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Because a finite set of measurements is limited in the amount of spectral content it can represent, the reconstruction process from discrete samples is inherently band-limited. In the case of 1D sampling using ideal measurements, the maximum bandwidth of regular and irregular sampling is well known using Nyquist and Gröchenig sampling theorems and lemmas, respectively. However, determining the appropriate reconstruction bandwidth becomes difficult when considering 2D sampling geometries, samples with variable apertures, or signal to noise ratio limitations. Instead of determining the maximum bandwidth a priori, we derive an inverse method to simultaneously reconstruct a signal and determine its effective bandwidth. This inverse method is equivalent to incrementally computing a band-limited inverse using a frequency-constrained QR decomposition (FQR). Comparisons between reconstruction results using FQR and QR decompositions illustrate how FQR is less sensitive to noisy measurement errors, but it is more sensitive to high-frequency components. These methods are particularly useful in the reconstruction of remote sensing images from such as microwave radiometers and scatterometers.

Variable aperture sampling reconstruction matrices have a history of being computationally intensive due to the need to compute a full matrix inverse. In the field of remote sensing, several spaceborne radiometers and scatterometers, which have irregular sampling and variable apertures, use iterative techniques to reconstruct measurements of the Earth’s surface. However, many of these iterative techniques tend to over-amplify noise features outside the reconstructable bandwidth. Because the reconstruction of discrete samples is inherently bandlimited, solving a bandlimited inverse can focus on recovering signal features and prevent the over-amplification of noise outside the signal bandwidth. To approximate a bandlimited inverse, we apply bandlimited constraints to several well-known iterative reconstruction techniques: Landweber iteration, additive reconstruction technique (ART), Richardson–Lucy iteration, and conjugate gradient descent. In the context of these iterative techniques, we derive an iterative method for inverting variable aperture samples, taking advantage of the regular and irregular content of variable apertures. We find that this iterative method for variable aperture reconstruction is equivalent to solving a bandlimited conjugate gradient descent algorithm.

The most used viscosity-modifying agents (VMAs) in 3D concrete printing (3DCP) are typically in powder form, which may pose challenges in dispersion and handling due to their low concentration and dust generation. This study explores the viability of using microfibrillated cellulose (MFC) in suspension and paste forms as a VMA in 3D-printable Portland cement mortars. The performance of these developed mortars was compared to a cement mortar containing hydroxypropyl methylcellulose (HPMC) in powder form. The mortars containing MFC in suspension and paste forms showed slightly higher workability, mechanical strength, and denser microstructure than those with HPMC. The MFC samples showed a higher viscosity and yield stress than the ones containing HPMC. A large-scale concrete 3D printer was used for the printability test. The HPMC mortars showed slightly superior extrudability and printability; however, the shape stability was inferior to that of the MFC mortars. The compressive strength of the 3D-printed samples was 40% lower compressive strength than the mold-cast samples; however, the flexural strength was comparable. Overall, the MFC in paste form outperformed the other VMAs studied here, providing better shape stability, while maintaining acceptable printability.

This review highlights some established and some more contemporary mechanisms responsible for heart failure (HF)-induced skeletal muscle wasting and weakness. We first describe the effects of HF on the relationship between protein synthesis and degradation rates, which determine muscle mass, the involvement of the satellite cells for continual muscle regeneration, and changes in myofiber calcium homeostasis linked to contractile dysfunction. We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment. Overall, HF causes multiple impairments related to autophagy, anabolic-catabolic signaling, satellite cell proliferation, and calcium homeostasis, which together promote fiber atrophy, contractile dysfunction, and impaired regeneration. Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF, the effects of satellite cell dynamics remain poorly explored.

A novel registered practical nurse-led video conferencing approach using PIECESTM for team-based care planning was developed to engage family/care partners in the care of older adults. The objectives were to: (a) explore the experiences of older adults and family/care partners in collaborating in implementation science research in long-term care (LTC); (b) identify facilitators and barriers to engaging older adults and family/care partners in implementation science research; and (c) share recommendations to support the engagement of older adults and family/care partners in research. A qualitative descriptive design was used. Two older adults and two family/care partners from two Canadian LTC homes were involved in the research. Data, comprised of interviews with older adults and family/care partners, and notes from research team meetings, were analyzed using thematic analysis. Older adults and family/care partners perceived they made valuable contributions to the research project. They expressed beliefs that care delivery required improvements for older adults with responsive behaviours in LTC, which served as motivation to participate in the research project. Facilitating factors included the support of familiar LTC staff for older adults to engage in research activities and understanding the value of PIECES. A barrier to engagement for older adults was research terminology and processes described during team meetings. This research highlighted taken-for-granted factors in a collaborative research endeavour with older adults and family/care partners. One-on-one interaction, follow-up 'reporting' and presence of familiar LTC staff are needed to support meaningful engagement of older adults and family/care partners in research. Experience Framework This article is associated with the Innovation & Technology lens of The Beryl Institute Experience Framework (https://theberylinstitute.org/experience-framework/). Access other PXJ articles related to this lens. Access other resources related to this lens.

Objective This scoping review aimed to summarize current knowledge about the implementation, impacts, facilitators and barriers of virtual team-based care planning for older persons in formal care settings (e.g. home and community, primary, long-term and acute care). Methods The Joanna Briggs Institute (JBI) methodology was used. The Arksey and O’Malley and Levac, Colquhoun, and O’Brien methodologies provided additional frameworks. Databases accessed included PubMed, EMBASE, CINAHL, AgeLine, PsycInfo and Scopus. Reference lists of selected articles and grey literature retrieved through Google and Google Scholar were also reviewed. Three researchers screened titles, abstracts and conducted full-text reviews. Extracted data were mapped in a table and analysed for summative themes. Older persons and family partners assisted in interpreting findings based on their lived experiences. Results A total of 27 studies were included. Virtual team-based care planning led to many positive outcomes for older persons (e.g. decreased depression, reduced falls and improved medication management) and their families (e.g. reduced caregiver stress and improved caregiving skills). Only four studies reported the involvement of older persons and/or families in virtual team-based care planning. Multiple barriers to adopting virtual team-based care planning were found including lack of education/training for older persons and families in using technology. Conclusion Despite the multiple advantages that virtual team-based care planning offers for older persons and families, it is important to ensure that this care can be offered to all. There is a need to ensure that health equity is addressed to promote access to care and respond to social determinants of health.

The majority of ships are coated with antifouling paint. These coatings can fail to completely protect from fouling due to mismatches between paint type and duty cycle, the presence of biocide tolerant fouling organisms, improperly applied, old or damaged paint, etc. Grooming antifouling coatings can provide a solution. Five commercially available antifouling coatings were applied to panels. Half of the replicates were groomed weekly, the other half were immersed and allowed to freely foul, undisturbed. Photographs were taken and panels were visually assessed monthly. Over the period of two years, all the undisturbed panels became fouled with a diverse community of macrofouling organisms including encrusting and arborescent bryozoans, barnacles, tube worms, oysters, tunicates and more. The groomed panels remained clean of macrofouling for an extended period of time, up to two years depending on the coating. Cover of biofilm was also low on groomed panels. Grooming was effective at maintaining different antifouling paints clear of macrofouling and decreasing cover of biofilms for up to two years of immersion.

Biofilms are conglomerates of cells, water, and extracellular polymeric substances which can lead to various functional and financial setbacks. As a result, there has been a drive towards more environmentally friendly antifouling methods, such as the use of ultraviolet C (UVC) radiation. When applying UVC radiation, it is important to understand how frequency, and thus dose, can influence an established biofilm. This study compares the impacts of varying doses of UVC radiation on both a monocultured biofilm consisting of Navicula incerta and field-developed biofilms. Both biofilms were exposed to doses of UVC radiation ranging from 1626.2 mJ/cm2 to 9757.2 mJ/cm2 and then treated with a live/dead assay. When exposed to UVC radiation, the N. incerta biofilms demonstrated a significant reduction in cell viability compared to the non-exposed samples, but all doses had similar viability results. The field biofilms were highly diverse, containing not only benthic diatoms but also planktonic species which may have led to inconsistencies. Although they are different from each other, these results provide beneficial data. Cultured biofilms provide insight into how diatom cells react to varying doses of UVC radiation, whereas the real-world heterogeneity of field biofilms is useful for determining the dosage needed to effectively prevent a biofilm. Both concepts are important when developing UVC radiation management plans that target established biofilms.

The application of a proactive grooming program to manage the fouling control coatings applied to ship hulls provides an opportunity to address the climate crisis, invasive species and the discharge of biocides into the marine environment. A large percentage of the total power required to propel a ship is to overcome the viscous drag created between the hull and the water. The powering penalty due to increases in coating roughness and the development of biofouling are well documented. In addition, poorly maintained fouling control coatings may lead to the transportation of invasive species. In-water hull cleaning is therefore an important part of ship operations; however, this is typically implemented as a reactive measure when fouling reaches a critical level and requires powerful machinery which damages the coatings, creates unwanted discharge and in many locations the discharge will require capture and disposal. Ship hull grooming is being developed as a proactive method to manage fouling control coatings that will ensure that they are maintained in a smooth and fouling free condition, there is no transport of invasive species or excessive discharge of material that occurs during cleaning. This manuscript will summarize the findings of many years of research and development.

Introduction COVID-19 has necessitated greater adoption of virtual care (eg, telephone (audio), videoconference) delivery models. Virtual care provides opportunities for innovative practice in care planning with older persons and meaningful family engagement by synchronously involving multiple care providers. Nevertheless, there remains a paucity of summarising evidence regarding virtual team-based care planning for older persons. The purpose of this scoping review is to summarise evidence on the utilisation of virtual team-based care planning for older persons in formal care settings. Specifically, (1) what has been reported in the literature on the impact or outcomes of virtual team-based care planning? (2) What are the facilitators and barriers to implementation?Methods and analysis This scoping review will follow a rigorous and well-established methodology by the Joanna Briggs Institute, supplemented by the Arksey & O’Malley and Levac, Colquhoun, & O’Brien frameworks. A three-step search strategy will be used to conduct a search on virtual team-based care planning for older persons in formal care settings. Keywords and index terms will be identified from an initial search in PubMed and AgeLine, and used to conduct the full search in the databases PubMed, EMBASE, CINAHL, AgeLine, PsycInfo and Scopus. Reference lists of included articles and grey literature retrieved through Google and Google Scholar will also be reviewed. Three researchers will screen titles and abstracts, and will conduct full-text review for inclusion. Extracted data will be mapped in a table.Ethics and dissemination Research ethics approval is not required for data collection from publicly accessible information. Findings will be presented at conferences, submitted for open-access publication in a peer-reviewed journal and made accessible to multiple stakeholders. The scoping review will summarise the literature on virtual team-based care planning for the purpose of informing the implementation of a virtual PIECES™ intervention (Physical/Intellectual/Emotional health, Capabilities, Environment, and Social).

Objective. This meta-analysis examines the relationship between early-life obesity and risk of colorectal cancer (CRC) in adulthood. Methods. A systematic search of Google Scholar, PubMed, and reference data was conducted. Fifteen relevant studies were identified and meta-analyzed, for men and women separately. A random-effects model was used to compare the multivariable-adjusted relative risks (RR) of overall and subsite-specific CRC to the highest versus lowest categories of body mass index (BMI) in early life. Meta-regression was performed on factors that may have contributed to between-study heterogeneity. Results. High early-life BMI was associated with a 39% increased risk of CRC in adult men (RR = 1.39, 95%CI = 1.20 – 1.62, P < 0.0001) and a 19% increased risk of CRC in adult women (RR = 1.19, 95%CI = 1.06 – 1.35, P = 0.004). No statistically significant heterogeneity was identified in meta-regression according to tumor subsite (RR = 1.06, 95%CI = 0.97 – 1.17, RR = 1.08, 95%CI = 0.99 – 1.18 for male and female proximal colon cancer; RR = 1.51, 95%CI = 1.22 – 1.87, RR = 1.08, 95%CI = 0.98 – 1.19 for male and female distal colon cancer; and RR = 1.39, 95%CI = 1.1 – 1.77, RR = 1.51, 95%CI = 0.94 – 2.03 for male and female rectal cancer) or other factors, including age of BMI assessment, self-reported or measured BMI, and adjustment for smoking. Conclusions. The results suggest that high early-life BMI is associated with increased risk of CRC in adulthood. Further studies should investigate adult CRC risk in early-life obese individuals from non-Western countries and the underlying mechanisms by which early-life adiposity may influence CRC pathogenesis.

A survey was conducted to explore the perception of intensive care registrars on the impact of activities outside the intensive care unit (ICU), particularly in medical emergency teams, on their training and the care of patients. An anonymous mail-out survey was sent to 356 trainees registered with the Joint Faculty of Intensive Care Medicine, half of whom were determined to be involved in ICU duties. No patients were involved and respondents participated voluntarily. The main outcome measures were barriers and predictors of satisfaction with ICU training. One-hundred-and-thirty-six (38%) trainees responded. Seventy-eight percent had participated in a medical emergency team, of whom 99% of respondents stated the medical emergency team included an ICU registrar but rarely (3%) an ICU consultant. Sixty-six percent of respondents reported that medical emergency team involvement had a positive effect on training but 77% reported little or no supervision of team duties. While trainees did not believe they spent too much time performing medical emergency team duties, the time spent on medical emergency teams at night, when ICU staffing levels are at their lowest, was the same as during the day. Serious concern was expressed about the negative impact of medical emergency team activities on their ability to care for ICU patients and the additional stress on ICU medical and nursing staff Overall, ICU trainees regarded participation in a medical emergency team as positive on training and on patient care in wards, but other results have resource implications for the provision of clinical emergency response systems, care of patients in ICUs and the training of the future intensive care workforce. [ABSTRACT FROM AUTHOR]

To address the increase in overweight and obesity among mothers and children in sub-Saharan Africa, an understanding of the factors that drive their food consumption is needed. We hypothesized food consumption in Malawi is driven by a combination of factors, including season, food accessibility (area of residence, convenience of purchasing food, female autonomy), food affordability (household resources, food expenditures, household food insecurity), food desirability (taste preferences, body size preferences), demographics, and morbidity. Participants in Lilongwe and Kasungu Districts were enrolled across three types of mother-child dyads: either the mother (n = 120), child (n = 80), or both (n = 74) were overweight. Seven-day dietary intake was assessed using a quantitative food frequency questionnaire during the dry and rainy seasons. Drivers associated with intake of calories, macronutrients, and 11 food groups at p

Biofouling is problematic for the shipping industry and can lead to functional and financial setbacks. One possible means of biofouling prevention is the use of ultraviolet-C (UVC) light. Previous studies have investigated UVC with marine coatings, but the synergistic effect with color and surface material, specifically reflectance, has yet to be determined. This study comprised three parts: UVC and color (red vs. white), UVC and reflectance (stainless steel vs. polycarbonate), and UVC and exposure intervals (weekly intervals and 10 min intervals). There was no variance in the biofouling communities for colored surfaces when exposed to 254 nm UVC. Reflectance studies demonstrated that the surface material plays a role in biofouling settlement. Stainless steel panels had significantly greater macrofouling settlement than polycarbonate, specifically among encrusting bryozoan, tubeworms, and tunicate communities. Panels of both surface materials exposed to indirect UVC significantly differed from controls and those exposed directly to UVC. Exposure intervals were also found to reduce biofouling settlement especially with long frequent intervals (i.e., 10 min/day). UVC can be utilized on various colored surfaces and different surface types, but the effectiveness in preventing biofouling is ultimately determined by the duration and frequency of UVC exposure.

A stereodivergent total synthesis has been executed based on the plausibly misassigned structure of the unusual marine hydrindane mucosin (1). The topological connectivity of the four contiguous all-carbon stereocenters has been examined by selective permutation on the highlighted core. Thus, capitalizing on an unprecedented stereofacial preference of the cis-fused bicycle[4.3.0]non-3-ene system when a Michael acceptor motif is incorporated, copper-mediated conjugate addition furnished a single diastereomer. Cued by the relative relationship reported for the appendices in the natural product, the resulting anti-adduct was elaborated into a probative target structure 1*.

Three different protocols for the syntheses of hydroxyalkylnitramines are presented and compared. Safety issues regarding the synthesis of nitramines are also discussed.

Abstract Background Surgical site infection (SSI) is a common complication following abdominal surgery. It is associated with considerable morbidity and mortality, and its management results in significant cost to health services within both primary and secondary care. Some surgeons believe that the use of a wound-edge protection device may reduce the incidence of SSI. Whilst there is some encouraging evidence showing that such devices may lead to a reduction in SSI, there are no controlled trials of sufficient size or quality to support their routine use. Methods/Design 750 patients will be recruited from around 20 surgical units within the United Kingdom. Patients undergoing laparotomy through any major abdominal incision for any indication, elective or emergency, are eligible. Patients under the age of 18, those undergoing a laparoscopic assisted procedure or who have undergone laparotomy within the previous 3 months, and those who are unable to give informed consent will be excluded. Patients will be randomised (1:1 ratio) to the use of a wound-edge protection device or no wound-edge protection device during surgery. Follow up will consist of blinded clinical wound reviews at 5-7 days and 30-33 days postoperatively with a self-completed questionnaire covering the intervening period. Quality of life questionnaires will be completed prior to surgery and at the subsequent wound review points and information on resource usage will also be captured. The primary outcome measure is SSI within 30 days of surgery. Secondary outcomes include the impact of the degree of wound contamination, patient comorbidity, and operative characteristics on the efficacy of a wound-edge protection device in reducing SSI and whether the use of a wound-edge protection device has an effect on health-related quality of life or length of hospital stay and is cost-effective. Discussion Rossini is the first multicentre observer-blinded randomised controlled trial of sufficient size and quality to establish whether the use of a wound-edge protection device in adult patients undergoing abdominal surgery leads to a lower rate of SSI. The results of this study will be used to inform current surgical practice and may potentially benefit patients undergoing surgery in the future. Trial registration number Current Controlled Trials ISRCTN: ISRCTN40402832

Peptidoglycan synthesis is an essential driver of bacterial growth and division. The final steps of this crucial process involve the activity of the SEDS family glycosyltransferases that polymerize glycan strands and the class B penicillin-binding protein (bPBP) transpeptidases that cross-link them. While many bacteria encode multiple bPBPs to perform specialized roles during specific cellular processes, some bPBPs can play redundant roles that are important for resistance against certain cell wall stresses. Our understanding of these compensatory mechanisms, however, remains incomplete. Endospore-forming bacteria typically encode multiple bPBPs that drive morphological changes required for sporulation. The sporulation-specific bPBP, SpoVD, is important for synthesizing the asymmetric division septum and spore cortex peptidoglycan during sporulation in the pathogen Clostridioides difficile . Although SpoVD catalytic activity is essential for cortex synthesis, we show that it is unexpectedly dispensable for SpoVD to mediate asymmetric division. The dispensability of SpoVD's catalytic activity requires the presence of its SEDS partner, SpoVE, and is facilitated by another sporulation-induced bPBP, PBP3. Our data further suggest that PBP3 interacts with components of the asymmetric division machinery, including SpoVD. These findings suggest a possible mechanism by which bPBPs can be functionally redundant in diverse bacteria and facilitate antibiotic resistance.

Of the approximately 10 million cases of Mycobacterium tuberculosis ( Mtb ) infections each year, over 10% are resistant to the frontline antibiotic isoniazid (INH). INH resistance is predominantly caused by mutations that decrease the activity of the bacterial enzyme KatG, which mediates the conversion of the pro-drug INH to its active form INH-NAD. We previously discovered an inhibitor of Mtb respiration, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a collection of INH-resistant mutants to INH through an unknown mechanism. To investigate the mechanism of action of C10, we exploited the toxicity of high concentrations of C10 to select for resistant mutants. We discovered two mutations that confer resistance to the disruption of energy metabolism and allow for the growth of Mtb in high C10 concentrations, indicating that growth inhibition by C10 is associated with inhibition of respiration. Using these mutants as well as direct inhibitors of the Mtb electron transport chain, we provide evidence that inhibition of energy metabolism by C10 is neither sufficient nor necessary to potentiate killing by INH. Instead, we find that C10 acts downstream of INH-NAD synthesis, causing Mtb to become particularly sensitive to inhibition of the INH-NAD target, InhA, without changing the concentration of INH-NAD or the activity of InhA, the two predominant mechanisms of potentiating INH. Our studies revealed that there exists a vulnerability in Mtb that can be exploited to render Mtb sensitive to otherwise subinhibitory concentrations of InhA inhibitor.IMPORTANCEIsoniazid (INH) is a critical frontline antibiotic to treat Mycobacterium tuberculosis ( Mtb ) infections. INH efficacy is limited by its suboptimal penetration of the Mtb -containing lesion and by the prevalence of clinical INH resistance. We previously discovered a compound, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a set of INH-resistant mutants to INH. Resistance is typically mediated by katG mutations that decrease the activation of INH, which is required for INH to inhibit the essential enzyme InhA. Our current work demonstrates that C10 re-sensitizes INH-resistant katG -hypomorphs without enhancing the activation of INH. We furthermore show that C10 causes Mtb to become particularly vulnerable to InhA inhibition without compromising InhA activity on its own. Therefore, C10 represents a novel strategy to curtail the development of INH resistance and to sensitize Mtb to sub-lethal doses of INH, such as those achieved at the infection site., Competing Interests: The authors have no competing financial interests to declare but acknowledge that C.L.S. and F.A. have ownership in the company that licenses C10, QureTech Bio AB, and therefore may financially benefit if the company is successful in marketing its product, and the Patti laboratory has a research collaboration agreement with Agilent Technologies.

Gregory Harrison is a bacteriologist researching essential pathways in bacteria as potential therapeutic targets. In this mSphere of Influence article, he reflects on a series of studies that employ complementary genetic approaches to define the crucial role of AsmA-family proteins in transporting phospholipids between the inner and outer membranes of Gram-negative bacteria. The authors of these three studies identify this family of lipid transporters through the means of bacterial genetics, answering a long-standing question in bacterial physiology, and serving as a reminder that a well-designed genetic strategy can go a long way in uncovering new biology., Competing Interests: The author declares no conflict of interest.

Mycobacterium tuberculosis ( Mtb ) drug resistance poses an alarming threat to global tuberculosis control. We previously reported that C10 , a ring-fused thiazolo-2-pyridone, inhibits Mtb respiration, blocks biofilm formation, and restores the activity of the antibiotic isoniazid (INH) in INH-resistant Mtb isolates. This discovery revealed a new strategy to address INH resistance. Expanding upon this strategy, we identified C10 analogues with improved potency and drug-like properties. By exploring three heterocycle spacers (oxadiazole, 1,2,3-triazole, and isoxazole) on the ring-fused thiazolo-2-pyridone scaffold, we identified two novel isoxazoles, 17h and 17j . 17h and 17j inhibited Mtb respiration and biofilm formation more potently with a broader therapeutic window, were better potentiators of INH-mediated inhibition of an INH-resistant Mtb mutant, and more effectively inhibited intracellular Mtb replication than C10 . The (-)17j enantiomer showed further enhanced activity compared to its enantiomer and the 17j racemic mixture. Our potent second-generation C10 analogues offer promise for therapeutic development against drug-resistant Mtb .

Of the approximately 10 million cases of Mycobacterium tuberculosis ( Mtb ) infections each year, over 10% are resistant to the frontline antibiotic isoniazid (INH). INH resistance is predominantly caused by mutations that decrease the activity of the bacterial enzyme KatG, which mediates conversion of the pro-drug INH to its active form INH-NAD. We previously discovered an inhibitor of Mtb respiration, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a collection of INH-resistant mutants to INH through an unknown mechanism. To investigate the mechanism of action of C10, we exploited the toxicity of high concentrations of C10 to select for resistant mutants. We discovered two mutations that confer resistance to the disruption of energy metabolism and allow for growth of Mtb in high C10 concentrations, indicating that growth inhibition by C10 is associated with inhibition of respiration. Using these mutants as well as direct inhibitors of the Mtb electron transport chain, we provide evidence that inhibition of energy metabolism by C10 is neither sufficient nor necessary to potentiate killing by INH. Instead, we find that C10 acts downstream of INH-NAD synthesis, causing Mtb to become particularly sensitive to inhibition of the INH-NAD target, InhA, without changing the concentration of INH-NAD or the activity of InhA, the two predominant mechanisms of potentiating INH. Our studies revealed that there exists a vulnerability in Mtb that can be exploited to render Mtb sensitive to otherwise subinhibitory concentrations of InhA inhibitor., Competing Interests: Competing Interests The authors have no competing financial interests to declare, but acknowledge that C.L.S. and F.A. have ownership in the company QureTech Bio AB that licenses C10 and, therefore, may financially benefit if the company is successful in marketing its product, and the Patti laboratory has a research collaboration agreement with Agilent Technologies.

Treatment of Mycobacterium tuberculosis ( Mtb) infections is particularly arduous. One challenge to effectively treating tuberculosis is that drug efficacy in vivo often fails to match drug efficacy in vitro. This is due to multiple reasons, including inadequate drug concentrations reaching Mtb at the site of infection and physiological changes of Mtb in response to host derived stresses that render the bacteria more tolerant to antibiotics. To more effectively and efficiently treat tuberculosis, it is necessary to better understand the physiologic state of Mtb that promotes drug tolerance in the host. Towards this end, multiple studies have converged on bacterial central carbon metabolism as a critical contributor to Mtb drug tolerance. In this review, we present the evidence that changes in central carbon metabolism can promote drug tolerance, depending on the environment surrounding Mtb . We posit that these metabolic pathways could be potential drug targets to stymie the development of drug tolerance and enhance the efficacy of current antimicrobial therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Samuels, Wang, Harrison, Valenta and Stallings.)

Jasmonate (JA) is an important hormone involved in regulating diverse responses to environmental factors as well as growth and development, and its signalling is influenced by other hormones such as ethylene (ET). However, our understanding of the regulatory relationship between the JA and ET signalling pathways is limited. In this study, we isolated an Arabidopsis JA-hypersensitive mutant, jah3 (jasmonate hypersensitive3)-1. Map-based cloning revealed that the JAH3 gene corresponds to At4g16535. JAH3 encodes a protein of unknown function whose amino acid sequence has similarity to leukocyte receptor cluster-like protein. The mutation in jah3-1 is caused by a single nucleotide change from A to T at position 220 of 759 bp. Using CRISPR-Cas9, we generated a second allele, jah3-2, that encodes a truncated protein. Both of these loss-of-function alleles resulted in hypersensitivity to JA, ET-induced root growth inhibition, and accelerated dark-induced senescence. Double mutant analyses employing coronatine insensitive 1 (coi1) and ethylene insensitive 3 (ein3) mutants (jah3 coi1 and jah3 ein3) demonstrated that the hypersensitive phenotypes of the jah3 mutants are mediated by JA and ET signalling components COI1 and EIN3. Therefore, we propose that JAH3 is a negative regulator of both JA and ET signalling., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Mycobacterium tuberculosis ( Mtb ), the causative agent of tuberculosis (TB), remains a leading cause of death due to infection in humans. To more effectively combat this pandemic, many aspects of TB control must be developed, including better point of care diagnostics, shorter and safer drug regimens, and a protective vaccine. To address all these areas of need, better understanding of the pathogen, host responses, and clinical manifestations of the disease is required. Recently, the application of cutting-edge technologies to the study of Mtb pathogenesis has resulted in significant advances in basic biology, vaccine development, and antibiotic discovery. This leaves us in an exciting era of Mtb research in which our understanding of this deadly infection is improving at a faster rate than ever, and renews hope in our fight to end TB. In this review, we reflect on what is known regarding Mtb pathogenesis, highlighting recent breakthroughs that will provide leverage for the next leaps forward in the field.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a major health threat listed among the top 10 causes of death worldwide. Treatment of multidrug-resistant Mtb requires use of additional second-line drugs that prolong the treatment process and result in higher death rates. Our team previously identified a 2-pyridone molecule (C10) that blocks tolerance to the first-line drug isoniazid at C10 concentrations that do not inhibit bacterial growth. Here, we discovered that the genes rv3160c and rv3161c are highly induced by C10, which led us to investigate them as potential targets. We show that Rv3160c acts as a TetR-like transcriptional repressor binding to a palindromic sequence located in the rv3161c promoter. We also demonstrate that C10 interacts with Rv3160c, inhibiting its binding to DNA. We deleted the rv3161c gene, coding for a putative oxygenase, to investigate its role in drug and stress sensitivity as well as C10 activity. This Δrv3161c strain was more tolerant to isoniazid and lysozyme than wild type Mtb. However, this tolerance could still be blocked by C10, suggesting that C10 functions independently of Rv3161c to influence isoniazid and lysozyme sensitivity.