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1.
Ecol Appl ; 34(4): e2965, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38629596

RESUMO

Habitat loss is affecting many species, including the southern mountain caribou (Rangifer tarandus caribou) population in western North America. Over the last half century, this threatened caribou population's range and abundance have dramatically contracted. An integrated population model was used to analyze 51 years (1973-2023) of demographic data from 40 southern mountain caribou subpopulations to assess the effectiveness of population-based recovery actions at increasing population growth. Reducing potential limiting factors on threatened caribou populations offered a rare opportunity to identify the causes of decline and assess methods of recovery. Southern mountain caribou abundance declined by 51% between 1991 and 2023, and 37% of subpopulations were functionally extirpated. Wolf reduction was the only recovery action that consistently increased population growth when applied in isolation, and combinations of wolf reductions with maternal penning or supplemental feeding provided rapid growth but were applied to only four subpopulations. As of 2023, recovery actions have increased the abundance of southern mountain caribou by 52%, compared to a simulation with no interventions. When predation pressure was reduced, rapid population growth was observed, even under contemporary climate change and high levels of habitat loss. Unless predation is reduced, caribou subpopulations will continue to be extirpated well before habitat conservation and restoration can become effective.


Assuntos
Conservação dos Recursos Naturais , Espécies em Perigo de Extinção , Rena , Animais , Rena/fisiologia , Conservação dos Recursos Naturais/métodos , Modelos Biológicos , Dinâmica Populacional , Lobos/fisiologia , Ecossistema
2.
Phys Rev Lett ; 129(20): 201801, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36461983

RESUMO

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

3.
Ecol Appl ; 32(8): e2714, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36184581

RESUMO

A clear connection between basic research and applied management is often missing or difficult to discern. We present a case study of integration of basic research with applied management for estimating abundance of gray wolves (Canis lupus) in Montana, USA. Estimating wolf abundance is a key component of wolf management but is costly and time intensive as wolf populations continue to grow. We developed a multimodel approach using an occupancy model, mechanistic territory model, and empirical group size model to improve abundance estimates while reducing monitoring effort. Whereas field-based wolf counts generally rely on costly, difficult-to-collect monitoring data, especially for larger areas or population sizes, our approach efficiently uses readily available wolf observation data and introduces models focused on biological mechanisms underlying territorial and social behavior. In a three-part process, the occupancy model first estimates the extent of wolf distribution in Montana, based on environmental covariates and wolf observations. The spatially explicit mechanistic territory model predicts territory sizes using simple behavioral rules and data on prey resources, terrain ruggedness, and human density. Together, these models predict the number of packs. An empirical pack size model based on 14 years of data demonstrates that pack sizes are positively related to local densities of packs, and negatively related to terrain ruggedness, local mortalities, and intensity of harvest management. Total abundance estimates for given areas are derived by combining estimated numbers of packs and pack sizes. We estimated the Montana wolf population to be smallest in the first year of our study, with 91 packs and 654 wolves in 2007, followed by a population peak in 2011 with 1252 wolves. The population declined ~6% thereafter, coincident with implementation of legal harvest in Montana. Recent numbers have largely stabilized at an average of 191 packs and 1141 wolves from 2016 to 2020. This new approach accounts for biologically based, spatially explicit predictions of behavior to provide more accurate estimates of carnivore abundance at finer spatial scales. By integrating basic and applied research, our approach can therefore better inform decision-making and meet management needs.


Assuntos
Lobos , Animais , Humanos , Ecossistema , Densidade Demográfica , Comportamento Social , Montana
4.
J Appl Microbiol ; 130(2): 464-477, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32687650

RESUMO

AIMS: To understand the genetics involved in surface attachment and biofilm formation of Listeria monocytogenes. METHODS AND RESULTS: An in vitro screen of a Himar1 transposon library of L. monocytogenes strain 15G01 identified three transposants that produced significantly different biofilm levels when compared to the wild-type strain; two mutants exhibited enhanced biofilm formation and one produced less biofilm biomass than the wild-type. The mutant 15G01 mprF::Himar1, which had a transposon insertion in the mprF gene, was selected for further analysis. The mutant produced a more densely populated biofilm on solid surfaces such as stainless steel and polystyrene, as determined using scanning electron and light microscopy. The 15G01 mprF::Himar1 mutant remained viable in biofilms, but showed an increase in sensitivity to the cationic antimicrobial gallidermin. The mutant also displayed reduced invasiveness in CaCo-2 intestinal cells, suggesting virulence properties are compromised by the inactivation of mprF. CONCLUSIONS: Biofilm formation and gallidermin resistance of L. monocytogenes is influenced by mprF, but this trait is associated with a compromise in invasiveness. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of pathogenic microorganisms in the food processing environment can cause a significant problem, especially when these microorganisms are established as biofilms. This study shows that the inactivation of the mprF gene results in enhanced biofilm formation and abiotic surface attachment of L. monocytogenes.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana/genética , Listeria monocytogenes/fisiologia , Proteínas de Bactérias/genética , Células CACO-2 , Humanos , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/genética , Listeria monocytogenes/patogenicidade , Mutação , Virulência/genética
5.
Proc Biol Sci ; 287(1941): 20201786, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33323093

RESUMO

Understanding whether organisms will be able to adapt to human-induced stressors currently endangering their existence is an urgent priority. Globally, multiple species moult from a dark summer to white winter coat to maintain camouflage against snowy landscapes. Decreasing snow cover duration owing to climate change is increasing mismatch in seasonal camouflage. To directly test for adaptive responses to recent changes in snow cover, we repeated historical (1950s) field studies of moult phenology in mountain hares (Lepus timidus) in Scotland. We found little evidence that population moult phenology has shifted to align seasonal coat colour with shorter snow seasons, or that phenotypic plasticity prevented increases in camouflage mismatch. The lack of responses resulted in 35 additional days of mismatch between 1950 and 2016. We emphasize the potential role of weak directional selection pressure and low genetic variability in shaping the scope for adaptive responses to anthropogenic stressors.


Assuntos
Adaptação Fisiológica , Lebres , Fenótipo , Pigmentos Biológicos , Animais , Mudança Climática , Cor , Humanos , Muda , Estações do Ano , Neve
6.
Nanotechnology ; 31(39): 395706, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32150734

RESUMO

After the recent finding that CrI3, displays ferromagnetic order down to its monolayer, extensive studies have followed to pursue new two-dimensional (2D) magnetic materials. In this article, we report on the growth of single crystal CrCl3 in the layered monoclinic phase. The system after mechanical exfoliation exhibits stability in ambient air (the degradation occurs on a time scale at least four orders of magnitude longer than is observed for CrI3). By means of mechanical cleavage and atomic force microscopy (AFM) combined with optical identification, we demonstrate the systematic isolation of single and few layer flakes onto 270 nm and 285 nm SiO2/Si (100) substrates with lateral size larger than graphene flakes isolated with the same method. The layer number identification has been carried with statistically significant data, quantifying the optical contrast as a function of the number of layers for up to six layers. Layer dependent optical contrast data have been fitted within the Fresnel equation formalism determining the real and imaginary part of the wavelength dependent refractive index of the material. A layer dependent (532 nm) micro-Raman study has been carried out down to two layers with no detectable spectral shifts as a function of the layer number and with respect to the bulk.

7.
Phys Rev Lett ; 121(22): 221801, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30547637

RESUMO

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

8.
Mol Cell Biochem ; 443(1-2): 111-119, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29075989

RESUMO

The aim of this study was to find the genetic, metabolic, and nutritional risk factors, which can be associated with uric acid (UA) level. The risk factors related to uricemia were assessed among 271 postmenopausal women without cardiometabolic disorders and hypolipidemic/hypoglycemic treatment selected from a cohort of 1423 obese postmenopausal women. The bioimpedance analysis and biochemical and genetic analyses were performed in two groups characterized by serum UA ≥ 4 mg/dL (238 µmol/L) and < 4 mg/dL. The TaqMan-based real-time PCR method was applied to assess the role of Pro12Ala of peroxisome proliferation-activated receptor (PPAR)gamma-2 and Trp64Arg of beta-3-adrenergic receptor (ADRB) polymorphisms. Women with UA level ≥ 4 mg/dL were characterized by larger body mass, triceps skinfold, waist circumference, body fat amount, and serum insulin, glucose, and triglyceride levels. There was no difference in dietary habits between the analyzed groups. Body mass, waist circumference, body fat amount, diastolic blood pressure, and serum insulin, glucose, high-density lipoprotein, and triglyceride levels, Homeostasis Model Assessment-Insulin Resistance, and energy from the dietary fat influence the UA level ≥ 4 mg/dL; however, the serum UA was not determined by Pro12Ala and Trp64Arg polymorphism analyses. The model of linear regression revealed that the group characterized by body mass index  ≥ 25 kg/m2 and glucose ≥ 100 mg/dL has 4 times increased risk of UA level (p = 0.0009); after adding triglycerides ≥ 150 mg/dL, the risk of UA increased 7 times (p = 0.0216). Increasing the level of UA ≥ 4 mg/dL is associated with overweight, hyperglycemia, and hypertriglyceridemia in women without a history of cardiometabolic disorders. A better management of metabolic factors could help prevent further increase in UA levels.


Assuntos
Obesidade , PPAR gama/genética , Fenótipo , Polimorfismo Genético , Pós-Menopausa , Receptores Adrenérgicos beta 1/genética , Ácido Úrico/sangue , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/genética , Pós-Menopausa/sangue , Pós-Menopausa/genética
9.
J Antimicrob Chemother ; 72(12): 3277-3282, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961773

RESUMO

OBJECTIVES: To investigate the molecular epidemiology, antimicrobial susceptibility and carbapenem resistance determinants of Acinetobacter baumannii isolates from respiratory tract samples of patients diagnosed with ventilator-associated pneumonia (VAP) who were enrolled in the MagicBullet clinical trial. METHODS: A. baumannii isolates were prospectively cultured from respiratory tract samples from 65 patients from 15 hospitals in Greece, Italy and Spain. Susceptibility testing was performed by broth microdilution. Carbapenem resistance determinants were identified by PCR and sequencing. Molecular epidemiology was investigated using rep-PCR (DiversiLab) and international clones (IC) were identified using our in-house database. RESULTS: Of 65 isolates, all but two isolates (97%) were resistant to imipenem and these were always associated with an acquired carbapenemase, OXA-23 (80%), OXA-40 (4.6%), OXA-58 (1.5%) or OXA-23/58 (1.5%). Resistance to colistin was 47.7%. Twenty-two isolates were XDR, and 20 isolates were pandrug-resistant (PDR). The majority of isolates clustered with IC2 (n = 54) with one major subtype comprising isolates from 12 hospitals in the three countries, which included 19 XDR and 16 PDR isolates. CONCLUSIONS: Carbapenem resistance rates were very high in A. baumannii recovered from patients with VAP. Almost half of the isolates were colistin resistant, and 42 (64.6%) isolates were XDR or PDR. Rep-PCR confirmed IC2 is the predominant clonal lineage in Europe and suggests the presence of an epidemic XDR/PDR A. baumannii clone that has spread in Greece, Italy and Spain. These data highlight the difficulty in empirical treatment of patients with A. baumannii VAP in centres with a high prevalence of carbapenem-resistant A. baumannii.


Assuntos
Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Genótipo , Grécia/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Tipagem Molecular , Reação em Cadeia da Polimerase , Estudos Prospectivos , Análise de Sequência de DNA , Espanha/epidemiologia
10.
Faraday Discuss ; 200: 579-598, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28574567

RESUMO

Organic compounds in the atmosphere vary widely in their molecular composition and chemical properties, so no single instrument can reasonably measure the entire range of ambient compounds. Over the past decade, a new generation of in situ, field-deployable mass spectrometers has dramatically improved our ability to detect, identify, and quantify these organic compounds, but no systematic approach has been developed to assess the extent to which currently available tools capture the entire space of chemical identity and properties that is expected in the atmosphere. Reduced-parameter frameworks that have been developed to describe atmospheric mixtures are exploited here to characterize the range of chemical properties accessed by a suite of instruments. Multiple chemical spaces (e.g. oxidation state of carbon vs. volatility, and oxygen number vs. carbon number) were populated with ions measured by several mass spectrometers, with gas- and particle-phase α-pinene oxidation products serving as the test mixture of organic compounds. Few gaps are observed in the coverage of the parameter spaces by the instruments employed in this work, though the full extent to which comprehensive measurement was achieved is difficult to assess due to uncertainty in the composition of the mixture. Overlaps between individual ions and regions in parameter space were identified, both between gas- and particle-phase measurements, and within each phase. These overlaps were conservatively found to account for little (<10%) of the measured mass. However, challenges in identifying overlaps and in accurately converting molecular formulas into chemical properties (such as volatility or reactivity) highlight a continued need to incorporate structural information into atmospheric measurements.

11.
Ecol Lett ; 19(3): 299-307, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26799459

RESUMO

Anthropogenic climate change has created myriad stressors that threaten to cause local extinctions if wild populations fail to adapt to novel conditions. We studied individual and population-level fitness costs of a climate change-induced stressor: camouflage mismatch in seasonally colour molting species confronting decreasing snow cover duration. Based on field measurements of radiocollared snowshoe hares, we found strong selection on coat colour molt phenology, such that animals mismatched with the colour of their background experienced weekly survival decreases up to 7%. In the absence of adaptive response, we show that these mortality costs would result in strong population-level declines by the end of the century. However, natural selection acting on wide individual variation in molt phenology might enable evolutionary adaptation to camouflage mismatch. We conclude that evolutionary rescue will be critical for hares and other colour molting species to keep up with climate change.


Assuntos
Mudança Climática , Cadeia Alimentar , Lebres/fisiologia , Longevidade , Seleção Genética , Animais , Muda , Fenótipo , Dinâmica Populacional , Crescimento Demográfico , Estações do Ano , Neve
12.
Clin Exp Immunol ; 183(1): 102-13, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26400440

RESUMO

Reliable risk assessment for biotherapeutics requires accurate evaluation of risk factors associated with immunogenicity. Immunogenicity risk assessment tools were developed and applied to investigate the immunogenicity of a fully human therapeutic monoclonal antibody, ATR-107 [anti-interleukin (IL)-21 receptor] that elicited anti-drug antibodies (ADA) in 76% of healthy subjects in a Phase 1 study. Because the ATR-107 target is expressed on dendritic cells (DCs), the immunogenicity risk related to engagement with DC and antigen presentation pathways was studied. Despite the presence of IL-21R on DCs, ATR-107 did not bind to the DCs more extensively than the control therapeutic antibody (PF-1) that had elicited low clinical ADA incidence. However, ATR-107, but not the control therapeutic antibody, was translocated to the DC late endosomes, co-localized with intracellular antigen-D related (HLA-DR) molecules and presented a dominant T cell epitope overlapping the complementarity determining region 2 (CDR2) of the light chain. ATR-107 induced increased DC activation exemplified by up-regulation of DC surface expression of CD86, CD274 (PD-L1) and CD40, increased expansion of activated DC populations expressing CD86(hi), CD40(hi), CD83(hi), programmed death ligand 1 (PD-L1)(hi), HLA-DR(hi) or CCR7(hi), as well as elevated secretion of tumour necrosis factor (TNF)-α by DCs. DCs exposed to ATR-107 stimulated an autologous T cell proliferative response in human donor cells, in concert with the detection of immunoglobulin (Ig)G-type anti-ATR-107 antibody response in clinical samples. Collectively, the enhanced engagement of antigen presentation machinery by ATR-107 was suggested. The approaches and findings described in this study may be relevant to identifying lower immunogenicity risk targets and therapeutic molecules.


Assuntos
Anticorpos Monoclonais/farmacologia , Células Dendríticas/efeitos dos fármacos , Linfócitos T/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Apresentação de Antígeno/efeitos dos fármacos , Antígenos CD/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Células Dendríticas/imunologia , Endossomos/metabolismo , Epitopos de Linfócito T/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Interleucinas/imunologia , Ativação Linfocitária/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
13.
Anim Genet ; 47(1): 68-80, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26592359

RESUMO

In this study, a whole transcriptome analysis of breast muscles was conducted in broiler chicken groups differing in shear force. Shear force is a determinant of tenderness, which in turn is one of the most important parameters of meat quality in chickens. In our analysis, a total of 11,560 transcripts and 9824 genes per sample were identified. In chickens with more tender meat, up-regulation of 19 genes and down-regulation of 49 genes was observed. The up-regulated gene group included the ASB2 gene, which is probably involved in the meat conversion process, as its product results in the degradation of filamins, proteins which form muscle fibres. In the down-regulated gene group, genes which play a role in lipogenesis (THRSP, PLIN1) and in collagen synthesis (P4HA3, LEPREL4, PCOLCE2, COL16A1, COL20A1, VWA1) were detected. Their presence suggests the involvement of the extracellular matrix in the determination of meat tenderness. Thus, our study identified a pool of genes that may participate in the tenderisation process in broiler chickens.


Assuntos
Galinhas/genética , Perfilação da Expressão Gênica , Carne , Animais , Colágeno/biossíntese , Matriz Extracelular/genética , Filaminas/genética , Regulação da Expressão Gênica , Lipogênese/genética , Dados de Sequência Molecular , Músculos/metabolismo
14.
Br Poult Sci ; 56(4): 452-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26042540

RESUMO

The aim of this study was to assess mRNA abundance of calpain 1 (CAPN1) and calpain 3 (CAPN3) in breast muscle of 80 fast-growing (FG) and slow-growing broilers (SG) and relate gene expression in relation to growth and Warner Bratzler (WB) shear force of breast muscle. The expression of CAPN1 and CAPN3 genes was higher in the FG compared to the SG line, but significant results were obtained only for CAPN1. The CAPN1 mRNA level was strongly dependent on line and gender interaction. Lower values of shear force were observed in the FG line, where a higher level of calpain expression was shown. A new panel of housekeeping genes (RPL4 and SDHA) for normalisation of gene expression in muscle tissues could be used in other studies of gene expression in chicken.


Assuntos
Proteínas Aviárias/genética , Calpaína/genética , Galinhas/genética , Expressão Gênica , Músculos Peitorais/fisiologia , Animais , Proteínas Aviárias/metabolismo , Calpaína/metabolismo , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Feminino , Masculino , Carne/análise , RNA Mensageiro/metabolismo
15.
Scand J Immunol ; 80(2): 75-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24845558

RESUMO

It is widely accepted that type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from an interaction between immunologic, genetic and environmental factors. However, the exact mechanism leading to the development of T1DM remains incomplete. There is a large body of evidence pointing towards the important role of toll-like receptor (TLR) activation and vitamin D deficiency in T1DM pathogenesis. In this article, we review the available data on the influence of TLRs' level of activation and vitamin D status on the risk of the development of T1DM in humans and rodent models. We also summarize the current information regarding the interactions between TLRs' level of activation, vitamin D status and various environmental factors, such as enteroviral infections, the gut microbiota and breastfeeding substitution, among others. Our results stipulate that vitamin D seems to protect against T1DM by reducing the TLRs' level of activation.


Assuntos
Diabetes Mellitus Tipo 1/genética , Receptores Toll-Like/imunologia , Deficiência de Vitamina D/metabolismo , Vitamina D/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/epidemiologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Camundongos , Ratos , Receptores de Calcitriol/imunologia , Receptores Toll-Like/biossíntese , Vitamina D/metabolismo
16.
Acta Virol ; 58(2): 185-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24957725

RESUMO

Chronic hepatitis B (CHB) is one of the most common infections worldwide. Currently approved treatments of CHB include nucleoside/nucleotide analogues (NAs). However, long-term NA therapy is associated with accumulation of resistant mutations within the hepatitis B virus (HBV) polymerase gene. The incidence of naturally occurring HBV mutations leading to primary antiviral resistance has not been fully elucidated yet. The objective of present study was to detect the frequency of mutations within the HBV polymerase gene in 263 patients naïve to nucleoside/nucleotide analogues. Prevalence of HBV Pol gene mutations secondary to NA treatment in patients without pre-existing antiviral resistance mutations was also examined. Retrospective analysis showed that HBV Pol gene mutations were present in 7 out of 263 patients prior to the treatment. Mutations observed in NA-naïve CHB patients were associated only with resistance to lamivudine and adefovir. Compensatory mutations were observed as well. In the course of antiviral treatment, HBV Pol gene mutations were identified in 65 out of the remaining 256 CHB patients (25.39%), while no mutations of any type were detected in 160 patients (62.5%). The profiles of detected mutations were comparable to those observed in other studies that focused on the analysis of clinically relevant NA-resistant mutations. In conclusion, we found out that antiviral resistance mutations may pre-exist in the overall viral population present in untreated patients, although the incidence of HBV Pol gene mutations in NA-naïve CHB patients was low and reached only up to 2.66%. However, possible circulation and transmission of NAs-resistant HBV mutants in human population should be taken into account.


Assuntos
Antivirais/uso terapêutico , Produtos do Gene pol/genética , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Mutação , Nucleosídeos/uso terapêutico , Nucleotídeos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Nucleosídeos/química , Nucleotídeos/química , Estudos Retrospectivos , Adulto Jovem
17.
Tissue Antigens ; 82(6): 387-96, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24498995

RESUMO

Four hundred and ninety-five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin-10 (IL-10) promoter genotype [rs18000896 (-1082 G/A), rs18000871 (-819 C/T) and rs18000872 (-592 C/A)] on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, grade > I) if transplanted from human leukocyte antigen (HLA) well-matched (10/10) unrelated donors (20/135 vs 39/117, P < 0.001, Pcorr = 0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (<10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P = 0.019, Pcorr = 0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor-recipient human leukocyte antigen (HLA) mismatch [odds ratio (OR) = 3.937, P = 0.001] and a lack of ACC haplotype in recipients (OR = 0.417, P = 0.013) played a significant role as independent risk factors of aGvHD grade > I. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL-10 haplotypes. It was seen at the time of hematological recovery (mean ± SEM: 3.80 ± 0.91% vs 2.06 ± 0.98%, P = 0.012) and 2 weeks later (5.32 ± 0.87% vs 2.50 ± 0.83%, P = 0.013); -592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P = 0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43 ± 0.22% vs 4.32 ± 0.71%, P = 0.051) measured 2 weeks after hematological recovery. Functional IL-10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.


Assuntos
Doença Enxerto-Hospedeiro/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Interleucina-10/genética , Regiões Promotoras Genéticas/genética , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Doença Aguda , Antígenos CD4/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Doença Enxerto-Hospedeiro/imunologia , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Polônia , Polimorfismo Genético , Risco , Irmãos
18.
Eur Rev Med Pharmacol Sci ; 17(22): 3056-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24302186

RESUMO

BACKGROUND: Phenylketonuria (PKU) is an inborn error of amino acid metabolism in which high phenylalanine (Phe) concentrations in the central nervous system adversely affect its development and functioning. In PKU high oxidative stress and inefficiency of free radical scavenging may lead to systemic chronic inflammation. We hypothesised that in PKU gut mucosa is chronically inflamed and that this leads to release of calprotectin from neutrophils and monocytes. AIM: The aim of this study was to compare intestinal mucosa inflammation status, as measured using fecal calprotectin, in patients with PKU irrespective of compliance, and healthy controls. PATIENTS AND METHODS: Forty-four patients with classical PKU were included in the study (21 male, 23 female; aged 0-41 years; mean ± SEM: 16.5 ± 1.7 years). Forty-eight healthy subjects (HS) aged 9-68 years (29.4 ± 2.6 years) comprised the control group, of whom 21 were male and 27 female. Among PKU patients 25 had normal Phe blood concentrations and in 19 they were elevated. In all subjects calprotectin stool concentrations were assessed (PhiCal ELISA, Calpro, Lysaker, Norway). RESULTS: Normal FC (fecal calprotectin) concentrations were found in 43 (97.7%) PKU patients and 46 (95.8%) HS. No correlation between dietary control of Phe blood concentrations and FC levels in PKU patients was found. CONCLUSIONS: No detectable intestinal inflammation occurs in phenylketonuria. Lack of dietary control and elevated Phe levels do not seem to be risk factors for inflammation of the mucosa of the gut.


Assuntos
Enterite/etiologia , Mucosa Intestinal/patologia , Fenilcetonúrias/complicações , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Fezes/química , Feminino , Humanos , Lactente , Recém-Nascido , Complexo Antígeno L1 Leucocitário/análise , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Tissue Antigens ; 79(3): 198-203, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22211793

RESUMO

Polymorphic variants of the IL2RA gene, which encodes high-affinity alpha subunit (CD25) of the interleukin-2 receptor, were recently found to affect the risk of several autoimmune disorders. This study was aimed to investigate the association of selected IL2RA polymorphisms (rs11594656, rs3118470, rs2104286 and rs7093069) with type 1 diabetes (T1D) in a Polish cohort comprising 445 patients and 671 healthy control subjects. The minor A allele at rs11594656 was found significantly less frequently among T1D subjects, compared with the control group [P = 0.011; odds ratio (OR) = 0.77; 95% confidence interval (CI) = 0.629-0.942]. In contrast, the minor C allele at rs3118470 appeared to be significantly associated with the occurrence of T1D (P = 0.003; OR = 1.30; 95% CI = 1.094-1.550). Two other IL2RA single nucleotide polymorphisms (SNPs) did not show significant differences among investigated groups. In conclusion, the study confirms the association of the IL2RA locus with T1D in the Polish population.


Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Variação Genética , Subunidade alfa de Receptor de Interleucina-2/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Polônia , Reação em Cadeia da Polimerase
20.
Scand J Immunol ; 76(1): 1-10, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22486930

RESUMO

Modified C-reactive protein (mCRP) has been reported to non-specifically bind to immunoglobulins; notwithstanding, the nature of these interactions is not clear. The aim of this study was to investigate the binding of antibodies directed against HSA and IgG to mCRP, fibrinogen (Fg), IgG, fibronectin (Fn) and C1q and its contaminants. We also studied the binding of mCRP to the antibodies directed towards receptors involved in CRP signalling (anti-CD32, anti-CD16). For the analysis of such interactions, a combination of ELISA and Western immunoblotting has been applied. The tested antibodies powerfully bound to either the contaminations of purified proteins (Fg, IgG, Fn and mCRP) or interacted directly with some of these proteins (C1q, mCRP, Fg). The effectiveness of anti-HSA binding to immobilized proteins was influenced by the antigenic specificity of the antibody, the content of various protein fractions in the contaminants of a given protein (albumin augmented the interactions), overall protein purity and a natural avidity of a given protein towards immunoglobulins. The relative binding of anti-HSA or anti-IgG to immobilized mCRP was considerably lower than that observed for plasma proteins. Furthermore, the strength of the direct interaction between immunoglobulins and mCRP varied from the lack of response (anti-HSA) or a negligible response (anti-IgG) to the relatively high signal (human IgG, anti-CD16, anti-CD32), as compared to the control. Based on these observations, we conclude that the binding of mCRP to immunoglobulins cannot be easily generalized as a kind of some universal phenomenon.


Assuntos
Proteína C-Reativa/imunologia , Imunoglobulina G/imunologia , Albumina Sérica/imunologia , Adulto , Western Blotting , Complemento C1q/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrinogênio/imunologia , Fibronectinas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade
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