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The properties of DNA that make it an effective genetic material also allow it to be ideal for programmed self-assembly. Such DNA-programmed assembly has been utilized to construct responsive DNA origami and wireframe nanoassemblies, yet replicating these hybrid nanomaterials remains challenging. Here we report a strategy for replicating DNA wireframe nanoassemblies using the isothermal ligase chain reaction lesion-induced DNA amplification (LIDA). We designed a triangle wireframe structure that can be formed in one step by ring-closing of its linear analog. Introducing a small amount of the wireframe triangle to an excess of the linear analog and complementary fragments, one of which contains a destabilizing abasic lesion, leads to rapid, sigmoidal self-replication of the wireframe triangle via cross-catalysis. Using the same cross-catalytic strategy we also demonstrate rapid self-replication of a hybrid wireframe triangle containing synthetic vertices as well as the self-replication of circular DNA. This work reveals the suitability of isothermal ligase chain reactions such as LIDA to self-replicate complex DNA architectures, opening the door to incorporating self-replication, a hallmark of life, into biomimetic DNA nanotechnology.
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DNA , Nanoestruturas , DNA/química , Nanoestruturas/química , Técnicas de Amplificação de Ácido Nucleico , Nanotecnologia/métodos , Replicação do DNA , Conformação de Ácido NucleicoRESUMO
The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges and the timing and mechanisms of several key transformations remain elusive. Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA-B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid sidechain required for biological activity. Here, we show that the mini-module MmpE performs a rare online (ACP-substrate) epoxidation and is integrated ('in-cis') into the polyketide synthase via a docking domain. A linear polyketide fragment with 6 asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0 and a previously unannotated ACP (MmpE_ACP). MmpE_ACP-bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA-B.
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The α1-acid glycoprotein (AGP) is an abundant blood plasma protein with important immunomodulatory functions coupled to endogenous and exogenous ligand-binding properties. Its affinity for many drug-like structures, however, means AGP can have a significant effect on the pharmokinetics and pharmacodynamics of numerous small molecule therapeutics. Staurosporine, and its hydroxylated forms UCN-01 and UCN-02, are kinase inhibitors that have been investigated at length as antitumour compounds. Despite their potency, these compounds display poor pharmokinetics due to binding to both AGP variants, AGP1 and AGP2. The recent renewed interest in UCN-01 as a cytostatic protective agent prompted us to solve the structure of the AGP2-UCN-01 complex by X-ray crystallography, revealing for the first time the precise binding mode of UCN-01. The solution NMR suggests AGP2 undergoes a significant conformational change upon ligand binding, but also that it uses a common set of sidechains with which it captures key groups of UCN-01 and other small molecule ligands. We anticipate that this structure and the supporting NMR data will facilitate rational redesign of small molecules that could evade AGP and therefore improve tissue distribution.
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Antineoplásicos/química , Orosomucoide/química , Estaurosporina/análogos & derivados , Cristalografia por Raios X , Humanos , Ligação Proteica , Domínios Proteicos , Estaurosporina/químicaRESUMO
BACKGROUND: The COVID-19 pandemic has resulted in serious mental health conditions, particularly among older adults. This research explored the prevalence of COVID-19-related anxiety and its associated factors among older adults residing in Bangladesh. METHODS: This cross-sectional study was conducted among 1,045 older Bangladeshi adults aged ≥ 60 years through telephone interviews in September 2021. A semi-structured interview schedule was used to collect data on participants' characteristics and COVID-19-related anxiety. The anxiety level was measured using the Bengali version of the five-point Coronavirus Anxiety Scale (CAS). A linear regression model explored the factors associated with COVID-19-related anxiety. RESULTS: Overall, the prevalence of COVID-19-related anxiety was 23.2%. The regression analysis revealed that the average COVID-19-related anxiety score was significantly higher among females (ß: 0.43, 95% CI: 0.05 to 0.81), and among those who faced difficulty getting medicine (ß: 0.57, 95% CI: 0.16 to 0.97), felt isolated (ß: 0.60, 95% CI: 0.24 to 0.95), and felt requiring additional care during the pandemic (ß: 0.53, 95% CI: 0.16 to 0.91). Alternatively, the average COVID-19-related anxiety score was significantly lower among those who were widowed (ß: -0.46, 95% CI: -0.87 to -0.04) and living distant from the health centre (ß: -0.48, 95% CI: -0.79 to -0.17). CONCLUSION: The findings of the present study suggest providing immediate psychosocial support package to the older adults, particularly females and those who are vulnerable to receive health and social care support during the COVID-19 pandemic in Bangladesh.
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COVID-19 , Feminino , Humanos , Idoso , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Bangladesh/epidemiologia , Ansiedade/epidemiologiaRESUMO
Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown. Herein we report the application of NMR spectroscopy, mass spectrometry, chemical probes and in vitro assays to establish the remaining steps of 9HN biosynthesis. These investigations reveal a complex interplay between a novel iterative or "stuttering" KS-AT didomain (MmpF), the multidomain module MmpB and multiple ACPs. This work has important implications for understanding the late-stage biosynthetic steps of mupirocin and will be important for future engineering of related trans-AT biosynthetic pathways (e.g. thiomarinol).
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Antibacterianos , Mupirocina , Antibacterianos/química , Proteína de Transporte de Acila/metabolismo , Policetídeo Sintases/metabolismoRESUMO
In order to achieve a nanometer-scale resolution in an x-ray microscopy system, a Gabor-type hologram was produced by eliminating the zero-order term of the object diffraction pattern. In this system, a Fresnel zone plate was used for strong illumination of an object, and the zero-order diffraction was physically eliminated by a center stop. An accurate phase plate of π/2 in the Zernike method was numerically created, and the phase-contrast image was realized. The theoretical resolution was 19.8 nm. We proved that a gold nanocube with a size of 50 nm can be reconstructed with the predicted resolution.
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Older adults residing in refugee settlements with unhealthy living environments, inadequate access to health care services, and limited psychosocial support are vulnerable to experience mental health problems jeopardizing their mental well-being. The present study aims to explore the mental well-being status and its socio-economic determinants among the older adults living in the Rohingya refugee camp in Bangladesh. This cross-sectional study was conducted among adults aged ≥ 60 residing in five sub-camps within the Rohingya refugee camp of Cox's Bazar, Bangladesh. Data were collected through face-to-face interviews conducted between November and December 2021. The 14-item Warwick-Edinburgh Mental Well-being Scale was used to assess mental well-being. A cumulated score was derived using the scale ranging from 14 to 70, with higher scores indicating greater levels of mental well-being. A generalized linear regression model was used to examine the socio-economic factors associated with the mental well-being of older adults. A total of 864 older adults participated in the study having a mean mental well-being score of 45.4. Regression analysis revealed that the difference in the logs of mental well-being score was expected to be significantly lower among participants aged 70-79 years (ß: - 1.661; 95% CI: - 2.750 to - 0.572; p = 0.003), aged ≥ 80 years (ß: - 3.198; 95% CI: - 5.114 to - 1.282; p = 0.001), and those with any non-communicable chronic conditions (ß: - 2.903; 95% CI: - 3.833 to - 1.974; p < 0.001) when compared to their counterparts. Conversely, the difference in the logs of mental well-being score was expected to be significantly higher among individuals with formal schooling (ß: 3.370, 95% CI: 1.855 to 4.886, p < 0.001) and those having additional income besides aid (ß: 1.629; 95% CI: 0.642 to 2.615; p = 0.001), compared to their respective counterparts. Our findings highlight the need to provide psychosocial assistance to older individuals, particularly those who live in large families, suffer from chronic diseases, and live in socio-economic deprivation.
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Saúde Mental , Campos de Refugiados , Refugiados , Fatores Socioeconômicos , Humanos , Bangladesh/epidemiologia , Masculino , Feminino , Idoso , Refugiados/psicologia , Pessoa de Meia-Idade , Estudos Transversais , Idoso de 80 Anos ou maisRESUMO
A quest was carried out to print on light weight lyocell knitted fabric with two mono-functional reactive dyes using pure guar gum (GG) or substituted guar gum (SGG) in combination with sodium alginate (Al) at different ratios. For each dyestuff, the print paste was prepared using mixed thickeners, namely GG/Al or SGA/Al at five different ratios. All samples were compared with the recipe containing pure sodium alginate. The empirical data show that the rheological behaviorisms of print paste-like viscosity and its other physical characteristics, such as paste add-on percentage (%) and penetration percentage (%), were dependent on the percentage of GG or SGG present in the thickener combination prepared with sodium Alginate. The combination of thickeners of these types also creates an impact on the final excellence of printed fabric, such as the colour yield, sharpness, stiffness of the fabric and the fastness of the colour. However, a few qualities are also dye dependent. The SGG/A combination gives a superior result when combining all the data with GG/A. Alginate with the small addition of SGG viz. the 80/20 or 60/40 mixture shows an excellent result in terms of printing characteristics. The thickener had no influential effect on the colour fastness rating.
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Several challenges need to be overcome when applying nucleic acids as therapeutic agents. We developed a new way to control the onset of the release of cholesterol-conjugated oligonucleotides with a simple, versatile, and cheap platform. Moreover, we combine the platform into a dual-release system that can release a hydrophobic drug with zero-order kinetics, followed by a rapid release of cholesterol-conjugated DNA.
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DNA , Oligonucleotídeos , Emulsões/química , DNA/química , ColesterolRESUMO
Background: Job satisfaction is one of the most important but least researched issues in the nursing profession in Bangladesh. This study aimed to investigate how workplace bullying and burnout are related to job satisfaction, as well as determine the factors that are associated with job satisfaction among Bangladeshi nurses. Methods: Data were collected from Bangladeshi registered nurses between February 26, 2021, and July 10, 2021, in this cross-sectional study. Bullying, burnout, and job satisfaction were measured with the Short Negative Acts Questionnaire [S-NAQ], the Burnout Measure-Short version (BMS), and the Short Index of Job Satisfaction (SIJS-5), respectively. The correlations between age, bullying, burnout, and job satisfaction were assessed using a Pearson's correlation test. In order to investigate the adjusted association of demographic characteristics, occupational variables, bullying, and burnout with job satisfaction, multiple linear regression models were fitted. Results: The study included 1,264 nurses (70.02% were female) with a mean age of 28.41 (±5.54) years. Job satisfaction was significantly negatively correlated with bullying and burnout (p < 0.001). According to the multiple linear regression models, the private-employed nurses had lower job satisfaction than the government-employed nurses (ß = -0.901, CI: -1.640 to -0.162). Compared to the nurses in the Dhaka division, the nurses in the Chattogram division (ß = 0.854, CI: 0.099 to 1.609) and other divisions (ß = 0.993, CI: 0.273 to 1.713) had higher job satisfaction. Nurses without sufficient equipment to manage patients (ß = -1.230, CI: -1.696 to -0.763), and nurses not paid on time (ß = -1.475, CI: -2.221 to -0.729) were predicted to have significantly lower job satisfaction. Nurses' job satisfaction levels were decreased with higher levels of workplace bullying (ß = -0.086, CI: -0.120 to -0.053), and burnout (ß = -1.040, CI: -1.242 to -0.838). Conclusions: Nurses' job satisfaction was correlated with workplace bullying and burnout. Moreover, insufficient professional support from the authorities predicted nurses' job satisfaction. Reducing the instances of bullying and burnout among nurses, as well as improving their working environment, are essential to increase job satisfaction. This is possible with the support of hospital management, policymakers, and government authorities.
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Background: Antibiotic resistance is a global challenge. Therefore, adhering to proper antibiotic administration protocols is essential to mitigating the problem. This study investigated the prevalence, and factors associated with, antibiotics administration without prescription by registered doctors in Bangladesh. Method: This cross-sectional survey was carried out among 1102 adults. The outcome variable was antibiotics administration without prescription. The exploratory variables included the those relating to sociodemographics, attitudes, and knowledge (antibiotic-treatable diseases, types of disease specification, and antimicrobial drugs specifications). Descriptive and inferential statistics were performed, with a p-value of 0.05 considered significant with a 95% confidence interval. Results: The prevalence of antibiotics administration without prescription was found to be 37.02%. Age was significantly associated with the administration of antibiotics without prescription. Those who had taken antibiotics in the previous 2 months reported a significantly higher prevalence of antibiotics administration without prescription. The participants' attitudes toward antibiotics and knowledge of antibiotic-treatable diseases, types of disease, and antimicrobial drugs were significantly associated with antibiotics administration without prescription. Conclusion: These findings may assist in facilitating relevant initiatives to improve the magnitude of antibiotics utilization without prescription, and mitigate the emergence of antibiotic resistance in Bangladesh.
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BACKGROUND: Depression is one of the most serious yet understudied issues among Bangladeshi nurses, bringing health dangers to this workforce. This study aimed to investigate how workplace violence (WPV), bullying, burnout, and job satisfaction are correlated with depression and identify the factors associated with depression among Bangladeshi nurses. METHODS: For this cross-sectional study, data were collected between February 26, 2021, and July 10, 2021 from the Bangladeshi registered nurses. The Workplace Violence Scale (WPVS), the Short Negative Acts Questionnaire [S-NAQ], the Burnout Measure-Short version (BMS), the Short Index of Job Satisfaction (SIJS-5), and the Patient Health Questionnaire (PHQ-9) were used to measure WPV, bullying, burnout, job satisfaction, and depression, respectively. Inferential statistics include Pearson's correlation test, t-test, one-way ANOVA test, multiple linear regression, and multiple hierarchal regression analyses were performed. RESULTS: The study investigated 1,264 nurses (70.02% female) with an average age of 28.41 years (SD = 5.54). Depression was positively correlated with WPV, bullying, and burnout and negatively correlated with job satisfaction (p <0.001). According to the multiple linear regression model, depression was significantly lower among nurses with diploma degrees (ß = -1.323, 95% CI = -2.149 to -0.497) and bachelor's degrees (ß = -1.327, 95% CI = -2.131 to- 0.523) compared to the nurses with master's degree. The nurses who worked extended hours (>48 hours) had a significantly higher depression score (ß = 1.490, 95% CI = 0.511 to 2.470) than those who worked ≤ 36 hours. Depression was found to be significantly higher among those who did not receive a timely salary (ß = 2.136, 95% CI = 1.138 to 3.134), rewards for good works (ß = 1.862, 95% CI = 1.117 to 2.607), and who had no training on WPV (ß = 0.895, 95% CI = 0.092 to 1.698). CONCLUSIONS: Controlling burnout, bullying, and workplace violence, as well as improving the work environment for nurses and increasing job satisfaction, are the essential indicators of reducing depression. This can be accomplished with integrative support from hospital executives, policymakers, and government officials.
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Bullying , Esgotamento Profissional , COVID-19 , Enfermeiras e Enfermeiros , Violência no Trabalho , Adulto , Esgotamento Profissional/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Satisfação no Emprego , Masculino , Pandemias , Reorganização de Recursos Humanos , Inquéritos e Questionários , Local de TrabalhoRESUMO
In this study, we aimed to facilitate the current diagnostic assessment of glaucoma by analyzing multiple features and introducing a new cross-sectional optic nerve head (ONH) feature from optical coherence tomography (OCT) images. The data (n = 100 for both glaucoma and control) were collected based on structural, functional, demographic and risk factors. The features were statistically analyzed, and the most significant four features were used to train machine learning (ML) algorithms. Two ML algorithms: deep learning (DL) and logistic regression (LR) were compared in terms of the classification accuracy for automated glaucoma detection. The performance of the ML models was evaluated on unseen test data, n = 55. An image segmentation pilot study was then performed on cross-sectional OCT scans. The ONH cup area was extracted, analyzed, and a new DL model was trained for glaucoma prediction. The DL model was estimated using five-fold cross-validation and compared with two pre-trained models. The DL model trained from the optimal features achieved significantly higher diagnostic performance (area under the receiver operating characteristic curve (AUC) 0.98 and accuracy of 97% on validation data and 96% on test data) compared to previous studies for automated glaucoma detection. The second DL model used in the pilot study also showed promising outcomes (AUC 0.99 and accuracy of 98.6%) to detect glaucoma compared to two pre-trained models. In combination, the result of the two studies strongly suggests the four features and the cross-sectional ONH cup area trained using deep learning have a great potential for use as an initial screening tool for glaucoma which will assist clinicians in making a precise decision.
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Aprendizado Profundo , Glaucoma , Estudos Transversais , Glaucoma/diagnóstico por imagem , Humanos , Projetos Piloto , Curva ROC , Células Ganglionares da Retina , Tomografia de Coerência Óptica/métodosRESUMO
Background: Telehealth is comprised of telecommunications and electronic information systems to support and maintain long-distance healthcare services. Although it has not been thoroughly explored, the intention of using the service among the general public is critical to its success. We investigated the factors associated with the intention to utilize telehealth services among the general population of Bangladesh. Methods: This cross-sectional study was conducted between May 22, 2021 and June 15, 2021 in Bangladesh, where the total number of participants was 1038. The Pearson chi-square test and Kruskal-Wallis H tests were used to examine the unadjusted relationship between the explanatory variables and the intention to use telehealth services. A multinomial logistic regression model was fitted to determine the adjusted association. Shapiro-Wilk tests were used to check the normality of continuous data. Data were processed and analyzed by software STATA-16. Results: The probability of utilizing the service increased significantly with increasing knowledge, perceived benefit, and predisposition levels among respondents. However, when perceived concern increased, the likelihood of utilizing the service dropped significantly. Age, marital status, educational status, profession, residence, and perceived health status were significantly associated with the participants' intention to utilize the telehealth service. Conclusions: The influencing aspects of telehealth service utilization should be recognized by the respective authorities. Possible activities to enhance usability among people are also recommended.
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Acessibilidade aos Serviços de Saúde , População do Sul da Ásia , Telemedicina , Humanos , Estudos Transversais , IntençãoRESUMO
Mupirocin is a clinically important antibiotic produced by Pseudomonas fluorescens NCIMB 10586 that is assembled by a complex trans-AT polyketide synthase. The polyketide fragment, monic acid, is esterified by a 9-hydroxynonanoic acid (9HN) side chain which is essential for biological activity. The ester side chain assembly is initialised from a 3-hydroxypropionate (3HP) starter unit attached to the acyl carrier protein (ACP) MacpD, but the fate of this species is unknown. Herein we report the application of NMR spectroscopy, mass spectrometry, chemical probes and in vitro assays to establish the remaining steps of 9HN biosynthesis. These investigations reveal a complex interplay between a novel iterative or "stuttering" KS-AT didomain (MmpF), the multidomain module MmpB and multiple ACPs. This work has important implications for understanding the late-stage biosynthetic steps of mupirocin and will be important for future engineering of related trans-AT biosynthetic pathways (e.g. thiomarinol).
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The development of safe and cost-effective methods for the treatment of dye polluted wastewater has been a great concern among researchers. Herein, we developed a nanocomposite (M3D-PAA-CCN) based on polyacrylic acid (PAA) crosslinked with magnetic 3D crosslinkers (M3D) and carboxylated cellulose nanocrystals (CCN), for the removal of cationic dyes from aqueous solutions. Acrylic-functionalized Fe3O4 nanoparticles were covalently linked to the polymer chains via the form of the 3D crosslinker to introduce magnetic properties into the as-synthesized nanocomposite. The addition of highly dispersive CCN reduced the gel-like properties of the nanocomposite and instead incorporated a diffusive nature, which was more desirable for adsorbents. The surface morphology of the nanocomposite was analyzed by FESEM and the size of the nanocomposite particles was found to be in the range of 60-90 nm. The chemical functionalities and compositions were determined by XPS, FTIR, and EDX analyses whereas TGA confirmed the thermal stability of M3D-PAA-CCN. The maximum adsorption capacity of the M3D-PAA-CCN (332 mg g-1) was measured higher than that of M3D-PAA (114 mg g-1) to a cationic methylene blue (MB) dye indicating the significant contribution of CCN. The adsorption capacity of the as-synthesized M3D-PAA-CCN was found to be highly pH-dependent and the adsorption capacity increased with the increase of pH owing to the greater negative charge as indicated by the higher zeta potential. The adsorption kinetics of MB on the composites was found to follow the pseudo-second-order model. The adsorption capacity was also investigated as a function of concentration to figure out the adsorption mechanism using Langmuir and Freundlich isotherm models. The Langmuir model fitted the adsorption process better as suggested by the relatively smaller nonlinear chi-square value obtained from the fitting parameters.
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Mupirocin, a commercially available antibiotic produced by Pseudomonas fluorescens NCIMB 10586, and thiomarinol, isolated from the marine bacterium Pseudoalteromonas sp. SANK 73390, both consist of a polyketide-derived monic acid homologue esterified with either 9-hydroxynonanoic acid (mupirocin, 9HN) or 8-hydroxyoctanoic acid (thiomarinol, 8HO). The mechanisms of formation of these deceptively simple 9HN and 8HO fatty acid moieties in mup and tml, respectively, remain unresolved. To define starter unit generation, the purified mupirocin proteins MupQ, MupS, and MacpD and their thiomarinol equivalents (TmlQ, TmlS and TacpD) have been expressed and shown to convert malonyl coenzyme A (CoA) and succinyl CoA to 3-hydroxypropionoyl (3-HP) or 4-hydroxybutyryl (4-HB) fatty acid starter units, respectively, via the MupQ/TmlQ catalyzed generation of an unusual bis-CoA/acyl carrier protein (ACP) thioester, followed by MupS/TmlS catalyzed reduction. Mix and match experiments show MupQ/TmlQ to be highly selective for the correct CoA. MacpD/TacpD were interchangeable but alternate trans-acting ACPs from the mupirocin pathway (MacpA/TacpA) or a heterologous ACP (BatA) were nonfunctional. MupS and TmlS selectivity was more varied, and these reductases differed in their substrate and ACP selectivity. The solution structure of MacpD determined by NMR revealed a C-terminal extension with partial helical character that has been shown to be important for maintaining high titers of mupirocin. We generated a truncated MacpD construct, MacpD_T, which lacks this C-terminal extension but retains an ability to generate 3-HP with MupS and MupQ, suggesting further downstream roles in protein-protein interactions for this region of the ACP.