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1.
Proc Natl Acad Sci U S A ; 119(48): e2119824119, 2022 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409897

RESUMO

Fatty acids are vital for the survival of eukaryotes, but when present in excess can have deleterious consequences. The AMP-activated protein kinase (AMPK) is an important regulator of multiple branches of metabolism. Studies in purified enzyme preparations and cultured cells have shown that AMPK is allosterically activated by small molecules as well as fatty acyl-CoAs through a mechanism involving Ser108 within the regulatory AMPK ß1 isoform. However, the in vivo physiological significance of this residue has not been evaluated. In the current study, we generated mice with a targeted germline knock-in (KI) mutation of AMPKß1 Ser108 to Ala (S108A-KI), which renders the site phospho-deficient. S108A-KI mice had reduced AMPK activity (50 to 75%) in the liver but not in the skeletal muscle. On a chow diet, S108A-KI mice had impairments in exogenous lipid-induced fatty acid oxidation. Studies in mice fed a high-fat diet found that S108A-KI mice had a tendency for greater glucose intolerance and elevated liver triglycerides. Consistent with increased liver triglycerides, livers of S108A-KI mice had reductions in mitochondrial content and respiration that were accompanied by enlarged mitochondria, suggestive of impairments in mitophagy. Subsequent studies in primary hepatocytes found that S108A-KI mice had reductions in palmitate- stimulated Cpt1a and Ppargc1a mRNA, ULK1 phosphorylation and autophagic/mitophagic flux. These data demonstrate an important physiological role of AMPKß1 Ser108 phosphorylation in promoting fatty acid oxidation, mitochondrial biogenesis and autophagy under conditions of high lipid availability. As both ketogenic diets and intermittent fasting increase circulating free fatty acid levels, AMPK activity, mitochondrial biogenesis, and mitophagy, these data suggest a potential unifying mechanism which may be important in mediating these effects.


Assuntos
Proteínas Quinases Ativadas por AMP , Ácidos Graxos , Camundongos , Animais , Fosforilação , Ácidos Graxos/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Mitocôndrias/metabolismo , Homeostase , Autofagia , Triglicerídeos/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(45): e2204993119, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36322765

RESUMO

Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.


Assuntos
Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus/genética , Infecções Estafilocócicas/epidemiologia , Austrália/epidemiologia , Antibacterianos/farmacologia , Paquistão , Infecções Comunitárias Adquiridas/epidemiologia , Testes de Sensibilidade Microbiana
3.
Plant Mol Biol ; 114(4): 83, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38972957

RESUMO

Consumer trends towards nutrient-rich foods are contributing to global increasing demand for tropical fruit. However, commercial cultivars in the breeding pipeline that are tailored to meet market demand are at risk of possessing reduced fruit flavour qualities. This stems from recurrent prioritised selection for superior agronomic traits and not fruit flavour, which may in turn reduce consumer satisfaction. There is realisation that fruit quality traits, inclusive of flavour, must be equally selected for; but currently, there are limited tools and resources available to select for fruit flavour traits, particularly in tropical fruit species. Although sugars, acids, and volatile organic compounds are known to define fruit flavour, the specific combinations of these, that result in defined consumer preferences, remain unknown for many tropical fruit species. To define and include fruit flavour preferences in selective breeding, it is vital to determine the metabolites that underpin them. Then, objective quantitative analysis may be implemented instead of solely relying on human sensory panels. This may lead to the development of selective genetic markers through integrated omics approaches that target biosynthetic pathways of flavour active compounds. In this review, we explore progress in the development of tools to be able to strategically define and select for consumer-preferred flavour profiles in the breeding of new cultivars of tropical fruit species.


Assuntos
Frutas , Melhoramento Vegetal , Frutas/genética , Frutas/metabolismo , Melhoramento Vegetal/métodos , Compostos Orgânicos Voláteis/metabolismo , Paladar , Metabolômica/métodos , Aromatizantes/metabolismo , Clima Tropical , Multiômica
4.
Phytopathology ; 114(1): 7-20, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37530477

RESUMO

Sugarcane (Saccharum hybrid) is an important cash crop grown in tropical and subtropical countries. Ratoon stunting disease (RSD), caused by a xylem-inhabiting bacterium, Leifsonia xyli subsp. xyli (Lxx) is one of the most economically significant diseases globally. RSD results in severe yield losses because its highly contagious nature and lack of visually identifiable symptoms make it harder to devise an effective management strategy. The efficacy of current management practices is hindered by implementation difficulties caused by lack of resources, high cost, and difficulties in monitoring. Rapid detection of the causal pathogen in vegetative planting material is crucial for sugarcane growers to manage this disease. Several microscopic, serological, and molecular-based methods have been developed and used for detecting the RSD pathogen. Although these methods have been used across the sugarcane industry worldwide to diagnose Lxx, some lack reliability or specificity, are expensive and time-consuming to apply, and most of all, are not suitable for on-farm diagnosis. In recent decades, there has been significant progress in the development of integrated isothermal amplification-based microdevices for accurate human and plant pathogen detection. There is a significant opportunity to develop a novel diagnostic method that integrates nanobiosensing with isothermal amplification within a microdevice format for accurate Lxx detection. In this review, we summarize (i) the historical background and current knowledge of sugarcane ratoon stunting disease, including some aspects related to transmission, pathosystem, and management practices; and (ii) the drawbacks of current diagnostic methods and the potential for application of advanced diagnostics to improve disease management.


Assuntos
Actinomycetales , Saccharum , Humanos , Saccharum/microbiologia , Reprodutibilidade dos Testes , Doenças das Plantas/microbiologia , Xilema/microbiologia
5.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474290

RESUMO

Commercial papaya varieties grown in Australia vary greatly in taste and aroma. Previous profiling has identified undesirable 'off tastes' in existing varieties, discouraging a portion of the population from consuming papayas. Our focus on enhancing preferred flavours led to an exploration of the genetic mechanisms and biosynthesis pathways that underlie these desired taste profiles. To identify genes associated with consumer-preferred flavours, we conducted whole RNA sequencing and de novo genome assembly on papaya varieties RB1 (known for its sweet flavour and floral aroma) and 1B (less favoured due to its bitter taste and musty aroma) at both ripe and unripe stages. In total, 180,368 transcripts were generated, and 118 transcripts related to flavours were differentially expressed between the two varieties at the ripe stage. Five genes (cpBGH3B, cpPFP, cpSUS, cpGES and cpLIS) were validated through qPCR and significantly differentially expressed. These genes are suggested to play key roles in sucrose metabolism and aromatic compound production pathways, holding promise for future selective breeding strategies. Further exploration will involve assessing their potential across broader germplasm and various growth environments.


Assuntos
Carica , Paladar , Carica/genética , Austrália , Percepção Gustatória , Aromatizantes
6.
Mol Biol Evol ; 39(3)2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35171290

RESUMO

Nanopore sequencing and phylodynamic modeling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic nanopore sequencing. Genome Res. 30(9):1354-1363) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (PNG; n = 159). Successive barcoded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low coverage (>5× to 10×) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (>90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth-death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and PNG.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Sequenciamento por Nanoporos , Bactérias/genética , Surtos de Doenças , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Staphylococcus aureus Resistente à Meticilina/genética , Filogenia , Staphylococcus aureus/genética
7.
Plant Biotechnol J ; 20(7): 1402-1416, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35395125

RESUMO

Salinity severely affects the yield of chickpea. Understanding the role of lncRNAs can shed light on chickpea salt tolerance mechanisms. However, because lncRNAs are encoded by multiple sites within the genome, their classification to reveal functional versatility at the transcriptional and the post-transcriptional levels is challenging. To address this, we deep sequenced 24 salt-challenged flower transcriptomes from two parental genotypes of a RIL population that significantly differ in salt tolerance ability. The transcriptomes for the first time included 12 polyadenylated and 12 non-polyadenylated RNA libraries to a sequencing depth of ~50 million reads. The ab initio transcriptome assembly comprised ~34 082 transcripts from three biological replicates of salt-tolerant (JG11) and salt-sensitive (ICCV2) flowers. A total of 9419 lncRNAs responding to salt stress were identified, 2345 of which were novel lncRNAs specific to chickpea. The expression of poly(A+) lncRNAs and naturally antisense transcribed RNAs suggest their role in post-transcriptional modification and gene silencing. Notably, 178 differentially expressed lncRNAs were induced in the tolerant genotype but repressed in the sensitive genotype. Co-expression network analysis revealed that the induced lncRNAs interacted with the FLOWERING LOCUS (FLC), chromatin remodelling and DNA methylation genes, thus inducing flowering during salt stress. Furthermore, 26 lncRNAs showed homology with reported lncRNAs such as COOLAIR, IPS1 and AT4, thus confirming the role of chickpea lncRNAs in controlling flowering time as a crucial salt tolerance mechanism in tolerant chickpea genotype. These robust set of differentially expressed lncRNAs provide a deeper insight into the regulatory mechanisms controlled by lncRNAs under salt stress.


Assuntos
Cicer , RNA Longo não Codificante , Cicer/genética , Cicer/metabolismo , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transcriptoma/genética
8.
Ophthalmic Plast Reconstr Surg ; 38(3): e72-e75, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34873125

RESUMO

Paraneoplastic extraocular muscle enlargement has been reported in a small number of patients with cancers including breast or lymphoma, usually presenting with bilateral multiple muscle involvement. Such myositis may be autoimmune. Furthermore, orbital inflammation is a recognized complication of immune-modulation therapy used to treat melanoma, such as ipilimumab. Extraorbital myositis has been described in myeloma, and polymyositis in melanoma. We present a case of bilateral, asymmetrical extraocular muscle enlargement with spontaneous resolution in a patient with simultaneous new diagnoses of metastatic malignant melanoma and multiple myeloma. A similar episode 7 months before diagnosis also resolved spontaneously. The authors believe this to be the first reported case of paraneoplastic orbital myositis associated with multiple myeloma or untreated malignant melanoma.


Assuntos
Melanoma , Mieloma Múltiplo , Miosite , Miosite Orbital , Humanos , Melanoma/complicações , Melanoma/diagnóstico , Miosite/diagnóstico , Miosite/etiologia , Miosite Orbital/diagnóstico , Miosite Orbital/etiologia , Neoplasias Cutâneas , Melanoma Maligno Cutâneo
9.
Int J Mol Sci ; 23(11)2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35682992

RESUMO

Inconsistency in flavour is one of the major challenges to the Australian papaya industry. However, objectively measurable standards of the compound profiles that provide preferable taste and aroma, together with consumer acceptability, have not been set. In this study, three red-flesh papayas (i.e., 'RB1', 'RB4', and 'Skybury') and two yellow-flesh papayas (i.e., '1B' and 'H13') were presented to a trained sensory panel and a consumer panel to assess sensory profiles and liking. The papaya samples were also examined for sugar components, total soluble solids, and 14 selected volatile compounds. Additionally, the expression patterns of 10 genes related to sweetness and volatile metabolism were assessed. In general, red papaya varieties had higher sugar content and tasted sweeter than yellow varieties, while yellow varieties had higher concentrations of citrus floral aroma volatiles and higher aroma intensity. Higher concentrations of glucose, linalool oxide, and terpinolene were significantly associated with decreased consumer liking. Significant differences were observed in the expression profiles of all the genes assessed among the selected papaya varieties. Of these, cpGPT2 and cpBGLU31 were positively correlated to glucose production and were expressed significantly higher in '1B' than in 'RB1' or 'Skybury'. These findings will assist in the strategic selective breeding for papaya to better match consumer and, hence, market demand.


Assuntos
Carica , Austrália , Carboidratos/análise , Carica/química , Carica/genética , Aromatizantes/metabolismo , Frutas/metabolismo , Glucose/metabolismo , Açúcares/metabolismo , Paladar , Verduras
10.
J Integr Plant Biol ; 64(11): 2187-2198, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36040241

RESUMO

One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing (SIGS). In SIGS, small interfering RNA (siRNA) or double-stranded RNA (dsRNA) targeting essential or virulence-related pathogen genes are exogenously applied to plants and postharvest products to trigger RNA interference (RNAi) of the targeted genes, inhibiting fungal growth and disease. However, SIGS is limited by the unstable nature of RNA under environmental conditions. The use of layered double hydroxide or clay particles as carriers to deliver biologically active dsRNA, a formulation termed BioClay™, can enhance RNA durability on plants, prolonging its activity against pathogens. Here, we demonstrate that dsRNA delivered as BioClay can prolong protection against Botrytis cinerea, a major plant fungal pathogen, on tomato leaves and fruit and on mature chickpea plants. BioClay increased the protection window from 1 to 3 weeks on tomato leaves and from 5 to 10 days on tomato fruits, when compared with naked dsRNA. In flowering chickpea plants, BioClay provided prolonged protection for up to 4 weeks, covering the critical period of poding, whereas naked dsRNA provided limited protection. This research represents a major step forward for the adoption of SIGS as an eco-friendly alternative to traditional fungicides.


Assuntos
Proteção de Cultivos , Solanum lycopersicum , Interferência de RNA , Botrytis , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , RNA de Cadeia Dupla/genética , RNA Interferente Pequeno/genética , Solanum lycopersicum/genética , Plantas/genética
11.
Orbit ; 41(3): 315-320, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33645420

RESUMO

BACKGROUND/AIMS: To explore differences in clinical presentations and outcomes between patients with biopsy-proven orbital lymphoma and orbital inflammatory disease. METHODS: Clinical records of all patients who underwent orbital biopsy at Bristol Eye Hospital during a 10-year period were reviewed. Comparisons were made between patients diagnosed with orbital lymphoma and orbital inflammatory disease (OID). RESULTS: 35 patients were diagnosed with orbital lymphoma, undergoing 40 biopsies over the 10-year period studied. 62 patients had OID, undergoing 66 biopsies. Sub-analysis identified six patients with sarcoidosis, four with granulomatosis polyangiitis (GPA), eight with IgG4-related orbital disease, and 44 with idiopathic orbital inflammation (IOI). Patients with sarcoidosis and IOI were statistically younger at presentation than those with lymphoma, with means of 44 and 52 years, respectively, compared with 71 years. Lid swelling/puffiness was more common in OID than lymphoma. More patients with lymphoma lost vision during follow-up than those with OID. CONCLUSIONS: Although younger age of presentation and presence of lid swelling are more likely to indicate orbital inflammation than orbital lymphoma, orbital biopsy remains the gold standard to distinguish these two entities. In the case of orbital inflammation, identification of a specific diagnosis allows appropriate ongoing referral and investigations for potential systemic involvement and helps guide immunosuppressive treatment.


Assuntos
Linfoma , Doenças Orbitárias , Sarcoidose , Humanos , Inflamação/diagnóstico , Linfoma/diagnóstico , Linfoma/patologia , Linfoma/terapia , Órbita/patologia , Doenças Orbitárias/patologia , Neoplasias Orbitárias , Estudos Retrospectivos , Sarcoidose/patologia , Centros de Atenção Terciária
12.
Orbit ; 41(4): 517-521, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33682595

RESUMO

We report a case of a 17-year-old female who presented with orbital cellulitis and meningeal involvement secondary to severe paranasal sinusitis with positive blood culture for Fusobacterium necrophorum. The patient recovered after a 2-month course of systemic antibiotics and functional endoscopic sinus surgery.Fusobacterium necrophorum-induced orbital cellulitis is a rare entity, with only 5 previous cases reported in the literature, which are reviewed here as well. This review reveals that Fusobacterium necrophorum is an aggressive pathogen in orbital cellulitis and therefore we suggest that affected patients may require a correspondingly aggressive medical management. Furthermore, we advise additional workup to rule out Lemierre's syndrome, a severe complication of Fusobacterium necrophorum infection, including transthoracic echocardiogram, chest radiograph, upper extremities' venous duplex and magnetic resonance venography.


Assuntos
Síndrome de Lemierre , Celulite Orbitária , Adolescente , Antibacterianos/uso terapêutico , Feminino , Fusobacterium necrophorum , Humanos , Síndrome de Lemierre/diagnóstico por imagem , Síndrome de Lemierre/tratamento farmacológico , Imageamento por Ressonância Magnética , Celulite Orbitária/diagnóstico por imagem , Celulite Orbitária/tratamento farmacológico
13.
Orbit ; 41(5): 547-550, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34334084

RESUMO

PURPOSE: To determine whether the long-term success of ptosis surgery is influenced by the use of absorbable or non-absorbable sutures to advance the levator aponeurosis onto the tarsal plate. METHODS: Multi-centre retrospective comparative study of re-operation rates in primary anterior approach ptosis surgery using absorbable polyglactin sutures (Vicryl) and non-absorbable polyester sutures (Ethibond). The Medisoft audit tool was used to identify all patients who underwent primary ptosis surgery for aponeurotic ptosis, performed by five oculoplastic consultants within a 7-year period, across two NHS Ophthalmology departments. The electronic patient records were reviewed for each patient. Basic demographics, suture material, and post-operative complications were recorded. All patients requiring repeat surgery between the study dates and the present day were recorded, allowing a minimum postoperative period of 3 years and 10 months. Re-operation rates in surgery using absorbable Vicryl sutures and non-absorbable Ethibond sutures were compared using Fisher's exact test. RESULTS: Four hundred and fifty-five operations in 330 patients were performed within the study period that met the inclusion and exclusion criteria. Fifty-seven percent of the patients were female, with an average age of 68.8 years. One hundred and sixty-nine operations in 128 patients were performed using absorbable Vicryl sutures. Of these, 22 (13.0%) required repeat operations. Two hundred and eighty-six operations in 202 patients were performed using non-absorbable Ethibond sutures. Of these, 17 (5.9%) required repeat operations. The two-tailed P-value was 0.0143. CONCLUSION: The use of non-absorbable Ethibond sutures to advance the levator aponeurosis onto the tarsal plate in primary ptosis surgery is associated with improved long-term success and reduced need for secondary surgery.


Assuntos
Blefaroptose , Poliglactina 910 , Idoso , Blefaroptose/etiologia , Blefaroptose/cirurgia , Pálpebras/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Suturas/efeitos adversos
14.
Clin Infect Dis ; 73(8): 1492-1499, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34043768

RESUMO

BACKGROUND: Between 2008 and 2018, persons granted asylum (asylees) increased by 168% in the United States. Asylees are eligible for many of the same domestic benefits as refugees under the US Refugee Admissions Program (USRAP), including health-related benefits such as the domestic medical examination. However, little is known about the health of asylees to guide clinical practice. METHODS: We conducted a retrospective cross-sectional analysis of domestic medical examination data from 9 US sites from 2014 to 2016. We describe and compare demographics and prevalence of several infectious diseases such as latent tuberculosis infection (LTBI), hepatitis B and C virus (HBV, HCV), and select sexually transmitted infections and parasites by refugee or asylee visa status. RESULTS: The leading nationalities for all asylees were China (24%) and Iraq (10%), while the leading nationalities for refugees were Burma (24%) and Iraq (19 %). Approximately 15% of asylees were diagnosed with LTBI, and 52% of asylee adults were susceptible to HBV infection. Prevalence of LTBI (prevalence ratio [PR] = 0.8), hepatitis B (0.7), hepatitis C (0.5), and Strongyloides (0.5) infections were significantly lower among asylees than refugees. Prevalence of other reported conditions did not differ by visa status. CONCLUSIONS: Compared to refugees, asylees included in our dataset were less likely to be infected with some infectious diseases but had similar prevalence of other reported conditions. The Centers for Disease Control and Prevention's Guidance for the US Domestic Medical Examination for Newly Arrived Refugees can also assist clinicians in the care of asylees during the routine domestic medical examination.


Assuntos
Tuberculose Latente , Refugiados , Adulto , Estudos Transversais , Humanos , Programas de Rastreamento , Estudos Retrospectivos , Estados Unidos/epidemiologia
15.
Br J Nutr ; : 1-18, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505561

RESUMO

Food manufacturers are under increasing pressure to limit the amount of free sugars in their products. Many have reformulated products to replace sucrose, glucose and fructose with alternative sweeteners, but some of these have been associated with additional health concerns. Rare sugars are 'monosaccharides and their derivatives that hardly exist in nature', and there is increasing evidence that they could have health benefits. This review aimed to scope the existing literature in order to identify the most commonly researched rare sugars, to ascertain their proposed health benefits, mechanisms of action and potential uses and to highlight knowledge gaps. A process of iterative database searching identified fifty-five relevant articles. The reported effects of rare sugars were noted, along with details of the research methodologies conducted. Our results indicated that the most common rare sugars investigated are d-psicose and d-tagatose, with the potential health benefits divided into three topics: glycaemic control, body composition and CVD. All the rare sugars investigated have the potential to suppress postprandial elevation of blood glucose and improve glycaemic control in both human and animal models. Some animal studies have suggested that certain rare sugars may also improve lipid profiles, alter the gut microbiome and reduce pro-inflammatory cytokine expression. The present review demonstrates that rare sugars could play a role in reducing the development of obesity, type 2 diabetes and/or CVD. However, understanding of the mechanisms by which rare sugars may exert their effects is limited, and their effectiveness when used in reformulated products is unknown.

16.
Biochem J ; 477(12): 2347-2361, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32510137

RESUMO

Sodium-glucose cotransporter 2 inhibitors such as canagliflozin lower blood glucose and reduce cardiovascular events in people with type 2 diabetes through mechanisms that are not fully understood. Canagliflozin has been shown to increase the activity of the AMP-activated protein kinase (AMPK), a metabolic energy sensor important for increasing fatty acid oxidation and energy expenditure and suppressing lipogenesis and inflammation, but whether AMPK activation is important for mediating some of the beneficial metabolic effects of canagliflozin has not been determined. We, therefore, evaluated the effects of canagliflozin in female ApoE-/- and ApoE-/-AMPK ß1-/- mice fed a western diet. Canagliflozin increased fatty acid oxidation and energy expenditure and lowered adiposity, blood glucose and the respiratory exchange ratio independently of AMPK ß1. Canagliflozin also suppressed liver lipid synthesis and the expression of ATP-citrate lyase, acetyl-CoA carboxylase and sterol response element-binding protein 1c independently of AMPK ß1. Canagliflozin lowered circulating IL-1ß and studies in bone marrow-derived macrophages indicated that in contrast with the metabolic adaptations, this effect required AMPK ß1. Canagliflozin had no effect on the size of atherosclerotic plaques in either ApoE-/- and ApoE-/-AMPK ß1-/- mice. Future studies investigating whether reductions in liver lipid synthesis and macrophage IL-1ß are important for the cardioprotective effects of canagliflozin warrant further investigation.


Assuntos
Apolipoproteínas E/fisiologia , Canagliflozina/farmacologia , Interleucina-1beta/fisiologia , Lipogênese , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Metabolismo Energético , Feminino , Inflamação/metabolismo , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout para ApoE , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia
17.
PLoS Med ; 17(3): e1003065, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32231391

RESUMO

BACKGROUND: Refugees and other select visa holders are recommended to receive a domestic medical examination within 90 days after arrival to the United States. Limited data have been published on the coverage of screenings offered during this examination across multiple resettlement states, preventing evaluation of this voluntary program's potential impact on postarrival refugee health. This analysis sought to calculate and compare screening proportions among refugees and other eligible populations to assess the domestic medical examination's impact on screening coverage resulting from this examination. METHODS AND FINDINGS: We conducted a cross-sectional analysis to summarize and compare domestic medical examination data from January 2014 to December 2016 from persons receiving a domestic medical examination in seven states (California, Colorado, Minnesota, New York, Kentucky, Illinois, and Texas); one county (Marion County, Indiana); and one academic medical center in Philadelphia, Pennsylvania. We analyzed screening coverage by sex, age, nationality, and country of last residence of persons and compared the proportions of persons receiving recommended screenings by those characteristics. We received data on disease screenings for 105,541 individuals who received a domestic medical examination; 47% were female and 51.5% were between the ages of 18 and 44. The proportions of people undergoing screening tests for infectious diseases were high, including for tuberculosis (91.6% screened), hepatitis B (95.8% screened), and human immunodeficiency virus (HIV; 80.3% screened). Screening rates for other health conditions were lower, including mental health (36.8% screened). The main limitation of our analysis was reliance on data that were collected primarily for programmatic rather than surveillance purposes. CONCLUSIONS: In this analysis, we observed high rates of screening coverage for tuberculosis, hepatitis B, and HIV during the domestic medical examination and lower screening coverage for mental health. This analysis provided evidence that the domestic medical examination is an opportunity to ensure newly arrived refugees and other eligible populations receive recommended health screenings and are connected to the US healthcare system. We also identified knowledge gaps on how screenings are conducted for some conditions, notably mental health, identifying directions for future research.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Refugiados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
18.
PLoS Med ; 17(3): e1003083, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32231361

RESUMO

BACKGROUND: Since 2008, the United States has issued between 2,000 and 19,000 Special Immigrant Visas (SIV) annually, with the majority issued to applicants from Iraq and Afghanistan. SIV holders (SIVH) are applicants who were employed by, or on behalf of, the US government or the US military. There is limited information about health conditions in SIV populations to help guide US clinicians caring for SIVH. Thus, we sought to describe health characteristics of recently arrived SIVH from Iraq and Afghanistan who were seen for domestic medical examinations. METHODS AND FINDINGS: This cross-sectional analysis included data from Iraqi and Afghan SIVH who received a domestic medical examination from January 2014 to December 2016. Data were gathered from state refugee health programs in seven states (California, Colorado, Illinois, Kentucky, Minnesota, New York, and Texas), one county, and one academic medical center and included 6,124 adults and 4,814 children. Data were collected for communicable diseases commonly screened for during the exam, including tuberculosis (TB), hepatitis B, hepatitis C, malaria, strongyloidiasis, schistosomiasis, other intestinal parasites, syphilis, gonorrhea, chlamydia, and human immunodeficiency virus, as well as elevated blood lead levels (EBLL). We investigated the frequency and proportion of diseases and whether there were any differences in selected disease prevalence in SIVH from Iraq compared to SIVH from Afghanistan. A majority of SIV adults were male (Iraqi 54.0%, Afghan 58.6%) and aged 18-44 (Iraqi 86.0%, Afghan 97.7%). More SIV children were male (Iraqi 56.2%, Afghan 52.2%) and aged 6-17 (Iraqi 50.2%, Afghan 40.7%). The average age of adults was 29.7 years, and the average age for children was 5.6 years. Among SIV adults, 14.4% were diagnosed with latent tuberculosis infection (LTBI), 63.5% were susceptible to hepatitis B virus (HBV) infection, and 31.0% had at least one intestinal parasite. Afghan adults were more likely to have LTBI (prevalence ratio [PR]: 2.0; 95% confidence interval [CI] 1.5-2.7) and to be infected with HBV (PR: 4.6; 95% CI 3.6-6.0) than Iraqi adults. Among SIV children, 26.7% were susceptible to HBV infection, 22.1% had at least one intestinal parasite, and 50.1% had EBLL (≥5 mcg/dL). Afghan children were more likely to have a pathogenic intestinal parasite (PR: 2.7; 95% CI 2.4-3.2) and EBLL (PR: 2.0; 95% CI 1.5-2.5) than Iraqi children. Limitations of the analysis included lack of uniform health screening data collection across all nine sites and possible misclassification by clinicians of Iraqi and Afghan SIVH as Iraqi and Afghan refugees, respectively. CONCLUSION: In this analysis, we observed that 14% of SIV adults had LTBI, 27% of SIVH had at least one intestinal parasite, and about half of SIV children had EBLL. Most adults were susceptible to HBV. In general, prevalence of infection was higher for most conditions among Afghan SIVH compared to Iraqi SIVH. The Centers for Disease Control and Prevention (CDC) Guidelines for the US Domestic Medical Examination for Newly Arriving Refugees can assist state public health departments and clinicians in the care of SIVH during the domestic medical examination. Future analyses can explore other aspects of health among resettled SIV populations, including noncommunicable diseases and vaccination coverage.


Assuntos
Emigrantes e Imigrantes/estatística & dados numéricos , Nível de Saúde , Programas de Rastreamento , Refugiados/estatística & dados numéricos , Adolescente , Adulto , Afeganistão/etnologia , Idoso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Iraque/etnologia , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
19.
Int J Mol Sci ; 21(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150870

RESUMO

Drought adversely affects crop production across the globe. The root system immensely contributes to water management and the adaptability of plants to drought stress. In this study, drought-induced phenotypic and transcriptomic responses of two contrasting chickpea (Cicer arietinum L.) genotypes were compared at the vegetative, reproductive transition, and reproductive stages. At the vegetative stage, drought-tolerant genotype maintained higher root biomass, length, and surface area under drought stress as compared to sensitive genotype. However, at the reproductive stage, root length and surface area of tolerant genotype was lower but displayed higher root diameter than sensitive genotype. The shoot biomass of tolerant genotype was overall higher than the sensitive genotype under drought stress. RNA-seq analysis identified genotype- and developmental-stage specific differentially expressed genes (DEGs) in response to drought stress. At the vegetative stage, a total of 2161 and 1873 DEGs, and at reproductive stage 4109 and 3772 DEGs, were identified in the tolerant and sensitive genotypes, respectively. Gene ontology (GO) analysis revealed enrichment of biological categories related to cellular process, metabolic process, response to stimulus, response to abiotic stress, and response to hormones. Interestingly, the expression of stress-responsive transcription factors, kinases, ROS signaling and scavenging, transporters, root nodulation, and oxylipin biosynthesis genes were robustly upregulated in the tolerant genotype, possibly contributing to drought adaptation. Furthermore, activation/repression of hormone signaling and biosynthesis genes was observed. Overall, this study sheds new insights on drought tolerance mechanisms operating in roots with broader implications for chickpea improvement.


Assuntos
Adaptação Fisiológica , Cicer/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Raízes de Plantas/genética , Estresse Fisiológico , Transcriptoma , Cicer/fisiologia , Biologia Computacional , Secas , Perfilação da Expressão Gênica , Raízes de Plantas/fisiologia
20.
Energy Policy ; 147: 111902, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32958976

RESUMO

This paper explores the trends, step changes and innovations that could impact the integration of renewable energy into electricity systems, explores interventions that may be required, and identifies key areas for policy makers to consider. A Delphi approach is used to collect, synthesise, and seek consensus across expert viewpoints. Over sixty experts across a range of geographies including the US, Europe, New-Zealand, Australia, Africa, India and China participated. They identified 26 trends, 20 step changes, and 26 innovations that could lead to major shifts in the design, operation, or management of electricity systems. Findings suggest that key challenges are not technological. Instead they are with delivering an aligned vision, supported by institutional structures, to incentivise, facilitate, and de-risk the delivery of a completely different type of energy system. There is a clear role for government and policy to provide a future energy vision and steer on strategic issues to deliver it; to create space for new actors and business models aligned with this vision; and to create an environment where research, development, demonstration and deployment can promote technologies, system integration and business model innovation at a rate commensurate with delivering net-zero electricity systems.

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