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1.
Pharmacy (Basel) ; 12(3)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38921967

RESUMO

The primary goal of pharmacology teaching is to prepare medical students to prescribe medications both safely and efficiently. At the Utrecht University Medical School, pharmacology is integrated into the three-year bachelor's curriculum, primarily through large group sessions with limited interaction. A recent evaluation highlighted students' appreciation for pharmacology teaching, but students admitted to attending these teaching moments unprepared, resulting in passive learning. To address this, team-based learning (TBL) was implemented to facilitate learning through interaction, critical thinking, problem solving and reflection through six steps, from superficial to deeper cognitive learning. This study, conducted over two academic years, assessed students' perception and performance regarding TBL. Analysis of a digital questionnaire using a 5-point Likert scale showed high student satisfaction with TBL as a teaching methodology. However, confidence in pharmacology knowledge following TBL was moderate. TBL attendees outperformed non-attendees in pharmacology-related exam questions, indicating that TBL has a positive impact on student performance. We conclude that TBL is an engaging and effective method for pharmacology education, positively influencing student learning and performance. This method could be broadly applied for teaching pharmacology within the medical curriculum or other biomedical programs.

2.
BMC Med Educ ; 23(1): 833, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37936158

RESUMO

BACKGROUND: An inclusive academic environment is pivotal to ensure student well-being and a strong sense of belonging and authenticity. Specific attention for an inclusive learning environment is particularly important during a student's transition to higher education. At Utrecht University's Medical School, explorative interviews with students from minority groups indicated they did not always feel included during the orientation programme of their academic education. We, therefore, developed a bias awareness training with theoretical and practical components on diversity and inclusion for peer-mentors who are assigned to each first-year student at the start of university. METHODS: At the end of the orientation programme, we investigated the effectiveness of the training for two consecutive years using two measurements. Firstly, we investigated the behavioural changes in the peer-mentors through a (self-reporting) questionnaire. Additionally, we measured the perceived inclusion of the first-year students, divided into belonging and authenticity, using a validated questionnaire. RESULTS: Our results show that peer-mentors found the training useful and indicated it enabled them to create an inclusive atmosphere. Overall, students experienced a high level of inclusion during the orientation programme. After the first year, the bias training was adjusted based on the evaluations. This had a positive effect, as mentors felt they were significantly more able to provide an inclusive orientation in the second year of this study. In line with this, students experienced an increased level of authenticity specifically due to the peer-mentor in the second year as compared to the first. CONCLUSIONS: We conclude that training peer-mentors is an effective way to increase awareness and to ensure an inclusive atmosphere during the start of higher education.


Assuntos
Mentores , Estudantes de Medicina , Humanos , Grupo Associado , Grupos Minoritários , Faculdades de Medicina
3.
Sci Rep ; 11(1): 18774, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548600

RESUMO

Antimicrobial resistance has become one of the major threats to human health. Therefore, there is a strong need for novel antimicrobials with new mechanisms of action. The kingdom of fungi is an excellent source of antimicrobials for this purpose because it encompasses countless fungal species that harbor unusual metabolic pathways. Previously, we have established a library of secondary metabolites from 10,207 strains of fungi. Here, we screened for antimicrobial activity of the library against seven pathogenic bacterial strains and investigated the identity of the active compounds using ethyl acetate extraction, activity-directed purification using HPLC fractionation and chemical analyses. We initially found 280 antimicrobial strains and subsequently identified 17 structurally distinct compounds from 26 strains upon further analysis. All but one of these compounds, berkchaetoazaphilone B (BAB), were known to have antimicrobial activity. Here, we studied the antimicrobial properties of BAB, and found that BAB affected energy metabolism in both prokaryotic and eukaryotic cells. We conclude that fungi are a rich source of chemically diverse secondary metabolites with antimicrobial activity.


Assuntos
Benzopiranos/farmacologia , Metabolismo Energético/efeitos dos fármacos , Pigmentos Biológicos/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Ascomicetos/química , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana
4.
Virology ; 436(1): 191-200, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23260111

RESUMO

The mRNAs encoding the Rev and Env proteins of simian immunodeficiency virus (SIV) are unique because upstream translation start codons are present that may modulate the expression of these viral proteins. We previously reported the regulatory effect of a small upstream open reading frame (ORF) on Rev and Env translation. Here we study this mechanism in further detail by modulating the strength of the translation signals upstream of the open reading frames in subgenomic reporters. Furthermore, the effects of these mutations on SIV gene expression and viral replication are analyzed. An intricate regulatory mechanism is disclosed that allows the virus to express a balanced amount of these two proteins.


Assuntos
Códon de Iniciação , Produtos do Gene env/genética , Produtos do Gene rev/genética , Fases de Leitura Aberta , Vírus da Imunodeficiência Símia/genética , Linhagem Celular , Regulação Viral da Expressão Gênica , Genes env , Genes rev , Células HEK293 , Humanos , Mutação , Biossíntese de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vírus da Imunodeficiência Símia/metabolismo
5.
J Virol ; 86(22): 12362-71, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22951834

RESUMO

The mRNAs encoding the Rev and Env proteins of simian immunodeficiency virus (SIV) are unique because upstream translation start codons are present that may modulate the expression of these viral proteins. This is true for the regular mRNAs, but we also report novel mRNA splicing variants that encode up to five upstream AUG (uAUG) codons. Their influence on Rev and Env translation was measured by mutational inactivation in reporter constructs and in the SIVmac239 strain. An intricate regulatory mechanism was disclosed that allows the virus to express a balanced amount of these two proteins. This insight also allows the design of vector constructs that efficiently express these proteins.


Assuntos
Códon de Iniciação , Produtos do Gene env/genética , Produtos do Gene rev/genética , Genoma Viral , Vírus da Imunodeficiência Símia/genética , Processamento Alternativo , Códon , Genes Reporter , Células HEK293 , Humanos , Leucócitos Mononucleares/virologia , Modelos Genéticos , Mutação , Fases de Leitura Aberta , Splicing de RNA , RNA Mensageiro/metabolismo , Análise de Sequência de DNA
6.
J Gen Virol ; 93(Pt 10): 2279-2289, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22815271

RESUMO

Tat has a pivotal role in human and simian immunodeficiency virus (HIV and SIV) replication because it stimulates transcription by binding to the trans-activator response (TAR) element. In addition, several other Tat functions have been proposed. Most studies have focused on HIV-1 Tat and much less is known about SIV Tat. An SIVmac239 variant was constructed previously in which the Tat-TAR transcription mechanism is functionally replaced by the doxycycline-inducible Tet-On gene expression mechanism (SIV-rtTA). In this study, SIV-rtTA variants were used to analyse the functions of SIV Tat. It was shown that Tat-minus SIV-rtTA variants replicated efficiently in PM1 T-cells, ruling out an additional essential Tat function. Nevertheless, replication was suboptimal in other cells, and evolutionary pressure to repair Tat expression was documented. It was demonstrated that SIV-rtTA required Tat for optimal gene expression, despite the absence of the Tat-TAR axis. This Tat effect was lost upon replacement of the long terminal repeat promoter region by a non-related promoter. These results indicate that Tat can activate SIV transcription via TAR RNA and U3 DNA elements but has no other essential function in replication in cultured cells. The experiments were limited to cell lines and PBMCs, and did not exclude an accessory Tat function under specific conditions or in vivo.


Assuntos
Vírus da Imunodeficiência Símia/genética , Transativadores/genética , Transcrição Gênica , Replicação Viral/genética , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética , Células Cultivadas , Expressão Gênica , Células HEK293 , Repetição Terminal Longa de HIV , Humanos , Regiões Promotoras Genéticas , RNA Viral/genética , Vírus da Imunodeficiência Símia/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo
7.
J Gen Virol ; 93(Pt 9): 2017-2027, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22647372

RESUMO

A novel genetic approach for the control of virus replication was used for the design of a conditionally replicating human immunodeficiency virus (HIV) variant, HIV-rtTA. HIV-rtTA gene expression and virus replication are strictly dependent on the presence of a non-toxic effector molecule, doxycycline (dox), and thus can be turned on and off at will in a graded and reversible manner. The in vivo replication capacity, pathogenicity and genetic stability of this HIV-rtTA variant were evaluated in a humanized mouse model of haematopoiesis that harbours lymphoid and myeloid components of the human immune system (HIS). Infection of dox-fed BALB Rag/γc HIS (BRG-HIS) mice with HIV-rtTA led to the establishment of a productive infection without CD4(+) T-cell depletion. The virus did not show any sign of escape from dox control for up to 10 weeks after the onset of infection. No reversion towards a functional Tat-transactivating responsive (TAR) RNA element axis was observed, confirming the genetic stability of the HIV-rtTA variant in vivo. These results demonstrate the proof of concept that HIV-rtTA replicates efficiently in vivo. HIV-rtTA is a promising tool for fundamental research to study virus-host interactions in vivo in a controlled fashion.


Assuntos
Linfócitos T CD4-Positivos/virologia , Doxiciclina/metabolismo , Regulação Viral da Expressão Gênica , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Replicação Viral , Animais , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , HIV-1/genética , Humanos , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout
8.
J Gen Virol ; 91(Pt 9): 2374-80, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20484560

RESUMO

Human immunodeficiency virus type 1 (HIV-1) is classified into different phylogenetic subtypes, with subtype C representing more than half of the novel infections globally. However, there are relatively few subtype C envelopes available for study. We amplified 18 unique env genes from 13 patients who were infected with subtype C HIV-1 in six African countries and in Scotland to create replication-competent viruses. These envelopes are phylogenetically diverse across the subtype C spectrum, and have on average more N-linked glycosylation sites and slightly longer variable loops than previously described C envelopes. We found that CCR3 coreceptor usage is less prevalent in subtype C than in subtype B viruses, and these envelopes have varied sensitivity to neutralization. The subtype C chimeric viruses generated in this study will be useful for evaluating the breadth of neutralizing antibodies and other entry inhibitors.


Assuntos
Genes env , HIV-1/classificação , HIV-1/genética , África , Clonagem Molecular , Glicosilação , Antígenos HIV/química , Antígenos HIV/genética , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/fisiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Testes de Neutralização , Filogenia , Receptores CCR3/fisiologia , Receptores de HIV/fisiologia , Escócia , Produtos do Gene env do Vírus da Imunodeficiência Humana/química , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
9.
J Biol Chem ; 284(14): 9153-9, 2009 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-19164282

RESUMO

Repellents of the maize pathogen Ustilago maydis are involved in formation of hydrophobic aerial hyphae and in cellular attachment. These peptides, called Rep1-1 to Rep1-11, are encoded by the rep1 gene and result from cleavage of the precursor protein Rep1 during passage of the secretion pathway. Using green fluorescent protein as a reporter, we here show that rep1 is expressed in filaments and not in the yeast form of U. maydis. In situ hybridization localized rep1 mRNA in the apex of the filament, which correlates with the expected site of secretion of the repellents into the cell wall. We also produced a synthetic peptide, Rep1-1. This peptide reduced the water surface tension to as low as 36 mJ m(-2). In addition, it formed amyloid-like fibrils as was shown by negative staining, by thioflavin T fluorescence, and by x-ray diffraction. These fibrils were not soluble in SDS but could be dissociated with trifluoroacetic acid. The repellents in the hyphal cell wall had a similar solubility and also stained with thioflavin T, strongly indicating that they are present as amyloid fibrils. However, such fibrils could not be observed at the hyphal surface. This can be explained by the fact that the Rep1-1 filaments decrease in length at increasing concentrations. Taken together, we have identified the second class of fungal proteins that form functional amyloid-like filaments at the hyphal surface.


Assuntos
Amiloide/metabolismo , Proteínas Fúngicas/metabolismo , Fragmentos de Peptídeos/metabolismo , Ustilago/metabolismo , Ustilago/patogenicidade , Amiloide/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Microscopia Eletrônica , Fragmentos de Peptídeos/genética , Ustilago/genética , Ustilago/ultraestrutura
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