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Applied and Environmental Microbiology Jun 2024Although functional studies on carbohydrate-binding module (CBM) have been carried out extensively, the role of tandem CBMs in the enzyme containing multiple catalytic...
UNLABELLED
Although functional studies on carbohydrate-binding module (CBM) have been carried out extensively, the role of tandem CBMs in the enzyme containing multiple catalytic domains (CDs) is unclear. Here, we identified a multidomain enzyme (Lc25986) with a novel modular structure from lignocellulolytic bacterial consortium. It consists of a mannanase domain, two CBM65 domains (LcCBM65-1/LcCBM65-2), and an esterase domain. To investigate CBM function and domain interactions, full-length Lc25986 and its variants were constructed and used for enzymatic activity, binding, and bioinformatic analyses. The results showed that LcCBM65-1 and LcCBM65-2 both bind mannan and xyloglucan but not cellulose or β-1,3-1,4-glucan, which differs from the ligand specificity of reported CBM65s. Compared to LcCBM65-2, LcCBM65-1 showed a stronger ligand affinity and a preference for acetylation sites. Both CBM65s stimulated the enzymatic activities of their respective neighboring CDs against acetylated mannan, but did not contribute to the activities of the distal CDs. The time course of mannan hydrolysis indicated that the full-length Lc25986 was more effective in the complete degradation of mixed acetyl/non-acetyl substrates than the mixture of single-CD mutants. When acting on complex substrates, LcCBM65-1 not only improved the enzymatic activity of the mannanase domain, but also directed the esterase domain to the acetylated polysaccharides. LcCBM65-2 adopted a low affinity to reduce interference with the catalysis of the mannanase domain. These results demonstrate the importance of CBMs for the synergism between the two CDs of a multidomain enzyme and suggest that they contribute to the adequate degradation of complex substrates such as plant cell walls.
IMPORTANCE
Lignocellulolytic enzymes, particularly those of bacterial origin, often harbor multiple carbohydrate-binding modules (CBMs). However, the function of CBM multivalency remains poorly understood. This is especially true for enzymes that contain more than one catalytic domain (CD), as the interactions between CDs, CBMs, and CDs and CBMs can be complex. Our research demonstrates that homogeneous CBMs can have distinct functions in a multimodular enzyme. The tandem CBMs coordinate the CDs in catalytic conflict through their differences in binding affinity, ligand preference, and arrangement within the full-length enzyme. Additionally, although the synergism between mannanase and esterase is widely acknowledged, our study highlights the benefits of integrating the two enzymes into a single entity for the degradation of complex substrates. In summary, these findings enhance our understanding of the intra-synergism of a multimodular enzyme and emphasize the significance of multiple CBMs in this context.
PubMed: 38940565
DOI: 10.1128/aem.00888-24 -
Frontiers in Public Health 2024The issue of low consumption among rural households in China has a longstanding history, and the experience of infectious diseases may exacerbate the existing challenges...
OBJECTIVE
The issue of low consumption among rural households in China has a longstanding history, and the experience of infectious diseases may exacerbate the existing challenges in fostering consumption growth. However, studies that characterize the impact of infectious diseases on household consumption are limited in China. This study aims to explore rural household consumption responses to infectious diseases post-assessment, and identify the underlying mechanisms.
METHODS
A total of 1,539 rural households from China Family Panel Studies (CFPS) datasets of 2014, 2016, 2018, and 2020 were recruited as the study sample. The presence of infectious disease experience was employed as the independent variable and household consumption as the dependent variable. A panel fixed effects (FE) regression model was initially employed to identify the influence of infectious disease experiences on rural household consumption. The instrumental variable (IV) method was used to address potential endogeneity between independent and dependent variables. Robustness checks such as Propensity Score Matching (PSM) test were employed to ensure the reliability of the findings.
RESULTS
The results reveal a statistically significant negative impact of infectious disease experiences on consumption over time, becoming no more significant at around 7-9 years post-disaster. This effect leads to more pronounced consumption deprivation for households with limited health insurance coverage and heightened healthcare resource constraints. The mechanism test indicates that infectious disease experiences affect the consumption levels of rural households through channels that include income constraints, the crowding-out of healthcare expenditure, and risk perception, with the precautionary savings motive acting as a moderator. Furthermore, the diminishing effect of infectious diseases on individual consumption surpasses that of natural disasters. Temporal discrepancy is observed in the impacts of infectious and chronic disease shocks on household consumption. The accumulation of liquid assets emerges as an effective strategy for households to mitigate the impact of infectious disease shocks.
CONCLUSION
The findings underscore the importance of integrating short- and long-term policies to bolster consumption capacity, strategically allocate inter-regional medical resources, and fortify the resilience of rural households against economic risks.
Topics: Humans; China; Rural Population; Family Characteristics; Communicable Diseases; Female; Male; Adult; Middle Aged
PubMed: 38932772
DOI: 10.3389/fpubh.2024.1390432 -
Pharmaceutics May 2024According to the latest World Health Organization (WHO) report, an estimated 10.6 million people were diagnosed with tuberculosis (TB) in 2022, and 1.30 million died. A... (Review)
Review
According to the latest World Health Organization (WHO) report, an estimated 10.6 million people were diagnosed with tuberculosis (TB) in 2022, and 1.30 million died. A major concern is the emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains, fueled by the length of anti-TB treatment and HIV comorbidity. Innovative anti-TB agents acting with new modes of action are the only solution to counteract the spread of resistant infections. To escape starvation and survive inside macrophages, has evolved to become independent of the host by synthesizing its own amino acids. Therefore, targeting amino acid biosynthesis could subvert the ability of the mycobacterium to evade the host immune system, providing innovative avenues for drug discovery. The aim of this review is to give an overview of the most recent progress in the discovery of amino acid biosynthesis inhibitors. Among the hits discovered over the past five years, tryptophan (Trp) inhibitors stand out as the most advanced and have significantly contributed to demonstrating the feasibility of this approach for future TB drug discovery. Future efforts should be directed at prioritizing the chemical optimization of these hits to enrich the TB drug pipeline with high-quality leads.
PubMed: 38931847
DOI: 10.3390/pharmaceutics16060725 -
Sensors (Basel, Switzerland) Jun 2024A novel design of a MEMS (Micro-Electromechanical System) capacitive accelerometer fabricated by surface micromachining, with a structure enabling precise...
A novel design of a MEMS (Micro-Electromechanical System) capacitive accelerometer fabricated by surface micromachining, with a structure enabling precise auto-calibration during operation, is presented. Precise auto-calibration was introduced to ensure more accurate acceleration measurements compared to standard designs. The standard mechanical structure of the accelerometer (seismic mass integrated with elastic suspension and movable plates coupled with fixed plates forming a system of differential sensing capacitors) was equipped with three movable detection electrodes coupled with three fixed electrodes, thus creating three atypical tunneling displacement transducers detecting three specific positions of seismic mass with high precision, enabling the auto-calibration of the accelerometer while it was being operated. Auto-calibration is carried out by recording the accelerometer indication while the seismic mass occupies a specific position, which corresponds to a known value of acting acceleration determined in a pre-calibration process. The diagram and the design of the mechanical structure of the accelerometer, the block diagram of the electronic circuits, and the mathematical relationships used for auto-calibration are presented. The results of the simulation studies related to mechanical and electric phenomena are discussed.
PubMed: 38931800
DOI: 10.3390/s24124018 -
Materials (Basel, Switzerland) Jun 2024This paper presents the results of an experimental modal analysis of a beam covered by polymer materials used as a passive vibration isolation. The main aim of this...
This paper presents the results of an experimental modal analysis of a beam covered by polymer materials used as a passive vibration isolation. The main aim of this study was to determine the damping properties of selected viscoelastic materials. In order to check the damping properties of tested materials, an experimental modal analysis, with the use of an electrodynamic vibration system, was performed. In this study, four kinds of specimens were considered. In the first step of the work, the beam made out of aluminum alloy was investigated. Afterwards, a cantilever beam was covered with a layer of bitumen-based material acting as a damper. This method is commonly known as a free layer damping treatment (FLD). In order to increase the damping capabilities, the previous configuration was improved by fixing a thin aluminum layer directly to the viscoelastic core. Such a treatment is called constrained layer damping (CLD). Subsequently, another polymer (butyl rubber) in the CLD configuration was tested for its damping properties. As a result of the performed experimental modal analysis, the frequencies of resonant vibrations and their corresponding amplitudes were obtained. The experimental results were used to quantitatively evaluate the damping properties of tested materials.
PubMed: 38930389
DOI: 10.3390/ma17123021 -
Semergen Jun 2024The basis of COPD maintenance treatment is the long-acting bronchodilators and the inhaled corticosteroids. Faced with the recent modifications in the clinical practice... (Review)
Review
The basis of COPD maintenance treatment is the long-acting bronchodilators and the inhaled corticosteroids. Faced with the recent modifications in the clinical practice guidelines, we have carried out a review of studies that contrast the various therapeutic alternatives and pharmacological agents within each category, with the fundamental purpose of shedding light on which of these options prove to be more effective. Triple therapy stands out as essential in poorly controlled patients or with an eosinophilic phenotype, surpassing dual therapy. However, among the combinations of LAMA/LABA or LAMA/LABA/IC, no drug is observed to be superior in the reviewed evidence. Although triple therapies include corticosteroids, there does not appear to be a significant increase in side effects or pneumonia. Regarding monotherapy with LAMA, no significant differences are seen between the drugs, but in dual therapy with LABA/IC, the budesonide/formoterol combination seems to offer better control than fluticasone/salmeterol.
PubMed: 38925076
DOI: 10.1016/j.semerg.2024.102284 -
Plant Biology (Stuttgart, Germany) Jun 2024YABBY genes encode specific TFs of seed plants involved in development and formation of leaves, flowers, and fruit. In the present work, genome-wide and expression...
YABBY genes encode specific TFs of seed plants involved in development and formation of leaves, flowers, and fruit. In the present work, genome-wide and expression analyses of the YABBY gene family were performed in six species of the Fragaria genus: Fragaria × ananassa, F. daltoniana, F. nilgerrensis, F. pentaphylla, F. viridis, and F. vesca. The chromosomal location, synteny pattern, gene structure, and phylogenetic analyses were carried out. By combining RNA-seq data and RT-qPCR analysis we explored specific expression of YABBYs in F. × ananassa and F. vesca. We also analysed the promoter regions of FaYABBYs and performed MeJA application to F. × ananassa fruit to observe effects on gene expression. We identified and characterized 25 YABBY genes in F. × ananassa and six in each of the other five species, which belong to FIL/YAB3 (YABBY1), YAB2 (YABBY2), YAB5 (YABBY5), CRC, and INO clades previously described. Division of the YABBY1 clade into YABBY1.1 and YABBY1.2 subclades is reported. We observed differential expression according to tissue, where some FaYABBYs are expressed mainly in leaves and flowers and to a minor extent during fruit development of F. × ananassa. Specifically, the FaINO genes contain jasmonate-responsive cis-acting elements in their promoters which may be functional since FaINOs are upregulated in F. × ananassa fruit under MeJA treatment. This study suggests that YABBY TFs play an important role in the development- and environment-associated responses of the Fragaria genus.
PubMed: 38924267
DOI: 10.1111/plb.13656 -
British Journal of Clinical Pharmacology Jun 2024Long-acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre-exposure HIV prophylaxis are being rolled out in a multitude of... (Review)
Review
Long-acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre-exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake 'traditional' pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug-drug interactions (DDIs) with frequent concomitant medications in African settings. Relevant co-medications were identified from the WHO 2021 List of Essential Medicines. All original human and physiologically based pharmacokinetic studies published in English on PubMed, discussing DDIs with LAI cabotegravir and rilpivirine prior to April 2023, were reviewed. The Liverpool HIV interaction database was also reviewed (https://www.hiv-druginteractions.org/checker). LAI cabotegravir and rilpivirine have half-lives of 6-12 and 13-28 weeks, respectively. Cabotegravir is primarily metabolized by UDP-glucuronyltransferase (UGT)-1A1 and rilpivirine by cytochrome P450 (CYP)-3A4. LAI cabotegravir and rilpivirine themselves exhibit low risk of perpetrating interactions with co-medications as they do not induce or inhibit the major drug metabolizing enzymes. However, they are victims of DDIs relating to the induction of their metabolizing enzymes by concomitantly administered medication. Noteworthy contraindicated co-medications include rifamycins, carbamazepine, phenytoin, flucloxacillin and griseofulvin, which induce CYP3A4 and/or UGT1A1, causing clinically significant reduced concentrations of rilpivirine and/or cabotegravir. In addition to virologic failure, subtherapeutic concentrations resulting from DDIs can lead to emergent drug resistance. Clinicians should be aware of potential DDIs and counsel people receiving LAI cabotegravir/rilpivirine appropriately to minimize risk.
PubMed: 38923554
DOI: 10.1111/bcp.16154 -
Experimental & Applied Acarology Jun 2024Viticulture is characterized by substantial pesticide applications, impacting natural enemies. New pest control strategies and management of plant diversity into...
Viticulture is characterized by substantial pesticide applications, impacting natural enemies. New pest control strategies and management of plant diversity into agrosystems acting as reservoirs of natural enemies are assumed to limit pesticide use. Various studies support this hypothesis but gaps exist on the effect of diversification on Phytoseiidae mites, generalist predators reported as prevalent and efficient natural enemies in vineyards. This study focuses on the effect of cover crop management (no cover crop, spontaneous cover crops with or without agroforestry) and grape variety (resistant cv. Artaban and cv. Syrah) on predatory mites and prey communities, in a newly planted experimental vineyard in South-East France. Samplings were carried out three times a year on vine, cover crops, and co-planted trees. Phytoseiidae, Tydeiidae, Eriophyidae mites and thrips were characterized. Nine Phytoseiidae species were identified on vine, the main ones being Kampimodromus aberrans, Typhlodromus exhilaratus, Phytoseius finitimus and Euseius gallicus. Kampimodromus aberrans was prevalent on the cv. Syrah, highlighting a strong effect of variety. The low unexpected effect of system management observed outcome could be due to several factors, such as the experimental plot size or the influence of vine stress on Phytoseiidae communities in vines with cover crops. All phytoseiid species present on vine were identifed at least once on cover crops and co-planted trees, suggesting their potential role as reservoirs. Further studies should be performed investigating the evolution of communities in this newly-planted experimental system, as well as potential differences in trophic network interactions.
PubMed: 38922518
DOI: 10.1007/s10493-024-00938-z -
Microbiology Spectrum Jun 2024Acetic acid bacteria are used in many industrial processes such as the production of vinegar, vitamin C, the antidiabetic drug miglitol, and various artificial...
Acetic acid bacteria are used in many industrial processes such as the production of vinegar, vitamin C, the antidiabetic drug miglitol, and various artificial flavorings. These industrially important reactions are primarily carried out by an arsenal of periplasmic-facing membrane-bound dehydrogenases that incompletely oxidize their substrates and shuttle electrons directly into the respiratory chain. Among these dehydrogenases, GOX in was predicted to be a pyrroloquinoline quinone-dependent dehydrogenase of unknown function. However, after multiple analysis by a number of labs, no dehydrogenase activity has been detected. Reanalysis of GOX1969 sequence and structure reveals similarities to BamB, which functions as a subunit of the β-barrel assembly machinery complex that is responsible for the assembly of β-barrel outer membrane proteins in Gram-negative bacteria. To test if the physiological function of GOX1969 is similar to BamB in , we introduced the gene into an ∆ mutant. Growth deficiencies in the ∆ mutant were restored when was expressed on the plasmid pGox1969. Furthermore, increased membrane permeability conferred by deletion was restored upon expression, which suggests a direct link between GOX1969 and a role in maintaining outer membrane stability. Together, this evidence strongly suggests that GOX1969 is functionally acting as a BamB in . As such, functional information on uncharacterized genes will provide new insights that will allow for more accurate modeling of acetic acid bacterial metabolism and further efforts to design rational strains for industrial use.IMPORTANCE is an industrially important member of the acetic acid bacteria. Experimental characterization of putative genes is necessary to identify targets for further engineering of rational acetic acid bacteria strains that can be used in the production of vitamin C, antidiabetic compounds, artificial flavorings, or novel compounds. In this study, we have identified an undefined dehydrogenase GOX1969 with no known substrate and defined structural similarities to outer membrane biogenesis protein BamB in K12. Furthermore, we demonstrate that GOX1969 is capable of complementing knockout phenotypes in K12. Taken together, these findings enhance our understanding of physiology and expand the list of potential targets for future industrial strain design.
PubMed: 38916353
DOI: 10.1128/spectrum.01060-24