.5 MB. We leveraged this new genomic resource, in combination with genotyping by sequencing, to explore genetic diversity in populations of this species in Brazil and identify genetic loci in the genome which are under selection. Our genome-wide analyses, confirm that there are two populations of E. heros co-occurring in different geographical regions in Brazil, and that, in certain regions of the country these populations are hybridizing. We identify several regions of the genome as under selection, including markers associated with putative insecticide resistance genes. Taken together, the new genomic resources generated in this study will accelerate research into fundamental aspects of stinkbug biology and applied aspects relating to the sustainable control of a highly damaging crop pest.


Assuntos
Heterópteros , Inseticidas , Animais , Estudo de Associação Genômica Ampla , Heterópteros/genética , Brasil , Demografia
14.
Sci Total Environ ; 858(Pt 3): 160178, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379333

RESUMO

Sewage wastewater pollutes water and poses a public health issue but it could also prove useful in certain research domains. Sewage is a complex niche relevant for research concerning 'one-health', human health, pollution and antibiotic resistance. Indian gut microbiome is also understudied due to sampling constraints and sewage could be used to explore it. Ostensibly, Indian sewage needs to be studied and here, we performed a cross-sectional pan-India sewage sampling to generate the first comprehensive Indian sewage microbiome. Indian sewage showed predominance of Burkholderiaceae, Rhodocyclaceae, Veillonellaceae, Prevotellaceae, etc. and has high representation of gut microbes. The identified gut microbes have overrepresentation of Veillonellaceae, Rikenellaceae, Streptococcaceae, and Bacillaceae. Imputed metagenomics of sewage microbiome indicated dominance of transport, motility, peptidases, amino acid metabolism, and antibiotic resistance genes. Microbiome-disease associations drawn using simple decision tree and random forest analysis identified specific microbes as potential predictors of diabetes and obesity in a city. Altogether, we generated the first Indian sewage microbiome and our non-invasive, high-throughput workflow could be emulated for future research, wastewater-based epidemiology and designing policies concerning public health.


Assuntos
Metagenômica , Esgotos , Humanos , Estudos Transversais , Índia
15.
Probiotics Antimicrob Proteins ; 15(1): 44-62, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36357656

RESUMO

The growing consumer awareness towards healthy and safe food has reformed food processing strategies. Nowadays, food processors are aiming at natural, effective, safe, and low-cost substitutes for enhancing the shelf life of food products. Milk, besides being a rich source of nutrition for infants and adults, serves as a readily available source of precious functional peptides. Due to the existence of high genetic variability in milk proteins, there is a great possibility to get bioactive peptides with varied properties. Among other bioactive agents, milk-originated antimicrobial peptides (AMPs) are gaining interest as attractive and safe additive conferring extended shelf life to minimally processed foods. These peptides display broad-spectrum antagonistic activity against bacteria, fungi, viruses, and protozoans. Microbial proteolytic activity, extracellular peptidases, food-grade enzymes, and recombinant DNA technology application are among few strategies to tailor specific peptides from milk and enhance their production. These bioprotective agents have a promising future in addressing the global concern of food safety along with the possibility to be incorporated into the food matrix without compromising overall consumer acceptance. Additionally, in conformity to the current consumer demands, these AMPs also possess functional properties needed for value addition. This review attempts to present the basic properties, synthesis approaches, action mechanism, current status, and prospects of antimicrobial peptide application in food, dairy, and pharma industry along with their role in ensuring the safety and health of consumers.


Assuntos
Peptídeos Antimicrobianos , Proteínas do Leite , Leite , Animais , Humanos , Peptídeos Antimicrobianos/análise , Peptídeos Antimicrobianos/uso terapêutico , Bactérias , Leite/química , Proteínas do Leite/análise , Proteínas do Leite/uso terapêutico , Peptídeos/farmacologia , Peptídeos/química
16.
IEEE Sens J ; 22(19): 18437-18445, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36416744

RESUMO

The development of a cost-efficient device to rapidly detect pandemic viruses is paramount. Hence, an innovative and scalable synthesis of metal nanoparticles followed by its usage for rapid detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been reported in this work. The simple synthesis of metal nanoparticles utilizing tin as a solid-state reusable reducing agent is used for the SARS-CoV-2 ribonucleic acid (RNA) detection. Moreover, the solid-state reduction process occurs faster and leads to the enhanced formation of silver and gold nanoparticles (AuNPs) with voltage. By adding tin as a solid-state reducing agent with the precursor, the nanoparticles are formed within 30 s. This synthesis method can be easily scaled up for a commercially viable process to obtain different-sized metal nanoparticles. This is the first disclosure of the usage of tin as a reusable solid-state reducing agent for metal nanoparticle synthesis. An electronic device, consisting of AuNPs functionalized with a deoxyribonucleic acid (DNA)-based aptamer, can detect SARS-CoV-2 RNA in less than 5 min. With an increase in SARS-CoV-2 variants, such as Delta and Omicron, the detection device could be used for identifying the nucleic acids of the COVID-19 variants by modifying the aptamer sequence. The reported work overcomes the drawbacks of complex instrumentation, trained labor, and increased turnaround time.

17.
Microbiol Resour Announc ; 11(11): e0079322, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36250856

RESUMO

Two pasteurization-resistant strains, VHT1 and VHT2, of environmental, viable but nonculturable, pathogenic Vibrio parahaemolyticus were isolated from environmental oysters. Their whole-genome sequences were constructed. The genome sizes for VHT1 and VHT2 are 5.11 Mbp and 5.26 Mbp, respectively.

18.
Nat Commun ; 13(1): 5834, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192422

RESUMO

Streptomyces are our principal source of antibiotics, which they generate concomitant with a complex developmental transition from vegetative hyphae to spores. c-di-GMP acts as a linchpin in this transition by binding and regulating the key developmental regulators, BldD and WhiG. Here we show that c-di-GMP also binds the glycogen-debranching-enzyme, GlgX, uncovering a direct link between c-di-GMP and glycogen metabolism in bacteria. Further, we show c-di-GMP binding is required for GlgX activity. We describe structures of apo and c-di-GMP-bound GlgX and, strikingly, their comparison shows c-di-GMP induces long-range conformational changes, reorganizing the catalytic pocket to an active state. Glycogen is an important glucose storage compound that enables animals to cope with starvation and stress. Our in vivo studies reveal the important biological role of GlgX in Streptomyces glucose availability control. Overall, we identify a function of c-di-GMP in controlling energy storage metabolism in bacteria, which is widespread in Actinobacteria.


Assuntos
Regulação Bacteriana da Expressão Gênica , Streptomyces , Regulação Alostérica , Animais , Antibacterianos/metabolismo , Proteínas de Bactérias/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Sistemas do Segundo Mensageiro , Streptomyces/metabolismo
19.
Nat Prod Rep ; 39(9): 1876-1896, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-35997060

RESUMO

Covering: up to 2022With the emergence of large amounts of omics data, computational approaches for the identification of plant natural product biosynthetic pathways and their genetic regulation have become increasingly important. While genomes provide clues regarding functional associations between genes based on gene clustering, metabolome mining provides a foundational technology to chart natural product structural diversity in plants, and transcriptomics has been successfully used to identify new members of their biosynthetic pathways based on coexpression. Thus far, most approaches utilizing transcriptomics and metabolomics have been targeted towards specific pathways and use one type of omics data at a time. Recent technological advances now provide new opportunities for integration of multiple omics types and untargeted pathway discovery. Here, we review advances in plant biosynthetic pathway discovery using genomics, transcriptomics, and metabolomics, as well as recent efforts towards omics integration. We highlight how transcriptomics and metabolomics provide complementary information to link genes to metabolites, by associating temporal and spatial gene expression levels with metabolite abundance levels across samples, and by matching mass-spectral features to enzyme families. Furthermore, we suggest that elucidation of gene regulatory networks using time-series data may prove useful for efforts to unwire the complexities of biosynthetic pathway components based on regulatory interactions and events.


Assuntos
Produtos Biológicos , Vias Biossintéticas , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Genômica , Metaboloma , Metabolômica , Plantas/genética , Plantas/metabolismo
20.
J Pediatr Orthop ; 42(6): e570-e576, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35442929

RESUMO

BACKGROUND: Among a cohort of 402 children with Legg-Calvé-Perthes disease (LCPD), 32 children presented with sclerosis and severe collapse of the entire femoral epiphysis that closely resembled a discus.This study was undertaken to identify the characteristics of children with this form of a "discoid epiphysis," compare them with typical LCPD and ascertain the radiologic outcome of their hips when the disease healed. METHODS: Sequential radiographs of the children were studied to monitor disease evolution. Femoral epiphyseal extrusion was measured on the initial anteroposterior radiograph. Thirty-one of the 32 children were treated with a proximal femoral varus osteotomy and weight-bearing was deferred till the disease reached stage IIIb. The pattern of fragmentation of the epiphysis was noted and the Sphericity Deviation Score (SDS) was computed once the disease healed. RESULTS: The mean age of children with a discoid epiphysis was 6.81±1.57 years at onset of symptoms while that of children with the typical presentation was 7.54±1.64 years (P<0.017). Perfusion magnetic resonance imaging scans of three children with a discoid epiphysis done in stage Ib of the disease showed that over 95% of the epiphysis was avascular. Femoral head extrusion was frequently present on the initial radiographs (mean Reimer's migration index 27.08±8.7; range: 6.4 to 42.55).In operated children with a discoid epiphysis, the disease evolved typically with fragmentation of the epiphysis followed by reconstitution. The height of the epiphysis was never restored; when the disease healed the mean epiphyseal height was 51.31±10.44% of the normal contralateral epiphysis as compared with 82.46±11.24% in children with typical LCPD (P<0.001).The SDS at healing of operated children with a discoid epiphysis was 14.95±10.86 while the SDS for operated children without a discoid epiphysis was 9.77±11.7 (P<0.019). However, the SDS of children with typical onset LCPD who had Catterall IV involvement and Herring C collapse was 15.25±15.19 (P=0.49 NS). CONCLUSION: The outcome of treatment of children with a discoid epiphysis is comparable to that of children with typical onset LCPD with Catterall IV (whole-head involvement) and Herring C collapse of the lateral pillar. About a third of these children who undergo early surgical containment may have spherical heads when the disease heals.


Assuntos
Doença de Legg-Calve-Perthes , Criança , Pré-Escolar , Epífises/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Humanos , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/cirurgia , Osteotomia/métodos , Radiografia
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