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1.
Obes Surg ; 34(8): 3071-3083, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38951388

RESUMO

In recent years, there has been a gradual increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM), with bariatric surgery remaining the most effective treatment strategy for these conditions. Vertical sleeve gastrectomy (VSG) has emerged as the most popular surgical procedure for bariatric/metabolic surgeries, effectively promoting weight loss and improving or curing T2DM. The alterations in the gastrointestinal tract following VSG may improve insulin secretion and resistance by increasing incretin secretion (especially GLP-1), modifying the gut microbiota composition, and through mechanisms dependent on weight loss. This review focuses on the potential mechanisms through which the enhanced action of incretin and metabolic changes in the digestive system after VSG may contribute to the remission of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Gastrectomia , Obesidade Mórbida , Redução de Peso , Humanos , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Obesidade Mórbida/cirurgia , Indução de Remissão , Incretinas , Microbioma Gastrointestinal , Cirurgia Bariátrica/métodos , Resultado do Tratamento , Resistência à Insulina , Peptídeo 1 Semelhante ao Glucagon/metabolismo
2.
Acta Parasitol ; 69(1): 465-470, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38190015

RESUMO

PURPOSE: This study was carried out to assess the prevalence of Trypanosoma evansi infection in naturally diseased Dromedary camels in Dammam, Eastern region of Saudi Arabia. The detection of Trypanosoma evansi was performed using the parasitological, serological, and molecular diagnosis and a comparison between such methods were analyzed. In addition, evaluation of therapeutic efficacy of selected antitrypanosomal drugs, cymelarsan and quinapyrmine (aquin-1.5), was trialed for treatment of diagnosed infected cases. METHODS: A total 350 randomly selected camels were evaluated using thin blood smear (TBS), RoTat1.2 PCR and CATT/T. evansi techniques. RESULTS: The total prevalence was 6.9%, 7.7%, and 32.8% by TBS, RoTat1.2 PCR and CATT/T. evansi techniques, respectively. Although PCR detect T. evansi in more samples than TBS, the agreement was good (K = 0.9). Among the CATT/T. evansi results, PCR detect T. evansi in 12 and 15 CATT positive and negative camels, respectively, with low agreement (Kappa = 0.1). The use of cymelarsan and quinapyramine sulfate in the treatment of naturally infected cases demonstrated a very efficient therapeutic response. CONCLUSION: It was found that 1. Comparing the CATT/T. evansi and PCR results, the positivity of CATT was higher than PCR detection, while the agreement was poor (K = 0.1). 2. Cymelarsan and aquin-1.5 proved to be effective in the treatment of naturally infected camels, but cymelarsan presented with higher effectiveness (100%) than aquin-treated camels (83.3%). a 3. The use of cymelarsan and CATT is recommended for disease treatment and control.


Assuntos
Camelus , Compostos de Quinolínio , Triazinas , Tripanossomicidas , Trypanosoma , Tripanossomíase , Animais , Camelus/parasitologia , Trypanosoma/efeitos dos fármacos , Trypanosoma/genética , Tripanossomíase/veterinária , Tripanossomíase/epidemiologia , Tripanossomíase/tratamento farmacológico , Tripanossomíase/parasitologia , Arábia Saudita/epidemiologia , Tripanossomicidas/uso terapêutico , Tripanossomicidas/farmacologia , Prevalência , Reação em Cadeia da Polimerase/veterinária , Arsenicais/uso terapêutico , Masculino
3.
Biomolecules ; 14(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38254667

RESUMO

Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries and block nucleolytic degradation of the natural chromosome ends, although the detailed underlying mechanisms are not identical. In addition, the specialized telomere structure exerts a repressive epigenetic effect on expression of genes located at subtelomeres in a number of eukaryotic organisms. This so-called telomeric silencing also affects virulence of a number of microbial pathogens that undergo antigenic variation/phenotypic switching. Telomere proteins, particularly the RAP1 homologs, have been shown to be a key player for telomeric silencing. RAP1 homologs also suppress the expression of Telomere Repeat-containing RNA (TERRA), which is linked to their roles in telomere stability maintenance. The functions of RAP1s in suppressing telomere recombination are largely conserved from kinetoplastids to mammals. However, the underlying mechanisms of RAP1-mediated telomeric silencing have many species-specific features. In this review, I will focus on Trypanosoma brucei RAP1's functions in suppressing telomeric/subtelomeric DNA recombination and in the regulation of monoallelic expression of subtelomere-located major surface antigen genes. Common and unique mechanisms will be compared among RAP1 homologs, and their implications will be discussed.


Assuntos
RNA Longo não Codificante , Telômero , Animais , Telômero/genética , Epigenômica , Eucariotos , Mamíferos
4.
Front Cardiovasc Med ; 10: 1239153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107265

RESUMO

Background: Open abdominal aortic surgery carries many potential complications, with cardiac adverse events being the most significant concern. The Vascular Study Group Cardiac Risk Index (VSG-CRI) is a commonly used tool for predicting severe cardiac complications and guiding clinical decision-making. However, despite the potential prognostic significance of left ventricular wall motion abnormalities (LVWMAs) and reduced LV ejection fraction (LVEF) for adverse outcomes, the VSG-CRI model has not accounted for them. Hence, the main objective of this study was to analyze the added value of LV wall motion on the discriminatory power of the modified VSG-CRI in predicting major postoperative cardiac complications. Methods: A prospective study was conducted involving 271 patients who underwent elective abdominal aortic surgery between 2019 and 2021. VSG-CRI scores were calculated, and preoperative transthoracic echocardiography was conducted for all patients. Subsequently, a modified version of the VSG-CRI, accounting for reduced LVEF and LVWMAs, was developed and incorporated into the dataset. The postoperative incidence of the composite endpoint of major adverse cardiac events (MACEs), including myocardial infarction, clinically relevant arrhythmias treated with medicaments or by cardioversion, or congestive heart failure, was assessed at discharge from the index hospitalization, with adjudicators blinded to events. The predictive accuracy of both the original and modified VSG-CRI was assessed using C-Statistics. Results: In total, 61 patients (22.5%) experienced MACEs. Among these patients, a significantly higher proportion had preoperative LVWMAs compared to those without (62.3% vs. 32.9%, p < 0.001). Multivariable regression analysis revealed the VSG-CRI [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.21-1.77; p < 0.001] and LVWMA (OR 2.76; 95% CI 1.46-5.23; p = 0.002) as independent predictors of MACEs. Additionally, the modified VSG-CRI model demonstrated superior predictability compared to the baseline VSG-CRI model, suggesting an improved predictive performance for anticipating MACEs following abdominal aortic surgery [area under the curve (AUC) 0.74; 95% CI 0.68-0.81 vs. AUC 0.70; 95% CI 0.63-0.77; respectively]. Conclusion: The findings of this study suggest that incorporating preoperative echocardiography can enhance the predictive accuracy of the VSG-CRI for predicting MACEs after open abdominal aortic surgery. Before its implementation in clinical settings, external validation is necessary to confirm the generalizability of this newly developed predictive model across different populations.

5.
Bio Protoc ; 13(24): e4904, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38156032

RESUMO

Many organisms alternate the expression of genes from large gene sets or gene families to adapt to environmental cues or immune pressure. The single-celled protozoan pathogen Trypanosoma brucei spp. periodically changes its homogeneous surface coat of variant surface glycoproteins (VSGs) to evade host antibodies during infection. This pathogen expresses one out of ~2,500 VSG genes at a time from telomeric expression sites (ESs) and periodically changes their expression by transcriptional switching or recombination. Attempts to track VSG switching have previously relied on genetic modifications of ES sequences with drug-selectable markers or genes encoding fluorescent proteins. However, genetic modifications of the ESs can interfere with the binding of proteins that control VSG transcription and/or recombination, thus affecting VSG expression and switching. Other approaches include Illumina sequencing of the VSG repertoire, which shows VSGs expressed in the population rather than cell switching; the Illumina short reads often limit the distinction of the large set of VSG genes. Here, we describe a methodology to study antigenic switching without modifications of the ES sequences. Our protocol enables the detection of VSG switching at nucleotide resolution using multiplexed clonal cell barcoding to track cells and nanopore sequencing to identify cell-specific VSG expression. We also developed a computational pipeline that takes DNA sequences and outputs VSGs expressed by cell clones. This protocol can be adapted to study clonal cell expression of large gene families in prokaryotes or eukaryotes. Key features • This protocol enables the analysis of variant surface glycoproteins (VSG) switching in T. brucei without modifying the expression site sequences. • It uses a streamlined computational pipeline that takes fastq DNA sequences and outputs expressed VSG genes by each parasite clone. • The protocol leverages the long reads sequencing capacity of the Oxford nanopore sequencing technology, which enables accurate identification of the expressed VSGs. • The protocol requires approximately eight to nine days to complete.

6.
Sensors (Basel) ; 23(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37571640

RESUMO

The proportion of distributed generation systems in power grids is increasing, leading to the gradual emergence of weak grid characteristics. Moreover, using voltage-sourced grid-connected inverters can enhance the stability of a weak grid. However, due to the presence of background harmonics in weak grids, the grid voltage can cause significant distortions in the grid-connected current, which adversely affects the quality of the grid-connected current. This paper begins by briefly introducing the principle of the virtual synchronous generator (VSG). Then, the output current of the voltage source inverter is analyzed to elucidate the mechanism of harmonic current generation. Considering the distortion in the grid-connected current of the voltage source grid-connected inverter caused by background harmonics in the grid voltage, a harmonic current suppression strategy based on an adaptive virtual harmonic resistor is proposed. The proposed strategy employs a signal separation module based on multiple second-order generalized integrators connected through a cross-feedback network. This module effectively separates the fundamental and harmonic currents from the grid-connected current, extracts the amplitudes of the fundamental and harmonic currents through coordinate transformation, and adaptively adjusts the virtual harmonic resistance magnitude through the negative feedback control of the harmonic content (the ratio of the harmonic current amplitude to the fundamental current amplitude). These measures are used to enhance the quality of the grid-connected current. Additionally, the stability of the system is analyzed using the root locus of the open-loop transfer function. Finally, the effectiveness of the proposed method is validated through a combination of MATLAB/Simulink simulations and experimental results.

7.
Trop Anim Health Prod ; 55(4): 279, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37505344

RESUMO

Trypanosoma brucei evansi (T. b. evansi) is an enzootic organism found in Egyptian camels, which genetically classified into types A and B. To detect the parasite genotype circulating in Egyptian camels, we collected 94 blood samples from three distant districts and subjected them to different PCR assays; T. brucei repeat (TBR), internal transcribed spacer-1 (ITS-1), and variable surface glycoproteins (VSG) (RoTat 1. 2, JN 2118Hu) and EVAB PCRs. The highest prevalence was obtained with TBR (80/91; 87.9%), followed by ITS-1 (52/91; 57.1%), VSG JN 2118Hu (42/91; 46.2%), and VSG RoTat 1. 2 (34/91; 37.4%). We reported a different non-RoTat 1. 2 T. b. evansi for the first time in Egyptian camels. Results showed that 47 (58.7%) out of 80 samples were classified as T. b. evansi. Of these, 14 (29.8%) were RoTat 1. 2 type, 13 (27.6%) were non-RoTat 1. 2 type, and 20 (42.6%) samples were from mixed infection with both types. All samples were tested negative with EVAB PCR. RoTat 1. 2 T. b. evansi was the most prevalent in Giza and El Nubariyah, whereas, in Aswan, the only type detected was non-RoTat 1. 2 T. b. evansi. The nucleotide sequences of the VSG RoTat 1.2 and JN 2118Hu PCR products were submitted to DNA Data Bank of Japan (DDBJ) and GenBank under the accession numbers LC738852, and (OP800400-OP800403). Further research is required to increase the sample size and verify the new sequences to corroborate the prevalence of a new variant of non-RoTat 1.2 T. b. evansi in Egypt.


Assuntos
Trypanosoma brucei brucei , Trypanosoma , Tripanossomíase , Animais , Tripanossomíase/epidemiologia , Tripanossomíase/veterinária , Camelus/parasitologia , Egito/epidemiologia , Genótipo , Trypanosoma/genética
8.
Mol Biol Rep ; 50(9): 7347-7356, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37439897

RESUMO

BACKGROUND: Trypanosoma evansi is a protozoan parasite that can infect a wide range of animals and is widespread around the world. In this study, we analyzed four fatal cases of T. evansi infection using clinical, parasitological, and molecular approaches. We also explored the genetic diversity, demographic history, and population-genetic structure of T. evansi using available Rode Trypanozoon antigenic type (RoTat) 1.2 gene sequences. METHODS AND RESULTS: Clinical findings of infected animals revealed high fever, anemia, weakness, and anorexia. The animals were treated with diminazene aceturate, which was moderately effective, and hematobiochemical parameters showed changes in hemoglobin and glucose levels. The molecular and genetic diversity of T. evansi was analyzed using the RoTat 1.2 VSG gene. Phylogenetic and haplotype analysis revealed two distinct clusters of T. evansi circulating in India. The genetic diversity indices, neutrality tests, gene flow, and genetic differentiation outcomes confirmed the genetic diversity of the T. evansi population, with a lack of uniformity. The identification of two distinct clusters, exhibiting differential demographic histories and evolutionary forces, implies that the clusters may have undergone independent evolutionary trajectories or experienced different environmental pressures. CONCLUSION: The present findings underlined the need of an early and precise diagnosis in order to treat and control T. evansi infections, and the RoTat 1.2 VSG gene is an important genetic marker for understanding the genetic diversity and evolutionary history of T. evansi. This knowledge can be used to create tailored strategies to control and manage the infection in an endemic region.


Assuntos
Trypanosoma , Tripanossomíase , Animais , Cavalos , Cães , Tripanossomíase/veterinária , Tripanossomíase/epidemiologia , Tripanossomíase/parasitologia , Antígenos de Protozoários/genética , Filogenia , Trypanosoma/genética , Camelus/parasitologia , Variação Genética/genética
9.
Nutrients ; 15(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37375579

RESUMO

The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [11C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum (p = 0.032), posterior putamen (p = 0.012), and anterior caudate (p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Estriado Ventral , Feminino , Humanos , Dopamina/metabolismo , Projetos Piloto , Obesidade Mórbida/cirurgia , Obesidade Mórbida/metabolismo , Receptores de Dopamina D2 , Obesidade/cirurgia , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons , Estriado Ventral/diagnóstico por imagem , Estriado Ventral/metabolismo
10.
Sensors (Basel) ; 23(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37299809

RESUMO

The intelligent fault diagnosis of main circulation pumps is crucial for ensuring their safe and stable operation. However, limited research has been conducted on this topic, and applying existing fault diagnosis methods designed for other equipment may not yield optimal results when directly used for main circulation pump fault diagnosis. To address this issue, we propose a novel ensemble fault diagnosis model for the main circulation pumps of converter valves in voltage source converter-based high voltage direct current transmission (VSG-HVDC) systems. The proposed model employs a set of base learners already able to achieve satisfying fault diagnosis performance and a weighting model based on deep reinforcement learning that synthesizes the outputs of these base learners and assigns different weights to obtain the final fault diagnosis results. The experimental results demonstrate that the proposed model outperforms alternative approaches, achieving an accuracy of 95.00% and an F1 score of 90.48%. Compared to the widely used long and short-term memory artificial neural network (LSTM), the proposed model exhibits improvements of 4.06% in accuracy and 7.85% in F1 score. Furthermore, it surpasses the latest existing ensemble model based on the improved sparrow algorithm, with enhancements of 1.56% in accuracy and 2.91% in F1 score. This work presents a data-driven tool with high accuracy for the fault diagnosis of main circulation pumps, which plays a critical role in maintaining the operational stability of VSG-HVDC systems and satisfying the unmanned requirements of offshore flexible platform cooling systems.


Assuntos
Algoritmos , Eletricidade , Inteligência , Memória de Curto Prazo , Redes Neurais de Computação
11.
Microb Pathog ; 175: 105967, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603695

RESUMO

Surra is a major infectious disease of camels being caused by Trypanosoma evansi (T. evansi) in developing countries, including Egypt. However, the identification of changes in the T. evansi prevalence in Egypt is important. In this study, the prevalence of T. evansi and its associated risk factors as well as the genetic characterization of the parasite were estimated. Blood samples were collected from 163 camels from two governorates in Lower Egypt. PCR targeting RoTat 1.2VSG was used for the detection of T. evansi and internal transcribed spacer 1 (ITS-1) was used for sequencing analysis and genetic characterization. Overall prevalence was 19.6% using RoTat 1.2VSG. The risk of the infection in females was 4 times higher than in males (P = 0.0004, OR = 4; 95% CI = 0.79-8.96) and in camels with a history of clinical signs it was 2.3 times higher than camels without clinical signs (P = 0.04, OR = 2.3, 95% CI = 1.035-5.15). Analysis of the ITS-1 sequences of four T. evansi isolates showed little heterogeneity compared to similar sequences in the database. Sequence and phylogenetic analysis, based on the ITS-1 region, confirmed the presence of two distinct genotypes of T. evansi in Egyptian camels with more than 99% similarity with T. evansi isolates from different countries across the ITS-1 region and were closely related to Filipino and Chinese isolates. The results of the study can be used for the observation and prevention of disease and updating the epidemiological data.


Assuntos
Trypanosoma , Tripanossomíase , Animais , Feminino , Masculino , Camelus/parasitologia , Prevalência , Filogenia , Tripanossomíase/epidemiologia , Tripanossomíase/veterinária , Tripanossomíase/diagnóstico , Fatores de Risco
12.
Surg Endosc ; 37(4): 3090-3102, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927350

RESUMO

BACKGROUND: Vertical sleeve gastrectomy (VSG) has demonstrated to be safe; however, controversy remains on how to decrease major complications, particularly bleeding and leaks. There are variations in staple-line reinforcement techniques, including no reinforcement, oversewing, and buttressing. We sought to evaluate the effect of those methods on post-operative complications using the Metabolic and Bariatric Surgery Accreditation Quality Initiative Program (MBSAQIP) database. METHODS: The MBSAQIP was queried for patients who underwent VSG during 2015-2019. A propensity-matched analysis was performed between different staple-line reinforcement (SLR) methods, specifically No reinforcement (NR), Oversewing (OS), and Buttressing (BR). The primary outcome of interest was complications within 30 days. RESULTS: A total of 513,354 VSG cases were analyzed. The cohort was majority female (79.0%), with mean (SD) age of 44.2 ± 11.9 years and mean BMI of 45 ± 7.8 kg/m2. Frequency of SLR methods used was 54%BR, 25.6%NR, 10.8% BR + OS, and 9.8%OS. There were no differences in rate of leaks among SLR methods. Compared to NR, BR was associated with decreased rate of reoperations, overall bleeding, and major bleeding (p < 0.05) but prolonged operative time and length of stay (LOS) (p < 0.05). OS was associated with decreased overall bleeding (p < 0.05) but prolonged operative times and length of stay (p < 0.05) compared to NR. Compared to BR, OS was associated with increased operative times, LOS, and rates of post-operative ventilator use, pneumonia, and venous thrombosis (p < 0.05). Patients with bleeding were associated with lower rate of BR (56% vs 61%) and higher rate of NR (34% vs 28%) compared to patients with no bleeding. Bleeding was associated with a greater frequency of leaks (4.4% vs 0.3%), along with higher morbidity and mortality (p < 0.05). CONCLUSIONS: Of the reinforcement methods evaluated, BR and OS were both associated with decreased bleeding despite longer operative times. No method was found to significantly reduce incidence of leaks; however, bleeding was associated with increased incidence of leaks, morbidity, and mortality. The liberal use of SLR techniques is recommended for further optimization of patient outcomes after VSG.


Assuntos
Cirurgia Bariátrica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Cirurgia Bariátrica/efeitos adversos , Reoperação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Acreditação , Bases de Dados Factuais
13.
Annu Rev Pathol ; 18: 19-45, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36055769

RESUMO

African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in addition to loss of specificity and memory of the antibody response. The serum of humans contains an efficient trypanolytic factor, the membrane pore-forming protein apolipoprotein L1 (APOL1). In the two human-infective trypanosomes, specific parasite resistance factors inhibit APOL1 activity. In turn, many African individuals express APOL1 variants that counteract these resistance factors, enabling them to avoid sleeping sickness. However, these variants are associated with chronic kidney disease, particularly in the context of virus-induced inflammation such as coronavirus disease 2019. Vaccination perspectives are discussed.


Assuntos
COVID-19 , Tripanossomíase Africana , Humanos , Apolipoproteína L1/genética , Inflamação , Trypanosoma brucei rhodesiense/fisiologia , Tripanossomíase Africana/genética , Tripanossomíase Africana/parasitologia
14.
Front Cell Dev Biol ; 10: 851475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450294

RESUMO

The Trypanosoma (T) brucei life cycle alternates between the tsetse fly vector and the mammalian host. In the insect, T. brucei undergoes several developmental stages until it reaches the salivary gland and differentiates into the metacyclic form, which is capable of infecting the next mammalian host. Mammalian infectivity is dependent on expression of the metacyclic variant surface glycoprotein genes as the cells develop into mature metacyclics. The VEX complex is essential for monoallelic variant surface glycoprotein expression in T. brucei bloodstream form, however, initiation of expression of the surface proteins genes during metacyclic differentiation is poorly understood. To better understand the transition to mature metacyclics and the control of metacyclic variant surface glycoprotein expression we examined the role of VEX1 in this process. We show that modulating VEX1 expression leads to a dysregulation of variant surface glycoprotein expression during metacyclogenesis, and that following both in vivo and in vitro metacyclic differentiation VEX1 relocalises from multiple nuclear foci in procyclic cells to one to two distinct nuclear foci in metacyclic cells - a pattern like the one seen in mammalian infective bloodstream forms. Our data suggest a role for VEX1 in the metacyclic differentiation process and their capacity to become infectious to the mammalian host.

15.
mBio ; 13(2): e0384721, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35229632

RESUMO

In the mammalian host, Trypanosoma brucei is coated in a single-variant surface glycoprotein (VSG) species. Stochastic switching of the expressed VSG allows the parasite to escape detection by the host immune system. DNA double-strand breaks (DSB) trigger VSG switching, and repair via gene conversion results in an antigenically distinct VSG being expressed from the single active bloodstream-form expression site (BES). The single active BES is marked by VSG exclusion 2 (VEX2) protein. Here, we have disrupted monoallelic VSG expression by stably expressing a second telomeric VSG from a ribosomal locus. We found that cells expressing two VSGs contained one VEX2 focus that was significantly larger in size than the wild-type cells; this therefore suggests the ectopic VSG is expressed from the same nuclear position as the active BES. Unexpectedly, we report that in the double VSG-expressing cells, the DNA sequence of the ectopic copy is lost following a DSB in the active BES, despite it being spatially separated in the genome. The loss of the ectopic VSG is dependent on active transcription and does not disrupt the number or variety of templates used to repair a BES DSB and elicit a VSG switch. We propose that there are stringent mechanisms within the cell to reinforce monoallelic expression during antigenic variation. IMPORTANCE The single-cell parasite Trypanosoma brucei causes the fatal disease human African trypanosomiasis and is able to colonize the blood, fat, skin, and central nervous system. Trypanosomes survive in the mammalian host owing to a dense protective protein coat that consists of a single-variant surface glycoprotein species. Stochastic switching of one VSG for an immunologically distinct one enables the parasite to escape recognition by the host immune system. We have disrupted monoallelic antigen expression by expressing a second VSG and report that following DSB-triggered VSG switching, the DNA sequence of the ectopic VSG is lost in a transcription-dependent manner. We propose that there are strict requirements to ensure that only one variant antigen is expressed following a VSG switch, which has important implications for understanding how the parasite survives in the mammalian host.


Assuntos
Trypanosoma brucei brucei , Tripanossomíase Africana , Animais , Variação Antigênica , Conversão Gênica , Humanos , Mamíferos , Glicoproteínas de Membrana , Trypanosoma brucei brucei/genética
16.
BMC Vet Res ; 18(1): 45, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042521

RESUMO

BACKGROUND: Trypanosoma evansi is the leading infectious Trypanosoma spp. in camels (Camelus dromedarius) present in the Kingdom of Saudi Arabia (KSA) that could lead to extensive economic losses. The present study was aimed to assess the prevalence rate of T. evansi in Taif governorate, Makkah province, KSA using parasitological and molecular evaluations, and analyze their genetic relationship targeting internal transcribed spacer 1 (ITS1) and variable surface glycoprotein (VSG) genes. For evaluation, we have used 102 blood samples of camels obtained from three different regions in Taif. RESULTS: Results show a considerable prevalence rate of trypanosomosis 2/102 (2.0%) according to Giemsa-stained buffy coat smear, and 16/102 (15.7%) according to touchdown PCR. T. evansi (n = 10/102, 9.8%) was the main infectious species found in camels then T. vivax (n = 3/102, 2.9%). Mixed infections were detected in three camels with T. evansi, T. vivax, and T. congolense (n = 3/102, 2.9%). Regarding gender, the results indicate that female camels (11/66, 16.7%) show higher prevalence of Trypanosoma than males (5/36, 13.9%). Sequencing and phylogenetic analyses of ITS1 and VSG showed their relationships with T. evansi in other hosts from different countries. CONCLUSIONS: In our peer knowledge, it is the first time to report a research-based prevalence of trypanosomosis in the camels of Taif governorate, Makkah province, KSA.


Assuntos
Camelus/parasitologia , Trypanosoma , Tripanossomíase , Animais , Feminino , Masculino , Filogenia , Arábia Saudita , Trypanosoma/classificação , Trypanosoma/genética , Tripanossomíase/epidemiologia , Tripanossomíase/veterinária
17.
Math Biosci Eng ; 19(12): 12031-12057, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653985

RESUMO

The growth of distributed generation significantly reduces the synchronous generators' overall rotational inertia, causing large frequency deviation and leading to an unstable grid. Adding virtual rotational inertia using virtual synchronous generators (VSG) is a promising technique to stabilize grid frequency. Due to coupled nature of frequency and active output power in a grid-tied virtual synchronous generator (GTVSG), the simultaneous design of transient response and steady state error becomes challenging. This paper presents a duplex PD inertial damping control (DPDIDC) technique to provide active power control decoupling in GTVSG. The power verses frequency characteristics of GTVSG is analyzed emphasizing the inconsistencies between the steady-state error and transient characteristics of active output power. The two PD controllers are placed in series with the generator's inertia forward channel and feedback channel. Finally, the performance superiority of the developed control scheme is validated using a simulation based study.


Assuntos
Simulação por Computador , Eletrodos , Retroalimentação
18.
J Clin Med ; 10(21)2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34768422

RESUMO

Obese patients are at risk of dental erosion due to micronutrient deficiency, consumption of soft drinks, gastric reflux disease and vomiting. The present study evaluates the presence of dental erosion in obese patients before and after bariatric surgery using the BEWE (basic erosive wear examination) scoring system. A total of 62 patients with severe obesity were included in the analysis, 31 in the control group (without bariatric surgery) and 31 in the surgery group (after bariatric surgery). BEWE scores did not vary between groups. Vitamin D deficiency was detected in 19 patients in the control group and three in the surgery group (p < 0.001). The serum calcium and vitamin D values were significantly higher in the surgery group (p = 0.003, p < 0.001 consecutively). All patients after bariatric surgery showed compliance with supplements, including vitamin D and calcium daily. Patients after bariatric surgery were less likely to drink soft drinks regularly (p = 0.026). Obese patients, before or after bariatric surgery, are at risk for erosive dental wear. However, with sufficient education prior to surgery and consistent intake of vitamin and mineral supplements, significant erosive dental wear after bariatric surgery could be avoided. Regular dental examination should be included in the check-up and follow-up program.

19.
Front Cell Dev Biol ; 9: 744878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722526

RESUMO

In Trypanosoma brucei, genes are assembled in polycistronic transcription units (PTUs). Boundaries of PTUs are designated transcription start sites and transcription termination sites (TTSs). Messenger RNAs are generated by trans-splicing and polyadenylation of precursor RNAs, and regulatory information in the 3' un-translated region (UTR), rather than promoter activity/sequence-specific transcription factors, controls mRNA levels. Given this peculiar genome structure, special strategies must be utilized to control transcription in T. brucei. TTSs are deposition sites for three non-essential chromatin factors-two of non-canonical histone variants (H3v and H4v) and a DNA modification (base J, which is a hydroxyl-glucosyl dT). This association generated the hypothesis that these three chromatin marks define a transcription termination site in T. brucei. Using a panel of null mutants lacking H3v, H4v, and base J, here I show that H4v is a major sign for transcription termination at TTSs. While having a secondary function at TTSs, H3v is important for monoallelic transcription of telomeric antigen genes. The simultaneous absence of both histone variants leads to proliferation and replication defects, which are exacerbated by the J absence, accompanied by accumulation of sub-G1 population. Thus, I propose that the coordinated actions of H3v, H4v, and J provide compensatory mechanisms for each other in chromatin organization, transcription, replication, and cell-cycle progression.

20.
Obes Surg ; 31(11): 4939-4946, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34471996

RESUMO

BACKGROUND: Metabolic/bariatric surgery is a highly effective treatment for obesity and metabolic diseases. Serum glucagon, bile acids, and FGF-19 are key effectors of various metabolic processes and may play central roles in bariatric surgical outcomes. It is unclear whether these factors behave similarly after Roux-en-Y gastric bypass (RYGB) vs vertical sleeve gastrectomy (VSG). METHODS: Serum glucagon, bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA], deoxycholic acid [DCA]), and FGF-19 were analyzed in samples of fasting blood collected before bariatric surgery, on postoperative days 2 and 10, and at 3- and 6-month follow-up. RESULTS: From September 2016 to July 2017, patients with obesity underwent RYGB or VSG; 42 patients (RYGB n = 21; VSG n = 21) were included in the analysis. In the RYGB group, glucagon, CA, and CDCA increased continuously after surgery (p = 0.0003, p = 0.0009, p = 0.0001, respectively); after an initial decrease (p = 0.04), DCA increased significantly (p = 0.0386). Serum FGF-19 was unchanged. In the VSG group, glucagon increased on day 2 (p = 0.0080), but decreased over the 6-month study course (p = 0.0025). Primary BAs (CA and CDCA) decreased immediately after surgery (p = 0.0016, p = 0.0091) and then rose (p = 0.0350, p = 0.0350); DCA followed the curve of the primary BAs until it fell off at 6 months (p = 0.0005). VSG group serum FGF-19 trended upward. CONCLUSION: RYGB and VSG involve different surgical techniques and final anatomical configurations. Between postoperative day 2 and 6-month follow-up, RYGB and VSG resulted in divergent patterns of change in serum glucagon, bile acids, and FGF-19.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Ácidos e Sais Biliares , Fatores de Crescimento de Fibroblastos , Gastrectomia , Glucagon , Humanos , Obesidade Mórbida/cirurgia
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