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1.
Environ Microbiol ; 26(3): e16600, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38482770

RESUMO

Microbial community structure and function were assessed in the organic and upper mineral soil across a ~4000-year dune-based chronosequence at Big Bay, New Zealand, where total P declined and the proportional contribution of organic soil in the profile increased with time. We hypothesized that the organic and mineral soils would show divergent community evolution over time with a greater dependency on the functionality of phosphatase genes in the organic soil layer as it developed. The structure of bacterial, fungal, and phosphatase-harbouring communities was examined in both horizons across 3 dunes using amplicon sequencing, network analysis, and qPCR. The soils showed a decline in pH and total phosphorus (P) over time with an increase in phosphatase activity. The organic horizon had a wider diversity of Class A (phoN/phoC) and phoD-harbouring communities and a more complex microbiome, with hub taxa that correlated with P. Bacterial diversity declined in both horizons over time, with enrichment of Planctomycetes and Acidobacteria. More complex fungal communities were evident in the youngest dune, transitioning to a dominance of Ascomycota in both soil horizons. Higher phosphatase activity in older dunes was driven by less diverse P-mineralizing communities, especially in the organic horizon.


Assuntos
Microbiota , Solo , Solo/química , Fósforo/análise , Floresta Úmida , Bactérias/genética , Microbiota/genética , Minerais , Monoéster Fosfórico Hidrolases/genética , Microbiologia do Solo
2.
Br J Cancer ; 128(5): 896-906, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36526674

RESUMO

CONTEXT: Many cancer patients who initially respond to chemotherapy eventually develop chemoresistance, and to address this, we previously conducted a RNAi screen to identify genes contributing to resistance. One of the hits from the screen was branched-chain α-keto acid dehydrogenase kinase (BCKDK). BCKDK controls the metabolism of branched-chain amino acids (BCAAs) through phosphorylation and inactivation of the branched-chain α-keto acid dehydrogenase complex (BCKDH), thereby inhibiting catabolism of BCAAs. METHODS: We measured the impact on paclitaxel sensitivity of inhibiting BCKDK in ovarian and breast cancer cell lines. RESULTS: Inhibition of BCKDK using siRNA or two chemical inhibitors (BCKDKi) was synergistic with paclitaxel in both breast and ovarian cancer cells. BCKDKi reduced levels of BCAA and the addition of exogenous BCAA suppressed this synergy. BCKDKi inactivated the mTORC1-Aurora pathway, allowing cells to overcame M-phase arrest induced by paclitaxel. In some cases, cells almost completed cytokinesis, then reverted to a single cell, resulting in multinucleate cells. CONCLUSION: BCKDK is an attractive target to augment the sensitivity of cancer cells to paclitaxel.


Assuntos
Neoplasias da Mama , Paclitaxel , Humanos , Feminino , Proteínas Quinases/genética , Fosforilação
3.
J Therm Biol ; 111: 103399, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36585074

RESUMO

OBJECTIVES: This study aimed to examine the impact of extreme heat exposure frequency on inflammation and well-being in UK Fire Service personnel. METHODS: 136 Fire personnel and 14 controls (CON) were recruited [92 Firefighters (FF), 44 Breathing Apparatus Instructors (BAI)]. BAI were split into low (LBAI; ≤15 exposures per month) and high (HBAI; ≥20 exposures per month) categories. Measures of inflammation, mood and fatigue were collected at 0, 3 and 6 month times points. These variables were analysed for differences between groups and association with frequency of exposure. RESULTS: HBAI exhibited raised IL-1ß, IL-6, IL-10, IgE and lower IgM (p < 0.05). In addition, IL-1ß, IL-6, IL-10 and IgM were associated with monthly exposure number, with exposures accounting for 15.4% of the variance in IL-6, 11.8% of IL-1ß and 25.2% of IL-10. No differences in mood or fatigue were reported (p > 0.05). CONCLUSION: High exposure firefighting consistently causes systemic inflammation without perceptual recognition of potential health risks.


Assuntos
Bombeiros , Exposição Ocupacional , Humanos , Interleucina-10 , Interleucina-6 , Inflamação/etiologia , Fadiga , Imunoglobulina M , Exposição Ocupacional/efeitos adversos
4.
Nurs Crit Care ; 28(1): 80-88, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35561020

RESUMO

BACKGROUND: The COVID-19 pandemic has been associated with an unprecedented number of critical care survivors. Their experiences through illness and recovery are likely to be complex, but little is known about how best to support them. AIM: This study aimed to explore experiences of illness and recovery from the perspective of survivors, their relatives and professionals involved in their care. STUDY DESIGN: In-depth qualitative interviews were conducted with three stakeholder groups during the first wave of the pandemic. A total of 23 participants (12 professionals, 6 survivors and 5 relatives) were recruited from 5 acute hospitals in England and interviewed by telephone or video call. Data analysis followed the principles of Reflexive Thematic Analysis. FINDINGS: Three themes were generated from their interview data: (1) Deteriorating fast-a downhill journey from symptom onset to critical care; (2) Facing a new virus in a hospital-a remote place; and (3) Returning home as a survivor, maintaining normality and recovering slowly. CONCLUSIONS: Our findings highlight challenges in accessing care and communication between patients, hospital staff and relatives. Following hospital discharge, patients adopted a reframed 'survivor identity' to cope with their experience of illness and slow recovery process. The concept of survivorship in this patient group may be beneficial to promote and explore further. RELEVANCE TO CLINICAL PRACTICE: All efforts should be made to continue to improve communication between patients, relatives and health professionals during critical care admissions, particularly while hospital visits are restricted. Adapting to life after critical illness may be more challenging while health services are restricted by the impacts of the pandemic. It may be beneficial to promote the concept of survivorship, following admission to critical care due to severe COVID-19.


Assuntos
COVID-19 , Cuidadores , Humanos , Pandemias , Pesquisa Qualitativa , Pessoal de Saúde
5.
Plant Physiol ; 187(4): 2279-2295, 2021 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-34618027

RESUMO

Certain soil microorganisms can improve plant growth, and practices that encourage their proliferation around the roots can boost production and reduce reliance on agrochemicals. The beneficial effects of the microbial inoculants currently used in agriculture are inconsistent or short-lived because their persistence in soil and on roots is often poor. A complementary approach could use root exudates to recruit beneficial microbes directly from the soil and encourage inoculant proliferation. However, it is unclear whether the release of common organic metabolites can alter the root microbiome in a consistent manner and if so, how those changes vary throughout the whole root system. In this study, we altered the expression of transporters from the ALUMINUM-ACTIVATED MALATE TRANSPORTER and the MULTIDRUG AND TOXIC COMPOUND EXTRUSION families in rice (Oryza sativa L.) and wheat (Triticum aestivum L.) and tested how the subsequent release of their substrates (simple organic anions, including malate, citrate, and γ-amino butyric acid) from root apices affected the root microbiomes. We demonstrate that these exudate compounds, separately and in combination, significantly altered microbiome composition throughout the root system. However, the root type (seminal or nodal), position along the roots (apex or base), and soil type had a greater influence on microbiome structure than the exudates. These results reveal that the root microbiomes of important cereal species can be manipulated by altering the composition of root exudates, and support ongoing attempts to improve plant production by manipulating the root microbiome.


Assuntos
Microbiota/fisiologia , Oryza/metabolismo , Exsudatos de Plantas/metabolismo , Raízes de Plantas/microbiologia , Rizosfera , Microbiologia do Solo , Triticum/metabolismo , Produtos Agrícolas/metabolismo , Produtos Agrícolas/microbiologia , Solo/química
6.
Biochem Biophys Res Commun ; 534: 485-490, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33239166

RESUMO

To identify drugs that could potentially be used to treat infection with SARS-CoV-2, a high throughput 384-well assay was developed to measure the binding of the receptor binding domain (RBD) of the viral S1 protein to its main receptor, angiotensin converting enzyme 2 (ACE2). The RBD was fused to both a HiBIT tag and an IL6 secretion signal to enable facile collection from the cell culture media. The addition of culture media containing this protein, termed HiBIT-RBD, to cells expressing ACE2 led to binding that was specific to ACE2 and both time and concentration dependant, Binding could be inhibited by both RBD expressed in E. coli and by a full length S1 - Fc fusion protein (Fc-fused S1) expressed in eukaryotic cells. The mutation of residues that are known to play a role in the interaction of RBD with ACE2 also reduced binding. This assay may be used to identify drugs which inhibit the viral uptake into cells mediated by binding to ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Luciferases/metabolismo , Receptores Virais/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/genética , Antivirais/metabolismo , Antivirais/uso terapêutico , Sítios de Ligação/genética , COVID-19/metabolismo , COVID-19/virologia , Humanos , Luciferases/genética , Nanotecnologia/métodos , Ligação Proteica , Domínios Proteicos , Receptores Virais/genética , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Tratamento Farmacológico da COVID-19
7.
New Phytol ; 229(3): 1268-1277, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32929739

RESUMO

Phosphate-solubilising microorganisms (PSM) are often reported to have positive effects on crop productivity through enhanced phosphorus (P) nutrition. Our aim was to evaluate the validity of this concept. Most studies that report 'positive effects' of PSM on plant growth have been conducted under controlled conditions, whereas field experiments more frequently fail to demonstrate a positive response. Many studies have indicated that the mechanisms seen in vitro do not translate into improved crop P nutrition in complex soil-plant systems. Furthermore, associated mechanisms are often not rigorously assessed. We suggest that PSM do not mobilise sufficient P to change the crops' nutritional environment under field conditions. The current concept, in which PSM solubilise P 'for the plant' should thus be revised. Although PSM have the capacity to solubilise P to meet their own needs, it is the turnover of the microbial biomass that subsequently provides P to plants over a longer time. Therefore, the existing concept of PSM function is unlikely to deliver a reliable strategy for increasing crop P nutrition. A further mechanistic understanding is needed to determine how P mobilisation by PSM as a component of the whole soil community can be manipulated to become more effective for plant P nutrition.


Assuntos
Fosfatos , Solo , Agricultura , Produtos Agrícolas , Fósforo , Microbiologia do Solo
8.
Exp Physiol ; 106(1): 233-243, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32462715

RESUMO

NEW FINDINGS: What is the central question of this study? Fire service instructors are frequently exposed to live fire scenarios, representing the most extreme chronic occupational heat exposure. These individuals report a series of unique health issues. We sought to identify whether the number of exposures completed was associated with inflammatory and immunological markers and symptoms of ill health. What is the main finding and its importance? Fire service instructors exhibit greater levels of inflammatory markers in comparison to firefighters. The number of exposures to fire is positively related to the prevalence of ill health and inflammation. Implementation of a proposed limit of nine exposures per month might be appropriate to minimize health issues. ABSTRACT: Fire Service Instructors (FSIs) experience ∼10 times more fire exposures than firefighters (FFs), and the increased physiological stress from this potentially puts them at risk of ill health and future cardiac events. The aim of the study was to establish whether FSIs exhibit elevated biomarkers associated with cardiac event risk, identify whether FSIs experience systemic inflammation linked to the frequency of fire exposure and evaluate a proposed exposure limit of nine exposures per month. Blood samples were collected from 110 Fire Service personnel (mean ± SD, age,44 ± 7 years; height, 178.1 ± 7.1 cm; and body mass, 84.3 ± 12.0 kg; FSIs n = 53 and FFs n = 57) for biomarker analysis. Work history details were collected from all participants. Participants with biomarker concentrations above healthy reference ranges were classified as being 'at risk'. The neutrophil-to-lymphocyte ratio, platelet count, cardiac troponin T, interleukin (IL)-6, IL-1ß, C-reactive protein and immunoglobulin G were greater in FSIs than in FFs (P < 0.05). Multiple regression analysis revealed that 18.8% of IL-6, 24.9% of IL-1ß, 29.2% of C-reactive protein and 10.9% of immunoglobulin G variance could be explained by the number of exposures to heat per month. Odds ratios revealed that those FSIs above the nine per month exposure limit were six to 12 times more likely to be classified as 'at risk' and were 16 times more likely to experience symptoms of ill health. Increased cytokine levels suggest that FSIs experience systemic inflammation, which is related to symptoms of ill health. We propose that an exposure limit could reduce the prevalence of these biomarker risk factors and ill health.


Assuntos
Temperatura Alta/efeitos adversos , Inflamação/sangue , Exposição Ocupacional , Estresse Fisiológico/fisiologia , Adulto , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Bombeiros , Humanos , Masculino , Pessoa de Meia-Idade
9.
Physiol Plant ; 173(3): 1030-1047, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34263457

RESUMO

Differences in root morphology and acclimation to low-phosphorus (P) soil were examined among eight legume species from the Trifolium Section Tricocephalum to understand how these root attributes determine P acquisition. Ornithopus sativus was included as a highly P-efficient benchmark species. Plants were grown as microswards in pots with five rates of P supplied in a topsoil layer to mimic uneven P distribution within a field soil profile. Topsoil and subsoil roots were harvested separately to enable measurement of the nutrient-foraging responses. Critical P requirement (lowest P supply for maximum yield) varied over a threefold range, reflecting differences in root morphology and acclimation of nutrient-foraging roots to P stress. Among the species, there was a 3.2-fold range in root length density, a 1.7-fold range in specific root length, and a 2.1-fold range in root hair length. O. sativus had the lowest critical P requirement, displayed a high root length density, the highest specific root length, and the longest root hairs. Acquisition of P from P-deficient soil was facilitated by development of a large root hair cylinder (i.e. a large root-soil interface). This, in turn, was determined by the intrinsic root morphology attributes of each genotype, and the plasticity of its root morphology response to internal P stress. Root acclimation in low-P soil by all species was mostly associated with preferential allocation of mass to nutrient-foraging roots. Only O. sativus and four of the Trifolium species adjusted specific root length beneficially, and only O. sativus increased its root hair length in low-P soil.


Assuntos
Fósforo , Trifolium , Aclimatação , Raízes de Plantas , Solo
10.
Scand J Med Sci Sports ; 29(5): 663-668, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30664255

RESUMO

Endurance exercise is an established cause of cardiac troponin (cTn) elevation, of further interest is whether this rise represents clinical significance. This study compared cTnT rise in three cohorts of marathon runners using a high-sensitivity assay; control runners, those with known heart disease and runners who collapsed at the finish line. Control runners (n = 126) and runners with heart disease (n = 12) were prospectively recruited with cTnT levels measured pre-race and at race completion. Collapsed runners (n = 15) were retrospectively recruited. A mixed model ANCOVA was used to compare the three groups. Pre-race median cTnT for the control group and heart disease groups was 3.9 ng/L (IQR 3.1 ng/L) and 4.1 ng/L (IQR 3.4 ng/L). Post-race values for the three groups were control 45.6 ng/L (IQR 42.5 ng/L), heart disease 41.2 ng/L (IQR 36.1 ng/L), and collapsed 41.9 ng/L (IQR 57.8 ng/L). Post-race cTnT and cTnT change were significantly correlated with pre-race cTnT within the control group (r = 0.38 and 0.30, P < 0.01). There was no difference in post-race cTnT (adjusted for pre-race cTnT) between the three groups. None of the runners reported symptoms suggestive of acute myocardial infarction on follow-up. These results demonstrate that marathon running is associated with an asymptomatic cTnT rise for all runners, and this rise is significantly correlated to baseline cTnT levels, in addition, marathon runners with pre-existing cardiac pathology or who collapse at the finish line do not exhibit an increased cTnT rise compared to healthy runners.


Assuntos
Cardiopatias/sangue , Corrida/fisiologia , Troponina T/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Sports Sci ; 37(2): 163-172, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29932816

RESUMO

This study sought to establish perceptions of elite endurance athletes on the role and worth of altitude training. Elite British endurance runners were surveyed to identify the altitude and hypoxic training methods utilised, along with reasons for use, and any situational, cultural and behaviour factors influencing these. Prior to the 2012 Olympics Games, 39 athletes and 20 support staff (coaches/practitioners) completed an internet-based survey to establish differences between current practices and the accepted "best-practice". Almost all of the athletes (98%) and support staff (95%) surveyed had utilised altitude and hypoxic training, or had advised it to athletes. 75% of athletes believed altitude and hypoxia to be a "very important" factor in their training regime, with 50% of support staff believing the same. Athletes and support staff were in agreement of the methods of altitude training utilised (i.e. 'hypoxic dose' and strategy), with camps lasting 3-4 weeks at 1,500-2,500 m being the most popular. Athletes and support staff are utilising altitude and hypoxic training methods in a manner agreeing with research-based suggestions. The survey identified a number of specific challenges and priorities, which could provide scope to optimise future altitude training methods for endurance performance in these elite groups.


Assuntos
Altitude , Atletas/psicologia , Percepção/fisiologia , Condicionamento Físico Humano/métodos , Resistência Física/fisiologia , Corrida/fisiologia , Comportamento Competitivo/fisiologia , Estudos Transversais , Humanos , Hipóxia , Tutoria , Inquéritos e Questionários , Reino Unido
12.
J Therm Biol ; 82: 1-9, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31128636

RESUMO

OBJECTIVES: Fire Service Instructors (FSI) experience repeated fire exposures a median of 13 ±â€¯8 times a month; consequently they may develop an acclimatised state. However, the chronic immunological implications of heat acclimation are yet to be understood. This study aimed to establish whether FSI exhibit an increased heat tolerance and altered immunological response to heat exposures, compared to non-exposed individuals. The study also aimed to identify if heat tolerance is related to symptoms of ill health. METHODS: Twenty-two participants were recruited: 11 FSI (age: 41 ±â€¯7 yrs, body mass: 77.4 ±â€¯12.2 kg, height: 174.1 ±â€¯8.2 cm) and 11 non-exposed controls (CON) (age: 41 ±â€¯7 yrs, body mass: 75.9 ±â€¯12.2 kg, height: 177.0 ±â€¯8.1 cm). Participants completed a 40 min heat occupational tolerance test (HOTT) exercising at 6 W kg-1 (50.0 ±â€¯1.0 °C, 12.3 ±â€¯3.3% relative humidity) on two occasions, separated by 2 months. Physiological and perceptual measures were collected throughout and venous blood samples were collected prior to and post exposure. RESULTS: FSI displayed significantly reduced peak rectal temperature (Tre) (-0.42 °C), change in Tre (-0.33 °C), and thermal sensation (-1.0) and increased sweat rate (+0.25 L h-1) at the end of the HOTT compared to CON (p < 0.05). FSI exhibited similar responses to the HOTT as CON for all haematological variables. However, resting interleukin-6, interleukin-1ß, and immunoglobulin G were significantly greater in FSI than CON. There was no difference in responses following the 2 month working period. FSI peak Tre was negatively correlated with symptoms of ill health (rpb = -0.473, p = 0.026) and the number of fire exposures in the previous 2 weeks (rs = -0.589, p = 0.004). CONCLUSION: Despite increased heat tolerance compared to non-exposed individuals, FSI may develop a maladaptation to repeated fire exposures, with elevated resting cytokine levels and an increased prevalence of ill health symptoms.


Assuntos
Termotolerância , Adulto , Regulação da Temperatura Corporal , Teste de Esforço , Bombeiros , Resposta ao Choque Térmico , Temperatura Alta , Humanos , Imunoglobulina G/sangue , Inflamação/sangue , Inflamação/etiologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos
13.
J Occup Environ Hyg ; 16(1): 27-40, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30277854

RESUMO

Fire service instructors (FSI) regularly experience different types of fire exercises, however the strain experienced from these scenarios is not well understood. This study aims to identify the physiological and perceptual strain of Fire Service Instructors (FSI) to three training exercises: DEMO, ATTACK, COMPARTMENT, and the different roles performed: SETTER, INSTRUCTOR. The study also aims to assess the effect that different exercise patterns over a day (BOX, MULTI, COMBINATION) have on immunological responses. Sixteen FSI (age: 41 ± 8 years, body mass: 83.7 ± 6.7 kg, height: 177.0 ± 6.7 cm) were recruited, with 10 FSI completing the three exercises. Physiological and perceptual measures were collected prior to and immediately post each exercise. Venous blood samples were collected at the beginning and end of each day. One-way analysis of variance (ANOVA) were conducted to assess differences in physiological variables between exercise types, independent samples t-tests were conducted between roles. Day changes in hematological variables were assessed by paired sample t-tests and analyzed by one-way ANOVAs to identify differences between exercise patterns. The COMPARTMENT exercise resulted in a greater change in rectal temperature (ΔTre) (0.49 ± 0.28 °C) than both the DEMO (0.23 ± 0.19 °C, p = 0.045) and ATTACK (0.27 ± 0.22 °C, p = 0.016). Within the COMPARTMENT exercise, the SETTER resulted in a greater ΔTre and rating of perceived exertion than the INSTRUCTOR (0.67 ± 0.29 °C vs. 0.43 ± 0.18 °C, p = 0.027 and 14 ± 2 vs. 11 ± 2, p = 0.001, respectively). Following a day of fire exercises white blood cells (WBC), neutrophils, lymphocytes (LYMPH), monocytes (MONO), platelets (PLT), mean platelet volume (MPV), Interleukin (IL)-6, and cardiac troponin T (cTnT) all increased (p < 0.05). Exercise patterns containing a COMPARTMENT exercise resulted in greater PLT, MPV, and IL-6. Total daily variation in ΔTre was correlated with post-exercise WBC, MONO, and LYMPH. COMPARTMENT exercises produce the greatest physiological strain, with the SETTER role within this exercise causing the greatest ΔTre. Although predominately physiological responses remain within safe limits. Exercise patterns that include a COMPARTMENT exercise also generate a greater inflammatory response.


Assuntos
Bombeiros/educação , Incêndios , Exposição Ocupacional/efeitos adversos , Adulto , Contagem de Células Sanguíneas , Temperatura Corporal/fisiologia , Feminino , Temperatura Alta , Humanos , Inflamação/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estresse Ocupacional/fisiopatologia , Troponina T/sangue , Reino Unido
14.
Bioorg Med Chem Lett ; 28(9): 1652-1656, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29588214

RESUMO

Our previous studies demonstrated that cycleanine, a macrocyclic bisbenzylisoquinoline (BBIQ) alkaloid, showed potent anti-ovarian cancer activity via apoptosis induction. Here, we synthesized two novel (aminoalkyl)cycleanine analogues (2 and 3) through a simple and efficient two-step reaction starting from cycleanine isolated from Triclisia subcordata Oliv. These analogues showed greater potency than the unmodified cycleanine in three human ovarian cancer cell lines. Both 2 and 3 induced apoptosis in ovarian cancer cells by activations of caspases 3/7, cleavage of PARP, increase in subG1 cell cycle phase and in the percentage of apoptotic cells. Further confocal fluorescence microscopy analysis confirmed the cellular uptake of alkaloids in ovarian cancer cells by using the unique (alkynyl)cycleanine (3) via click chemistry reaction. Our results suggest that cycleanine could be a hit compound for the future development in attacking ovarian cancer.


Assuntos
Alcaloides/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Isoquinolinas/farmacologia , Alcaloides/síntese química , Alcaloides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoquinolinas/síntese química , Isoquinolinas/química , Menispermaceae/química , Estrutura Molecular , Relação Estrutura-Atividade
15.
Bioorg Med Chem Lett ; 28(7): 1219-1222, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29519737

RESUMO

Thymoquinone (TQ), 2-isopropyl-5-methyl-1,4-benzoquinone, a natural product isolated from Nigella sativa L., has previously been demonstrated to exhibit antiproliferative activity in vitro against a range of cancers as well as the human malarial parasite Plasmodium falciparum. We describe here the synthesis of a series of analogues of TQ that explore the potential for nitrogen-substitution to this scaffold, or reduction to a hydroquinone scaffold, in increasing the potency of this antiproliferative activity against ovarian cancer cell lines and P. falciparum. In addition, alkyl or halogen-substituted analogues were commercially sourced and tested in parallel. Several TQ analogues with improved potency against ovarian cancer cells and P. falciparum were found, although this increase is suggested to be moderate. Key aspects of the structure activity relationship that could be further explored are highlighted.


Assuntos
Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Benzoquinonas/farmacologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/síntese química , Antimaláricos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Benzoquinonas/síntese química , Benzoquinonas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
16.
Physiol Plant ; 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29498417

RESUMO

Citrate and phytase root exudates contribute to improved phosphorus (P) acquisition efficiency in Nicotiana tabacum (tobacco) when both exudates are produced in a P deficient soil. To test the importance of root intermingling in the interaction of citrate and phytase exudates, Nicotiana tabacum plant-lines with constitutive expression of heterologous citrate (Cit) or fungal phytase (Phy) exudation traits were grown under two root treatments (roots separated or intermingled) and in two soils with contrasting soil P availability. Complementarity of plant mixtures varying in citrate efflux rate and mobility of the expressed phytase in soil was determined based on plant biomass and P accumulation. Soil P composition was evaluated using solution 31 P NMR spectroscopy. In the soil with limited available P, positive complementarity occurred in Cit+Phy mixtures with roots intermingled. Root separation eliminated positive interactions in mixtures expressing the less mobile phytase (Aspergillus niger PhyA) whereas positive complementarity persisted in mixtures that expressed the more mobile phytase (Peniophora lycii PhyA). Soils from Cit+Phy mixtures contained less inorganic P and more organic P compared to monocultures. Exudate-specific strategies for the acquisition of soil P were most effective in P-limited soil and depended on citrate efflux rate and the relative mobility of the expressed phytase in soil. Plant growth and soil P utilization in plant systems with complementary exudation strategies are expected to be greatest where exudates persist in soil and are expressed synchronously in space and time.

17.
J Therm Biol ; 78: 42-50, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30509666

RESUMO

Heat tolerance tests identify those susceptible to heat illnesses and monitor heat adaptations. Currently, tolerance tests do not replicate the uncompensable heat strain environments experienced in some occupations. In addition, tests can take up to 2 h to complete, and cannot offer intra and inter individual comparisons, due to the use of a fixed exercise intensity. This study aimed to assess the validity and reliability of a new heat occupational tolerance test (HOTT: 40 min at 6 W kg-1 metabolic heat production, 50 °C 10% RH, in protective clothing) to the standard heat tolerance test (HTT: 2 h walk at 5 km h-1 1% gradient, 40 °C 40% RH, in shorts and t-shirt). Eighteen participants (age: 21 ±â€¯3 yrs, body mass: 81.3 ±â€¯5.9 kg) completed trials to assess the validity and/or reliability of the HOTT. Peak rectal temperature (Tre) displayed strong agreement and low measurement error (0.19 °C) between HTT (38.7 ±â€¯0.4 °C) and HOTT (38.6 ±â€¯0.4 °C). Strong agreement was also displayed for physiological and perceptual measures between the two HOTT trials, including peak Tre (38.5 ±â€¯0.4 °C vs. 38.5 ±â€¯0.4 °C) and peak heart rate (182 ±â€¯20 b min-1 vs. 182 ±â€¯21 b min-1). The HOTT is the first tolerance test that assesses individuals' responses whilst wearing protective clothing in high temperatures. It can consistently identify individuals' levels of heat tolerance within a reduced time frame. In addition, it allows for participant monitoring over time and comparisons between individuals to be made. A continuum based approach is recommended when assessing individuals' responses to the HOTT.


Assuntos
Transtornos de Estresse por Calor/fisiopatologia , Monitorização Fisiológica/métodos , Doenças Profissionais/fisiopatologia , Termotolerância , Temperatura Corporal , Estudos de Viabilidade , Transtornos de Estresse por Calor/urina , Humanos , Masculino , Monitorização Fisiológica/normas , Doenças Profissionais/urina , Distribuição Aleatória , Respiração , Adulto Jovem
18.
J Strength Cond Res ; 32(5): 1366-1375, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28486332

RESUMO

James, CA, Richardson, AJ, Watt, PW, Willmott, AGB, Gibson, OR, and Maxwell, NS. Short-term heat acclimation and precooling, independently and combined, improve 5-km time trial performance in the heat. J Strength Cond Res 32(5): 1366-1375, 2018-Following heat acclimation (HA), endurance running performance remains impaired in hot vs. temperate conditions. Combining HA with precooling (PC) demonstrates no additive benefit in intermittent sprint, or continuous cycling exercise protocols, during which heat strain may be less severe compared to endurance running. This study investigated the effect of short-term HA (STHA) combined with mixed methods PC, on endurance running performance and directly compared PC and HA. Nine amateur trained runners completed 5-km treadmill time trials (TTs) in the heat (32° C, 60% relative humidity) under 4 conditions; no intervention (CON), PC, short-term HA (5 days-HA) and STHA with PC (HA + PC). Mean (±SD) performance times were; CON 1,476 (173) seconds, PC 1,421 (146) seconds, HA 1,378 (116) seconds and HA + PC 1,373 (121) seconds. This equated to the following improvements versus CON; PC -3.7%, HA -6.6% and HA + PC -7.0%. Statistical differences were only observed between HA and CON (p = 0.004, d = 0.68, 95% CI [-0.27 to 1.63]) however, similar effect sizes were observed for HA + PC vs. CON (d = 0.70, 95% CI [-0.25 to 1.65]), with smaller effects between PC vs. CON (d = 0.34, 95% CI [-0.59 to 1.27]), HA vs. PC (d = 0.33, 95% CI [-0.60 to 1.26]) and HA + PC vs. PC (d = 0.36, 95% CI [-0.57 to 1.29]). Pilot testing revealed a TT typical error of 16 seconds (1.2%). Precooling offered no further benefit to performance in the acclimated individual, despite modest alleviation of physiological strain. Maintenance of running speed in HA + PC, despite reduced physiological strain, may indicate an inappropriate pacing strategy therefore, further familiarization is recommended to optimize a combined strategy. Finally, these data indicate HA, achieved through cycle training, yields a larger ergogenic effect than PC on 5-km running performance in the heat, although PC remains beneficial when HA is not possible.


Assuntos
Aclimatação/fisiologia , Regulação da Temperatura Corporal/fisiologia , Temperatura Baixa , Temperatura Alta , Corrida/fisiologia , Adulto , Atletas , Desempenho Atlético/fisiologia , Teste de Esforço , Feminino , Humanos , Masculino
19.
J Sports Sci ; 35(22): 2249-2256, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27935427

RESUMO

Multistage, ultra-endurance events in hot, humid conditions necessitate thermal adaptation, often achieved through short term heat acclimation (STHA), to improve performance by reducing thermoregulatory strain and perceptions of heat stress. This study investigated the physiological, perceptual and immunological responses to STHA prior to the Marathon des Sables. Eight athletes (age 42 ± 4 years and body mass 81.9 ± 15.0 kg) completed 4 days of controlled hyperthermia STHA (60 min·day‒1, 45°C and 30% relative humidity). Pre, during and post sessions, physiological and perceptual measures were recorded. Immunological measures were recorded pre-post sessions 1 and 4. STHA improved thermal comfort (P = 0.02), sensation (P = 0.03) and perceived exertion (P = 0.04). A dissociated relationship between perceptual fatigue and Tre was evident after STHA, with reductions in perceived Physical (P = 0.04) and General (P = 0.04) fatigue. Exercising Tre and HR did not change (P > 0.05) however, sweat rate increased 14% (P = 0.02). No changes were found in white blood cell counts or content (P > 0.05). Four days of STHA facilitates effective perceptual adaptations, without compromising immune status prior to an ultra-endurance race in heat stress. A greater physiological strain is required to confer optimal physiological adaptations.


Assuntos
Aclimatação , Clima Desértico , Temperatura Alta , Corrida/fisiologia , Aclimatação/imunologia , Aclimatação/fisiologia , Adulto , Atletas , Humanos , Masculino , Sudorese
20.
J Therm Biol ; 63: 41-48, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28010814

RESUMO

Fire Service Instructors frequently experience high levels of physiological and perceptual strain during live fire exposures. Instructors are also at risk of cardiovascular illnesses, with cardiac death being the greatest cause of fire fighter death. Current practice for UK instructors is to select undergarment type based on personal preference, between a boiler suit (BOILER) and a wicking base layer (WBL). Research suggests that shorts and t-shirt (SHORTS) may also be a beneficial alternative undergarment choice. The UK South East Fire Service requested an investigation to identify if undergarment selection can lessen the strain experienced by instructors, and reduce the acute inflammatory response to fire exposures. Eight males completed three 45min sessions in a heat chamber (49.5±1.4°C and 16.9±4.3% RH) whilst performing intermittent walking. At the end of heat exposure change in heart rate was not effected by garment type (p=0.061, ηp2=0.373). Change in rectal temperature was different between garments (p=0.009, ηp2=0.271), with trends suggesting that BOILER resulted in a greater change (1.03±0.60°C) than SHORTS (0.76±0.37°C, p=0.589, d=0.21) and WBL (0.72±0.33°C, p=0.545, d=0.25). Interleukin-6 post exposure was greater for BOILER (6.96±0.28pgmL-1) than both SHORTS (6.59±0.30pgmL-1, p=0.043, d=0.42) and WBL (6.45±0.43pgmL-1, p=0.031, d=0.51). Overall, undergarment type had little impact on physiological or perceptual strain. However, wearing WBL or SHORTS may reduce the inflammatory response, and consequently decrease the risk of cardiovascular events.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Bombeiros , Temperatura Alta/efeitos adversos , Interleucina-6/sangue , Doenças Profissionais/prevenção & controle , Roupa de Proteção/normas , Estresse Psicológico/prevenção & controle , Temperatura Corporal , Doenças Cardiovasculares/etiologia , Humanos , Masculino , Doenças Profissionais/etiologia , Percepção , Roupa de Proteção/efeitos adversos , Estresse Psicológico/etiologia , Adulto Jovem
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