Linear Pathway Research Articles

Immunomodulatory metabolites in IgE-mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.

The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown. To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT. Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes. Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10-20) and linoleic acid derivatives (q = 3.8 × 10-5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10-8), eicosanoids (q = 7.9 × 10-7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU. We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.

A Project-Led Framework for Coach Development in English Men’s Professional Football: A Premier League Case Study

Coach education and development programmes are central to the professional development experiences of sport coaches. Typically, these programmes are structured and sequenced in a linear pathway, and present an opportunity for certification which can be a prerequisite to practice and/or employment. Increasingly, as learning becomes viewed as part of a coach’s lifeworld, versus simply as a means to an end, education and development provision is beginning to reflect this. This article introduces and explores the Coach Development Institute Programme, part of the Premier League’s Elite Coaching Plan, which seeks to improve the quality of football coaching in English boys’/men’s football by engaging coaches in a 2-year work-based learning opportunity. Built around a core of project-based learning and assessment, coaches are supported as they examine a series of meaningful performance problems in their unique practice environments. Through this work, we demonstrate how theories, concepts, and principles from the adult education and assessment as learning literature might work as they are applied in a coach education and development context. With such sparsity of case-based examples like this within the peer-reviewed literature, we intend that our contribution could inform, promote dialogue, and raise questions about authentically supporting coaches beyond a minimum standard of practice.

Decision-making pathways for contraceptive use among refugee and host populations in Adjumani district, Uganda; an exploratory study

IntroductionContraceptive use is known to have a positive impact on maternal and child health outcomes; however, its use is still low in low-income countries, especially among people in humanitarian situations. This study explored decision-making processes towards the use of contraceptives by people in humanitarian situations to inform program design and uptake.MethodsA qualitative exploratory study was conducted among women of reproductive age (15–49 years) and men (15–60 years) living in three refugee settlements of Pagirinya, Nyumanzi, and Mirieyi and the surrounding host communities in Adjumani district, Uganda. Data were collected using 49 in-depth interviews (IDIs), 11 Key Informant Interviews (KIIs,) and 20 Focus Group Discussions (FGDs). Inductive thematic analysis was done with the aid of Atlas ti. Version 14.ResultsWe found that the decision-making processes entailed linear and nonlinear internalized cognitive and contextual processes involving four dynamic pathways. In the linear pathway, participants reported starting with 1) idea inception, 2) followed by cognitive processing, 3) consultation, and 4) decision-making for contraceptive use. The complex linear pathway happened when participants did not go through consultation but went straight to decision-making. However, participants who followed the non-linear pathway repeatedly went back to cognitive processing. Some women after consultation, or those already using and those not using contraceptives, decided to go back to cognitive processing to reconsider their current positions. This study found that some women who were not using contraceptives ended up using, while some who were using contraception ended up dropping out.ConclusionsThis study showed dynamic decision-making processes involving both internal and external environments as triggers to decision-making for contraceptive use. Interventions to increase contraceptive use should target both users and significant others who influence the decision to use particularly among refugees.Trial registrationThis study was registered by Makerere University School of Public Health Higher Degrees Research and Ethic Committee (HDREC) #188 and approved by Uganda National Council of Science and Technology on 15th/7/2021, Registration number—SS809ES.

Evolution of the sex-determination gene Doublesex within the termite lineage

The molecular mechanism of sex determination has long been considered conserved in insects. However, recent studies of hemimetabolous insects have challenged this notion. One notable example is termites. In Reticulitermes speratus, a homolog of sex determination gene, Doublesex (RsDsx), exhibits characteristics that are distinct from those of other insects, including sister-group cockroaches. It comprises a single exon, contains only doublesex/mab-3 DNA-binding domain (DM) but lacks a conserved oligomerization domain (OD), and exhibits transcriptional activity only in males. To investigate whether these characteristics are widespread within the termite lineage, we identified Dsx homologs in three different families. The absence of the conserved OD sequences was observed in all termite species examined, whereas the number of exons and expression patterns between sexes varied among families. Particularly, distinctive differences in Dsx were found in species from the Archotermopsidae and Kalotermitidae, both of which have a linear caste developmental pathway. Our findings indicate that diversification of Dsx structure and expression patterns may have contributed to ecological diversification, such as caste developmental pathways, within the termite lineage.

A linear ontogeny accounts for the development of naive, memory and tumour-infiltrating regulatory T cells in mice.

Foxp3 + Regulatory T cells (Treg) are a subset of CD4 + T cells that play critical functions in maintaining tolerance to self antigens and suppressing autoimmunity, regulating immune responses to pathogens and have a role in the pathophysiology of anti-tumoural immunity. Treg ontogeny is complex since they are generated following recognition of self antigens in the thymus during normal T cell development (thymic Treg), but are also induced from mature conventional T cells when activated by foreign antigen with appropriate additional cues (inducible Treg). How these distinct ontogenic pathways contribute to the maintenance and function of the mature Treg compartment in health and disease remains unclear. Here, we use a combination of fate mapping approaches in mice to map the ontogeny of Treg subsets throughout life and estimate rates of production, loss and self-renewal. We find that naive and effector/memory (EM) Treg subsets exhibit distinct dynamics but are both continuously replenished by de novo generation throughout life. Using an inducible Foxp3-dependent Cre fate reporter system, we show that naive Treg and not conventional T cells, are the predominant precursors of EM Treg in adults. Tonic development of new EM Treg is not influenced by foreign antigens from commensals, rather suggesting a role for self recognition. To investigate the ontogeny of Treg development in malignant disease, we used the same fate reporter systems to characterise the Treg infiltrate of three different model tumours. In all three cases, we found that Treg derived from pre-existing, EM Treg. Together, these results reveal a predominantly linear pathway of Treg development from thymic origin to EM Treg associated with pathophysiology of malignant disease, that is driven by self antigen recognition throughout.

Association of early menarche with breast tumor molecular features and recurrence

BackgroundEarly menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear.MethodsWe profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952).ResultsEarly menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferation (e.g. Myc, PI3K/AKT/mTOR, cell cycle), oxidative stress (e.g. oxidative phosphorylation, unfolded protein response), and inflammation (e.g. pro-inflammatory cytokines IFNα\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha$$\\end{document} and IFNγ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document}). Replication in TCGA confirmed these trends. Early menarche was associated with significantly higher PAM50 proliferation scores (β = 0.082 [0.02–0.14]), odds of aggressive molecular tumor subtypes (basal-like, OR = 1.84 [1.18–2.85] and HER2-enriched, OR = 2.32 [1.46–3.69]), and PAM50 risk of recurrence score (β = 4.81 [1.71–7.92]). Our NHS-derived early menarche gene expression signature was significantly associated with worse 10-year disease-free survival in METABRIC (N = 952, HR = 1.58 [1.10–2.25]).ConclusionsEarly menarche is associated with more aggressive molecular tumor characteristics and its gene expression signature within tumors is associated with worse 10-year disease-free survival among women with breast cancer. As the age of onset of menarche continues to decline, understanding its relationship to breast tumor characteristics and prognosis may lead to novel secondary prevention strategies.

Metabolomics of IgE-Mediated Food Allergy and Oral Immunotherapy Outcomes based on Metabolomic Profiling.

The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown. To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT. Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes. Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q=2.4×10 -20 ) and linoleic acid derivatives (q=3.8×10 -5 ) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q=4.1×10 -8 ), eicosanoids (q=7.9×10 -7 ), and histidine pathways (q=0.015). In particular, the bile acid lithocholate (4.97[1.93,16.14], p=0.0027), the eicosanoid leukotriene B4 (3.21[1.38,8.38], p=0.01), and the histidine metabolite urocanic acid (22.13[3.98,194.67], p=0.0015) were higher in SU. We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T-cell subsets, suggesting potential mechanisms of tolerance in immunotherapy. - Compared with unaffected controls, children with food allergy demonstrated higher levels of bile acids and distinct histidine/urocanic acid profiles, suggesting a potential role of these metabolites in food allergy. - In participants receiving oral immunotherapy for food allergy, those who were able to maintain tolerance-even after stopping therapyhad lower overall levels of bile acid and histidine metabolites, with the exception of lithocholic acid and urocanic acid, two metabolites that have roles in T cell differentiation that may increase the likelihood of remission in immunotherapy. This is the first study of plasma metabolomic profiles of responses to OIT in individuals with IgE-mediated food allergy. Identification of immunomodulatory metabolites in allergic tolerance may help identify mechanisms of tolerance and guide future therapeutic development.

Nonlinear dynamics of femtosecond laser interaction with the central nervous system in zebrafish

Understanding the photodamage mechanism underlying the highly nonlinear dynamic of femtosecond laser pulses at the second transparent window of tissue is crucial for label-free microscopy. Here, we report the identification of two cavitation regimes from 1030 nm pulses when interacting with the central nervous system in zebrafish. We show that at low repetition rates, the damage is confined due to plasma-based ablation and sudden local temperature rise. At high repetition rates, the damage becomes collateral due to plasma-mediated photochemistry. Furthermore, we investigate the role of fluorescence labels with linear and nonlinear absorption pathways in optical breakdown. To verify our findings, we examined cell death and cellular responses to tissue damage, including the recruitment of fibroblasts and immune cells after irradiation. These findings contribute to advancing the emerging nonlinear optical microscopy techniques and provide a strategy for inducing precise, and localized injuries using near-infrared femtosecond laser pulses.

A comparative assessment of policy induced diffusion pathways for utility scale solar PV: case study of Indonesia

Lack of effective policies hinder the uptake of Utility-scale solar PV, even though they are projected to play a pivotal role in achieving Indonesia's 2050 net-zero energy target. This study seeks to identify a cost-effective pathway to increase the capacity of utility-scale solar PV in Indonesia through supportive policies that ensure equitable cost distribution between the government and industry. A novel Market Penetration Optimization Model is developed and applied in simulation mode to assess existing policies, and optimization mode to determine new policy recommendations and compare three policy induced diffusion pathways. Results show that current price-based policies are insufficient to stimulate growth in the solar PV market, only covering ~13% of the investment cost required by the industry. Thus, necessitating a reactivation of Feed-in-Tariffs. The optimal tariffs rates required range from 0.39 to 1.47 cents/kWh for the most economic pathway during the initial 10-year post-construction period. The Innovation Diffusion Theory-based pathway necessitates the lowest initial investment cost while yielding the highest revenue from electricity sales, demonstrating its superior cost-effectiveness compared to both the supply-based and linear pathways. This study enriches the literature by exploring the financial implications of policy induced diffusion pathways.

Divergence of Classical and C-Ring-Cleaved Angucyclines: Elucidation of Early Tailoring Steps in Lugdunomycin and Thioangucycline Biosynthesis.

Angucyclines are an important group of microbial natural products that display tremendous chemical diversity. Classical angucyclines are composed of a tetracyclic benz[a]anthracene scaffold with one ring attached at an angular orientation. However, in atypical angucyclines, the polyaromatic aglycone is cleaved at A-, B-, or C-rings, leading to structural rearrangements and enabling further chemical variety. Here, we have elucidated the branching points in angucycline biosynthesis leading toward cleavage of the C-ring in lugdunomycin and thioangucycline biosynthesis. We showed that 12-hydroxylation and 6-ketoreduction of UWM6 are shared steps in classical and C-ring-cleaved angucycline pathways, although the bifunctional 6-ketoreductase LugOIIred harbors additional unique 1-ketoreductase activity. We identified formation of the key intermediate 8-O-methyltetrangomycin by the LugN methyltransferase as the branching point toward C-ring-cleaved angucyclines. The final common step in lugdunomycin and thioangucycline biosynthesis is quinone reduction, catalyzed by the 7-ketoreductases LugG and TacO, respectively. In turn, the committing step toward thioangucyclines is 12-ketoreduction catalyzed by TacA, for which no orthologous protein exists on the lugdunomycin pathway. Our results confirm that quinone reductions are early tailoring steps and, therefore, may be mechanistically important for subsequent C-ring cleavage. Finally, many of the tailoring enzymes harbored broad substrate promiscuity, which we utilized in combinatorial enzymatic syntheses to generate the angucyclines SM 196 A and hydranthomycin. We propose that enzyme promiscuity and the competition of many of the enzymes for the same substrates lead to a branching biosynthetic network and formation of numerous shunt products typical for angucyclines rather than a canonical linear metabolic pathway.

Chemotactic Interactions Drive Migration of Membraneless Active Droplets.

In nature, chemotactic interactions are ubiquitous and play a critical role in driving the collective behavior of living organisms. Reproducing these interactions in vitro is still a paramount challenge due to the complexity of mimicking and controlling cellular features, such as tangled metabolic networks, cytosolic macromolecular crowding, and cellular migration, on a microorganism size scale. Here, we generate enzymatically active cell-sized droplets able to move freely, and by following a chemical gradient, able to interact with the surrounding droplets in a collective manner. The enzyme within the droplets generates a pH gradient that extends outside the edge of the droplets. We discovered that the external pH gradient triggers droplet migration and controls its directionality, which is selectively toward the neighboring droplets. Hence, by changing the enzyme activity inside the droplet, we tuned the droplet migration speed. Furthermore, we showed that these cellular-like features can facilitate the reconstitution of a simple and linear protometabolic pathway and increase the final reaction product generation. Our work suggests that simple and stable membraneless droplets can reproduce complex biological phenomena, opening new perspectives as bioinspired materials and synthetic biology tools.

Spatio-Temporal Study of Galactolipid Biosynthesis in Duckweed Using Mass Spectrometry Imaging and in vivo Isotope Labeling.

Isotope labeling coupled with mass spectrometry imaging (MSI) presents a potent strategy for elucidating the dynamics of metabolism at cellular resolution, yet its application to plant systems is scarce. It has the potential to reveal the spatio-temporal dynamics of lipid biosynthesis during plant development. In this study, we explore its application to galactolipid biosynthesis of an aquatic plant, Lemna minor, with D2O labeling. Specifically, matrix-assisted laser desorption/ionization-MSI data of two major galactolipids in L. minor, monogalactosyldiacylglycerol and digalactosyldiacylglycerol, were studied after growing in 50% D2O media over a 15-day time period. When they were partially labeled after 5 d, three distinct binomial isotopologue distributions were observed corresponding to the labeling of partial structural moieties: galactose only, galactose and a fatty acyl chain and the entire molecule. The temporal change in the relative abundance of these distributions follows the expected linear pathway of galactolipid biosynthesis. Notably, their mass spectrometry images revealed the localization of each isotopologue group to the old parent frond, the intermediate tissues and the newly grown daughter fronds. Besides, two additional labeling experiments, (i) 13CO2 labeling and (ii) backward labeling of completely 50% D2O-labeled L. minor in H2O media, confirm the observations in forward labeling. Furthermore, these experiments unveiled hidden isotopologue distributions indicative of membrane lipid restructuring. This study suggests the potential of isotope labeling using MSI to provide spatio-temporal details in lipid biosynthesis in plant development.

Supporting the Wellbeing of Children with Special Needs through Strength Based Curriculum

Singapore’s Ministry of Social and Family Development’s definition of “persons with disability” are those with physical and mental impairments, therefore resulting in reduced opportunities towards a higher quality of life in terms of education, employment, and recreation (MSF, 2023). This identification of a disability is rooted on the affliction rather than the person. Mental health approaches have traditionally followed a linear deficit approach pathway as well, with the prescription that the termination of problems would in default result in a healthy state of mental health (Torres, 2021) and past policies and efforts were made to mitigate the affliction, in the view that the quality of life will improve in the absence of mental illness or the reduction of disability. Therefore, such endeavours on rehabilitation thrusts need to be revisited and revised, to accommodate the broader context children with special needs are part of. The present literature review seeks to explore the relationship of strength-based approaches on three variables, namely, self-esteem, self-concept and self-perception and its effect on overall well-being. These two variables were selected for two reasons. The first being their centrality to theories of positive psychology and have been long explored as indictors of wellbeing and scholastic levels (Baumeister, 2003). Second, these variables seem to have good predictable validity of self-views (Swann et al., 2007).

Enhancing 360° virtual laboratory safety training with linear learning pathway design: Insights from student experiences

This paper investigates the role of learning pathway design in a web-based 360° virtual laboratory safety training. A linearly structured virtual laboratory safety training was designed and implemented. Student experiences with the linear learning pathway were compared with a previously implemented non-linear learning pathway. In the linear pathway, students complete the virtual laboratory tour in a predetermined order, while in a non-linear pathway the students can complete the virtual laboratory tour in any order. Student feedback was collected from over 900 students and the experiences from the linearly structured virtual laboratory were highly positive. Compared to the previously implemented non-linear learning pathway, the student feedback related to the learning experience improved significantly. The feedback also showed a difference between preferred learning styles, highlighting the importance of choosing the learning pathway based on the intended learning outcomes and offering different types of learning materials for different learners. Overall, the findings of this study indicate that the linearly structured virtual laboratory offers an effective and motivating learning environment for laboratory safety training.

Stimuli-induced NOergic Molecules and Neuropeptides Mediated Axon Reflexes Contribute to Tracers along Meridian Pathways.

An abundance of studies from different international groups have demonstrated tracers along linear pathways resembling meridians over the body surface of humans. All experiments of the studies have been conducted by injection of a radiotracer solution or tracer dyes in a volume of solution into acupuncture points (acupoints). The solution injected into acupoints produces much stronger mechanical stimuli than acupuncture, which causes axon reflex. Anatomical studies have demonstrated that acupoints/meridians exist higher number of small nerve fibers and blood vessels with rich nitric oxide (NO) and neuropeptides in the cutaneous tissues as structures for the biomolecules mediated axon reflexes. Recent advances have determined that NO and calcitonin generelated peptides play crucial roles in the comprehension of the axon reflex. The stimuli-evoked axon reflex and NOergic biomolecules/neuropeptides increase local blood flow with higher levels in acupoints/meridians, which move radioactive substances or tracer dyes in the skin and subcutaneous tissue under a linear path resembling acupoints and meridians, the important phenomena of meridians induced by the stimuli. The evidence and understanding of the biomolecular processes of the tracers along linear pathways resembling meridians have been summarized with an emphasis on recent developments of NO and neuropeptides mediating stimuli-evoked axon reflexes to increase local blood flow with higher levels in acupoints/meridians, which move radioactive substances or tracer dyes in the skin and subcutaneous tissue contributing to tracers along linear pathways resembling meridians in this mini-review.

The Interaction and Effect of a Small MitoBlock Library as Inhibitor of ALR Protein-Protein Interaction Pathway.

MIA40 and ALR of the MIA pathway mediate the import of protein precursors that form disulfides into the mitochondrial intermembrane space. This import pathway is suggested to be a linear pathway in which MIA40 first binds to the precursor via a disulfide linkage and oxidizes it. Subsequently, ALR re-oxidizes MIA40 and then ALR transfers electrons to terminal electron acceptors. However, the precise mechanism by which ALR and MIA40 coordinate translocation is unknown. With a collection of small molecule modulators (MB-5 to MB-9 and MB-13) that inhibit ALR activity, we characterized the import mechanism in mitochondria. NMR studies show that most of the compounds bind to a similar region in ALR. Mechanistic studies with small molecules demonstrate that treatment with compound MB-6 locks the precursor in a state bound to MIA40, blocking re-oxidation of MIA40 by ALR. Thus, small molecules that target a similar region in ALR alter the dynamics of the MIA import pathway differently, resulting in a set of probes that are useful for studying the catalysis of the redox-regulated import pathway in model systems.

Activation of Ca2+ phosphatase Calcineurin regulates Parkin translocation to mitochondria and mitophagy in flies

Selective removal of dysfunctional mitochondria via autophagy is crucial for the maintenance of cellular homeostasis. This event is initiated by the translocation of the E3 ubiquitin ligase Parkin to damaged mitochondria, and it requires the Serine/Threonine-protein kinase PINK1. In a coordinated set of events, PINK1 operates upstream of Parkin in a linear pathway that leads to the phosphorylation of Parkin, Ubiquitin, and Parkin mitochondrial substrates, to promote ubiquitination of outer mitochondrial membrane proteins. Ubiquitin-decorated mitochondria are selectively recruiting autophagy receptors, which are required to terminate the organelle via autophagy. In this work, we show a previously uncharacterized molecular pathway that correlates the activation of the Ca2+-dependent phosphatase Calcineurin to Parkin translocation and Parkin-dependent mitophagy. Calcineurin downregulation or genetic inhibition prevents Parkin translocation to CCCP-treated mitochondria and impairs stress-induced mitophagy, whereas Calcineurin activation promotes Parkin mitochondrial recruitment and basal mitophagy. Calcineurin interacts with Parkin, and promotes Parkin translocation in the absence of PINK1, but requires PINK1 expression to execute mitophagy in MEF cells. Genetic activation of Calcineurin in vivo boosts basal mitophagy in neurons and corrects locomotor dysfunction and mitochondrial respiratory defects of a Drosophila model of impaired mitochondrial functions. Our study identifies Calcineurin as a novel key player in the regulation of Parkin translocation and mitophagy.

DAMPAK PEMBANGUNAN ABDUL RASYID TOWER TERHADAP PERUBAHAN ARUS LALU LINTAS DI KABUPATEN KOTAWARINGIN BARAT

In line with population growth, Pangkalan Bun City has now expanded to include linear pathways or the surrounding area, not only in the city center. This has resulted in the City of Pangkalan Bun having many large trading centers and one of them is the construction of the Abdul Rasyid Tower on Jalan Udan Said in front of the CBI Group head office, Pangkalan Bun, West Kotawaringin Regency, which will result in congestion / attraction of new trips in Pangkalan Bun City.&#x0D; Data collection was carried out by means of a direct survey at the Abdul Rasyid Tower intersection on Jalan Udan Said during peak hours in the morning, afternoon and evening from 06.00 – 18.00 WIB. From the survey results, grouping was carried out on each segment at the intersection and presented in the form of a vehicle table. In calculating the savings analysis using the 1997 Indonesian Highway Capacity Manual and Vissim Software. Traffic performance around the Abdul Rasyid Tower project site at the time prior to construction according to MKJI 1997 calculations, the biggest delay at the afternoon intersection at the first intersection was 7,45 second. The results of the Vissim Software the biggest intersection delay occurred in the morning at the first intersection, which was 7,98 second. Traffic performance around the Abdul Rasyid Tower project site during construction according to MKJI 1997 calculations, the largest intersection delay occurred in the afternoon at the first intersection of 9,47 second. The results of the Vissim Software, the biggest delay at the intersection occurred in the afternoon at the first intersection at 9,89 second. Traffic performance around the Abdul Rasyid Tower project site during post-construction according to MKJI 1997 calculations, the largest intersection delay during the day at the first intersection was 7,78 second. The results of the Vissim Software, the largest delay at the first intersection during the day is 8,21 second.

Progresses and challenges of engineering thermophilic acetogenic cell factories.

Thermophilic acetogens are gaining recognition as potent microbial cell factories, leveraging their unique metabolic capabilities to drive the development of sustainable biotechnological processes. These microorganisms, thriving at elevated temperatures, exhibit robust carbon fixation abilities via the linear Wood-Ljungdahl pathway to efficiently convert C1 substrates, including syngas (CO, CO2 and H2) from industrial waste gasses, into acetate and biomass via the central metabolite acetyl-CoA. This review summarizes recent advancements in metabolic engineering and synthetic biology efforts that have expanded the range of products derived from thermophilic acetogens after briefly discussing their autotrophic metabolic diversity. These discussions highlight their potential in the sustainable bioproduction of industrially relevant compounds. We further review the remaining challenges for implementing efficient and complex strain engineering strategies in thermophilic acetogens, significantly limiting their use in an industrial context.

Short Communication: Biogenic carbon in fast-moving products: A deception or real contribution to circularity?

Packaging is lately identified as one of the biggest environmental problems and is at a focus of the scientific community and the industry aiming at minimizing environmental impacts. One of the most applied eco-design measures is to substitute traditional packaging materials with bio-based materials. One of the driving incentives for the packaging industry is the calculation of biogenic carbon (BC), even though there is no unified method for the calculation of credits from carbon sequestration.We developed a case study of paper-based packaging and tested the two variables important in the circular economy: (i) material, by modeling three different end-of-life scenarios; (ii) and time, by assessing the importance of this variable using bottom-up and top-down calculations.The results of the case study showed that credits from carbon sequestration could lead to undesirable linear pathways of the EoL, by giving the biggest credits for landfilling and, thus, contradicting the circularity principles. Moreover, the time variable is critical for the calculation of biogenic carbon. Credits for carbon sequestration for short-lived products can lead to an overestimation of the storing impact because the top-down calculus of national inventories, developed based on the UNFCCC method, cannot register carbon savings.This short communication indicates that we need to invest in additional research to identify the correct way to calculate the carbon credits when using bio-based materials and to improve the practice for calculations of the overall carbon footprint of the short-lived materials in the technosphere.