Global analysis of aging-related protein structural changes uncovers enzyme-polymerization-based control of longevity.

Aging is associated with progressive phenotypic changes. Virtually all cellular phenotypes are produced by proteins, and their structural alterations can lead to age-related diseases. However, we still lack comprehensive knowledge of proteins undergoing structural-functional changes during cellular aging and their contributions to age-related phenotypes. Here, we conducted proteome-wide analysis of early age-related protein structural changes in budding yeast using limited proteolysis-mass spectrometry (LiP-MS). The results, compiled in online ProtAge catalog, unraveled age-related functional changes in regulators of translation, protein folding, and amino acid metabolism. Mechanistically, we found that folded glutamate synthase Glt1 polymerizes into supramolecular self-assemblies during aging, causing breakdown of cellular amino acid homeostasis. Inhibiting Glt1 polymerization by mutating the polymerization interface restored amino acid levels in aged cells, attenuated mitochondrial dysfunction, and led to lifespan extension. Altogether, this comprehensive map of protein structural changes enables identifying mechanisms of age-related phenotypes and offers opportunities for their reversal.

Overcoming Challenges: Extending Cycle Life of Aqueous Zinc-Ion Batteries at High Zinc Utilization through a Synergistic Strategy.

Aqueous zinc-ion batteries (AZIBs) face challenges in achieving high energy density compared to conventional lithium-ion batteries (LIBs). The lower operating voltage and excessive Zn metal as anode pose constraints on the overall energy storage capacity of these batteries. An effective approach is to reduce the thickness of the Zn metal anode and control its mass appropriately. However, under the condition of using a thin Zn anode, the performance of AZIBs is often unsatisfactory. Through experiments and computational simulations, the electrode structural change and the formation of dead Zn as the primary reasons for the failure of batteries under a high Zn utilization rate are identified. Based on this understanding, a universal synergistic strategy that combines Cu foil current collectors and electrolyte additives to maintain the structural and thermodynamic stability of the Zn anode under a high Zn utilization rate (ZUR) is proposed. Specifically, the Cu current collectors can ensure that the Zn anode structure remains intact based on the spontaneous filling effect, while the additives can suppress parasitic side reactions at the interface. Ultimately, the symmetric cell demonstrates a cycling duration of 900 h at a 70% ZU, confirming the effectiveness of this strategy.

Evaluating the employment effects of environmental regulation without abatement cost data: A nonparametric cost function approach.

Environmental policymakers are concerned that environmental regulations reduce employment. A microeconomic analysis illustrates that environmental regulations have an uncertain effect on employment, making this an empirical question. A standard cost function model, used in the literature, requires a lot of data such as pollution abatement cost data to examine effects of environmental regulations on employment, but such survey data is not always available. In this paper, we develop a nonparametric cost function which alleviates the need for pollution abatement cost data. Our cost function, therefore, allows researchers and policy analysts to estimate employment changes associated with pollution abatement as well as measure the relative importance of other factors related to changes in employment with no pollution abatement cost data. Moreover, this is the first model using a cost function that incorporates the effect of structural change among industries within the economy on employment, which allows researchers to the examine how environmental regulations change the structure of the economy via a structural decomposition component. We illustrate how to operationalize our model using a balanced panel of industry-level data for 26 industries from 17 OECD countries (1995-2006). Our findings suggest that the change in employment due to regulatory induced increases in input costs exhibits both substantial variation among countries and substantial intra-country heterogeneity among industries.

Evaluating forest depletion and structural change effects on environmental sustainability in Pakistan: Through the lens of the load capacity factor.

The pace of species extinction and deforestation has increased dramatically due to the substantial increase in global environmental degradation. This trend is approaching the crucial temperature threshold of 2 °C and calls for more attention. Although previous research has observed the individual impacts of forest depletion, structural change, economic growth, and urbanization on various sustainability outcomes, there has been no previous research into their interrelationships with an emphasis on the load capacity factor (LCF). Furthermore, no previous study has examined the environmental impacts of the abovementioned variables by contrasting the results of LCF and CO2 emissions in Pakistan. Therefore, this research suggests a theoretical framework that integrates these concepts, provides a roadmap for an effective and sustainable mitigation strategy for Pakistan and compares LCF results with CO2 emissions. Using the time-series data from 1970 to 2021, a unique and sophisticated dynamic Autoregressive Distributed Lag (DARDL) technique, the authors found that (i) a 1 % rise in forest depletion leads to a decline in load capacity factor by 0.026 %. (ii) A one per cent upsurge in structural change fosters environmental sustainability by raising the load capacity factor by 0.084 %. (iii) An increase of 1 % in economic growth dwindles the load capacity factor by 0.027 %. (iv) A one per cent surge in urbanization enhances the load capacity factor by 0.029 %. The findings suggest that Pakistan's Government should promote afforestation by emphasizing the constructive role of structural change in achieving environmental sustainability.

Going green while getting lean: Decomposing carbon and green total factor productivity.

While research on carbon productivity is growing rapidly, the role of structural change in green transition remains unexplored due to the scarcity of firm-level emission data. This study addresses this gap by utilizing unique register-based greenhouse gas emission data from Finland's energy-intensive manufacturing firms for 2000-2019. Applying a structural change productivity decomposition, we break down the sector's carbon productivity and green total factor productivity into four components: contributions from non-switching continuing firms, industry-switching continuing firms, the effects of entry and exit, and resource allocation. The findings highlight the important role of structural change in the sector's productivity. Non-switching continuing firms emerged as the key drivers of both carbon and green total factor productivity growth. The contribution of entry and exit was negative during the financial crisis, while inefficient resource allocation significantly hindered productivity growth throughout the study period. These findings emphasize the importance of public subsidies targeted at environmentally efficient firms to enhance their competitiveness under challenging market conditions. Furthermore, the establishment of a stable yet positive carbon price would incentivize less-productive firms to adopt environmentally friendly technologies.

Association between intestinal microflora and renal function in patients with chronic renal failure: A case-control analysis.

Objective: To identify the association between the changes in intestinal microflora and renal function in patients with chronic renal failure (CRF). Methods: This retrospective case-control study included 50 patients with CRF (study group), admitted to the Clinical Laboratory Department of Shenzhen People's Hospital from March 2021 to May 2022, and 50 healthy individuals (control group). The association between the distribution of intestinal microflora and the glomerular filtration rate (GFR), levels of serum creatinine (SCr), blood urea nitrogen (BUN), and serum cystatin C (CysC) were analyzed. Results: Intestinal microflora of CRF patients had significantly higher levels of Enterococci compared to the control group (p-Value <0.05), while the levels of Bifidobacterium spp. and Escherichia coli were lower in the study group (p-Value <0.05). GFR was lower, and the levels of BUN, SCr, and CysC were higher in the study group compared to the control group (all p-Value <0.05). GFR, BUN, SCr and CysC levels in the study group negatively correlated with the levels of Bifidobacterium spp. and Lactobacillus spp. (r<0, P<0.05), and positively correlated with the abundance of Enterococcus spp. and Escherichia coli (r>0, P<0.05) in the intestinal microflora. Conclusions: Changes in intestinal microbiota are associated with a significant decrease in GFR and a marked increase in serum levels of renal function indicators, and alterations in the balance of intestinal microbiota may lead to further aggravation of the renal function damage in patients with CRF.

Cooperation and competition by RNA-binding proteins in cancer.

Post-transcriptional regulation of gene expression plays a major role in determining the cellular proteome in health and disease. Post-transcriptional control mechanisms are disrupted in many cancers, contributing to multiple processes of tumorigenesis. RNA-binding proteins (RBPs), the main post-transcriptional regulators, often show altered expression and activity in cancer cells. Dysregulation of RBPs contributes to many cancer phenotypes, functioning in complex regulatory networks with other cellular players such as non-coding RNAs, signaling mediators and transcription factors to alter the expression of oncogenes and tumor suppressor genes. RBPs often function combinatorially, based on their binding to target sequences/structures on shared mRNA targets, to regulate the expression of cancer-related genes. This gives rise to cooperativity and competition between RBPs in mRNA binding and resultant functional outcomes in post-transcriptional processes such as mRNA splicing, stability, export and translation. Cooperation and competition is also observed in the case of interaction of RBPs and microRNAs with mRNA targets. RNA structural change is a common mechanism mediating the cooperative/competitive interplay between RBPs and between RBPs and microRNAs. RNA modifications, leading to changes in RNA structure, add a new dimension to cooperative/competitive binding of RBPs to mRNAs, further expanding the RBP regulatory landscape. Therefore, cooperative/competitive interplay between RBPs is a major determinant of the RBP interactome and post-transcriptional regulation of gene expression in cancer cells.

Temporal change in functional rarity in marine fish assemblages.

Recent research has uncovered rapid compositional and structural reorganization of ecological assemblages, with these changes particularly evident in marine ecosystems. However, the extent to which these ongoing changes in taxonomic diversity are a proxy for change in functional diversity is not well understood. Here we focus on trends in rarity to ask how taxonomic rarity and functional rarity covary over time. Our analysis, drawing on 30 years of scientific trawl data, reveals that the direction of temporal shifts in taxonomic rarity in two Scottish marine ecosystems is consistent with a null model of change in assemblage size (i.e. change in numbers of species and/or individuals). In both cases, however, functional rarity increases, as assemblages become larger, rather than showing the expected decrease. These results underline the importance of measuring both taxonomic and functional dimensions of diversity when assessing and interpreting biodiversity change.

Information criteria for detecting change-points in the Cox proportional hazards model.

The Cox proportional hazards model, commonly used in clinical trials, assumes proportional hazards. However, it does not hold when, for example, there is a delayed onset of the treatment effect. In such a situation, an acute change in the hazard ratio function is expected to exist. This paper considers the Cox model with change-points and derives Akaike information criterion (AIC)-type information criteria for detecting those change-points. The change-point model does not allow for conventional statistical asymptotics due to its irregularity, thus a formal AIC that penalizes twice the number of parameters would not be analytically derived, and using it would clearly give overfitting analysis results. Therefore, we will construct specific asymptotics using the partial likelihood estimation method in the Cox model with change-points, and propose information criteria based on the original derivation method for AIC. If the partial likelihood is used in the estimation, information criteria with penalties much larger than twice the number of parameters could be obtained in an explicit form. Numerical experiments confirm that the proposed criteria are clearly superior in terms of the original purpose of AIC, which are to provide an estimate that is close to the true structure. We also apply the proposed criterion to actual clinical trial data to indicate that it will easily lead to different results from the formal AIC.

Detection of novel variant and functional study in a Chinese family with nonsyndromic oligodontia.

OBJECTIVES: To investigate the pathogenic gene of a patient with nonsyndromic oligodontia, and analyze its possible pathogenic mechanism. SUBJECTS AND METHODS: The variant was detected by whole exome sequencing (WES) and Sanger sequencing in a family with oligodontia. Bioinformatic and structural analyses were used to analyze variant. Functional studies including western blotting and immunofluorescent analyses and luciferase reporter assay were conducted to explore the functional effects. RESULTS: We identified a novel frameshift variant of PAX9 (c.491-510delGCCCT-ATCACGGCGGCGGCC, p.P165Qfs*145) outside the DNA-binding domain causing an autosomal-dominant nonsyndromic oligodontia in a Chinese family. Bioinformatic and structural analyses revealed that the variant is pathogenic and conserved evolutionarily, and the changes might affect protein stability or folding. Functional studies demonstrate dramatically reduced ability in activating transcription activity of BMP4 promoter and a marked decrease in protein production, as evaluated by western blotting and immunofluorescent analyses. CONCLUSIONS: We found a novel frameshift variant of PAX9 causing nonsyndromic oligodontia in a Chinese family. Our findings indicate that frameshift variants cause loss of function of PAX9 protein during the patterning of the dentition and the subsequent tooth agenesis, providing new molecular insights into the role of frameshift variant of PAX9 and broaden the pathogenic spectrum of PAX9 variants.

Highly sensitive tryptophan fluorescence probe for detecting rhythmic conformational changes of KaiC in the cyanobacterial circadian clock system.

KaiC, a core protein of the cyanobacterial circadian clock, consists of an N-terminal CI domain and a C-terminal CII domain, and assembles into a double-ring hexamer upon binding with ATP. KaiC rhythmically phosphorylates and dephosphorylates its own two adjacent residues Ser431 and Thr432 at the CII domain with a period of ∼24 h through assembly and disassembly with the other clock proteins, KaiA and/or KaiB. In this study, to understand how KaiC alters its conformation as the source of circadian rhythm, we investigated structural changes of an inner-radius side of the CII ring using time-resolved Trp fluorescence spectroscopy. A KaiC mutant harboring a Trp fluorescence probe at a position of 419 exhibited a robust circadian rhythm with little temperature sensitivity in the presence of KaiA and KaiB. Our fluorescence observations show a remarkable environmental change at the inner-radius side of the CII ring during circadian oscillation. Crystallographic analysis revealed that a side chain of Trp at the position of 419 was oriented toward a region undergoing a helix-coil transition, which is considered to be a key event to allosterically regulate the CI ring that plays a crucial role in determining the cycle period. The present study provides a dynamical insight into how KaiC generates circadian oscillation.

Should I stay or should I go? The impact of nature reserves on the survival and growth of dairy farms.

Special Areas of Conservation (SAC) are part of the EU's nature protection network Natura 2000. SAC often protect nitrogen-sensitive flora and fauna. This is challenging for livestock farmers because they have to meet strict requirements for emission reduction and need to implement costly environmental protection measures. Therefore, SAC could limit farmers' chances to grow or even to survive. This article aims to determine the effects of SAC on dairy farmers by using a Heckman sample selection model. The model explores i) the factors that are relevant to the decision to maintain the farm's existing structure, increase dairy production, exit dairy, or exit agriculture altogether, ii) an OLS regression to analyse the factors that determine the amount of growth in dairy numbers. The analysis was performed for two periods and is based on annual financial statements and regional data such as information about SAC locations. In the first step, the results confirmed the initial hypothesis, finding that farms in districts with more land under nature conservation had a smaller probability of growth. For one of the two periods analysed, higher probabilities of exiting dairy were observed. The second part of the analysis showed that the amount of growth was not affected by SAC protection. The results indicate that SAC protection is indeed challenging for dairy farmers. Further research on the topic is necessary as the area under protection will increase. Since the protected species also depend on (extensive) farming practices, it might be necessary to provide development prospects to farmers that better align with biodiversity objectives.

Recovery from chronic depression and structural change: 5-year outcomes after psychoanalytic and cognitive-behavioural long-term treatments (LAC depression study).

OBJECTIVE: Psychotherapy of chronic depression has remained a challenge due to limited prognosis and high rates of recurrence. We present 5-year outcome data from a multicentre trial comparing psychoanalytic (PAT) and cognitive-behavioural (CBT) long-term treatments with randomized and preferred allocations analysing symptom (N = 227) and structural change (N = 134) trajectories. METHOD: Self- and blinded expert ratings of depression symptoms were performed at yearly intervals using the Beck Depression Inventory-II (BDI-II) and Quick Inventory of Depressive Symptoms (QIDS-C). Blinded expert ratings of Operationalized Psychodynamic Diagnosis (OPD) and the Heidelberg Restructuring Scale (HRS) at baseline, 1, 3, and 5 years assessed structural change in a subsample. RESULTS: Lasting and comparable symptom changes were achieved by PAT and CBT. However, compared to CBT, PAT was more successful in restructuring, a major goal of long-term psychodynamic treatments with high frequency and duration. LIMITATIONS: Due to practical reasons, the time criterion for chronic depression of an acute phase had to be defined for over 1 year in the present study, which does not correspond to the DSM-5 criterion of 2 years. Therapy duration and session frequency were not incorporated into the statistical models. CONCLUSION: Long-term psychotherapy helps patients with a yearlong history of depression and often multiple unsuccessful treatment attempts to achieve lasting symptom changes. Future follow-up will clarify whether restructuring promotes further sustainable improvements.

Asymmetric effect of structural change and renewable energy consumption on carbon emissions: designing an SDG framework for Turkey.

A plethora of studies have shown that structural change helps nations achieve socioeconomic growth. The influence of structural change on environmental quality, on the other hand, has yet to be thoroughly investigated. As a result, the current study assesses the asymmetric impact of structural change on CO2 emissions while controlling for the effects of economic progress, renewable energy utilization, and nonrenewable energy in Turkey. To this end, this research used yearly data stretching from 1965 to 2019. The study applied several econometric approaches including nonlinear auto-regressive distributed lag (NARDL) and spectral causality to assess these associations. The outcomes from the NARDL reveal that variations in the regressors have a nonlinear influence on CO2 in Turkey. Moreover, the transition in the economy's structure helps to boost ecological quality, while the findings also show that Turkey's current economic progress trajectory is unsustainable due to the country's reliance on fossil fuel-based energy consumption. The outcomes of the spectral causality test also show that structural change can predict CO2 emissions in Turkey at different frequencies. Based on the study findings, the government should encourage investment in the service sector in order to maintain a suitable level of environmental sustainability.

Inhibitory mechanisms of polyphenols on heme protein-mediated lipid oxidation in muscle food: New insights and advances.

Lipid oxidation is a major cause of quality deterioration that decreases the shelf-life of muscle-based foods (red meat, poultry, and fish), in which heme proteins, particularly hemoglobin and myoglobin, are the primary pro-oxidants. Due to increasing consumer concerns over synthetic chemicals, extensive research has been carried out on natural antioxidants, especially plant polyphenols. The conventional opinion suggests that polyphenols inhibit lipid oxidation of muscle foods primarily owing to their strong hydrogen-donating and transition metal-chelating activities. Recent developments in analytical techniques (e.g., protein crystallography, nuclear magnetic resonance spectroscopy, fluorescence anisotropy, and molecular docking simulation) allow deeper understanding of the molecular interaction of polyphenols with heme proteins, phospholipid membrane, reactive oxygen species, and reactive carbonyl species; hence, novel hypotheses regarding their antioxidant mechanisms have been formulated. In this review, we summarize five direct and three indirect pathways by which polyphenols inhibit heme protein-mediated lipid oxidation in muscle foods. We also discuss the relation between chemical structures and functions of polyphenols as antioxidants.

Moiré Superlattice-Induced Superconductivity in One-Unit-Cell FeTe.

In this work, we demonstrate that the nonsuperconducting single-layer FeTe can become superconducting when its structure is properly tuned by epitaxially growing it on Bi2Te3 thin films. The properties of the single-layer FeTe deviate strongly from its bulk counterpart, as evidenced by the emergence of a large superconductivity gap (3.3 meV) and an apparent 8 × 2 superlattice (SL). Our first-principles calculations indicate that the 8 × 2 SL and the emergence of the novel superconducting phase are essentially the result of the structural change in FeTe due to the presence of the underlying Bi2Te3 layer. The structural change in FeTe likely suppresses the antiferromagnetic order in the FeTe and leads to superconductivity. Our work clearly demonstrates that moiré pattern engineering in a heterostructure is a reachable dimension for investigating novel materials and material properties.

CpG Methylation Altered the Stability and Structure of the i-Motifs Located in the CpG Islands.

Cytosine methylation within the 5'-C-phosphate-G-3' sequence of nucleotides (called CpG methylation) is a well-known epigenetic modification of genomic DNA that plays an important role in gene expression and development. CpG methylation is likely to be altered in the CpG islands. CpG islands are rich in cytosine, forming a structure called the i-motif via cytosine-cytosine hydrogen bonding. However, little is known about the effect of CpG methylation on the i-motif. In this study, The CpG methylation-induced structural changes on the i-motif was examined by thermal stability, circular dichroism (CD) spectroscopy, and native-polyacrylamide gel electrophoresis (Native-PAGE) evaluation of five i-motif-forming DNAs from four cancer-related genes (VEGF, C-KIT, BCL2, and HRAS). This research shows that CpG methylation increased the transitional pH of several i-motif-forming DNAs and their thermal stability. When examining the effect of CpG methylation on the i-motif in the presence of opposite G4-forming DNAs, CpG methylation influenced the proportion of G4 and i-motif formation. This study showed that CpG methylation altered the stability and structure of the i-motif in CpG islands.

Post-script-Retail forecasting: Research and practice.

This note updates the 2019 review article "Retail forecasting: Research and practice" in the context of the COVID-19 pandemic and the substantial new research on machine-learning algorithms, when applied to retail. It offers new conclusions and challenges for both research and practice in retail demand forecasting.

History and Perspectives of Ion-Transporting Rhodopsins.

The first light-sensing proteins used in optogenetics were rhodopsins. The word "rhodopsin" originates from the Greek words "rhodo" and "opsis," indicating rose and sight, respectively. Although the classical meaning of rhodopsin is the red-colored pigment in our eyes, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins possess 11-cis and all-trans retinal, respectively, to capture light in seven transmembrane α-helices, and photoisomerizations into all-trans and 13-cis forms, respectively, initiate each function. We are able to find ion-transporting proteins in microbial rhodopsins, such as light-gated channels and light-driven pumps, which are the main tools in optogenetics. In this chapter, historical aspects and molecular properties of rhodopsins are introduced. In the first part, "what is rhodopsin?", general introduction of rhodopsin is presented. Then, molecular mechanism of bacteriorodopsin, a light-driven proton pump and the best-studied microbial rhodopsin, is described. In the section of channelrhodopsin, the light-gated ion channel, molecular properties, and several variants are introduced. As the history has proven, understanding the molecular mechanism of microbial rhodopsins is a prerequisite for useful functional design of optogenetics tools in future.

The effects of long-term fertilizations on soil hydraulic properties vary with scales.

Soil structure is an indicator of soil quality and its alterations following cropping system conversion or fertilization change evolve slowly. How such alterations vary with scale remains elusive. We investigated this based on the Rothamsted long-term wheat experiment (since 1843) in the UK. Triplicate cores 7 cm high and 10 cm in diameter were taken from plots that have been under different fertilizations or returned to natural woodland for more than one century for imaging using X-ray computed tomography with the voxel size being 40 µm. We then broke each core and sampled three aggregates from it to scan with the voxel size being 1.5 µm. For each core and aggregate sample, we calculated its pore size distribution, permeability and tortuosity. The results showed that the fertilization change >170 years ago reshaped the soil structure differently between the core scale and the aggregate scale. Macro-porosity of the pores (>40 µm) in the cores unfertilized or fertilized with inorganic fertilizers was low and the pores were poorly connected in the top 10 cm of soil, compared to those given farmyard manure or in the woodland. In all treatments, the pores in the core images were hydraulically anisotropic with their permeability in the horizontal direction being higher than that in the vertical direction, whereas the aggregates were comparatively isotropic. The fertilization affected image porosity and permeability at core scale more significantly than at aggregate scale, and the aggregates fertilized with farmyard manure and in the woodland were more permeable than the aggregates in other treatments. It was also found that compared to no-fertilization or fertilization with complete fertilizers, fertilizing without phosphorus over the past 20 years increased the porosity and permeability of the aggregates but not of the cores. Fertilization with inorganic fertilizers increased the tortuosity of the macropores in the cores but not of the intra-aggregate pores, compared to no-fertilization. Porosity-permeability relationship for aggregates unfertilized or fertilized with inorganic fertilisers followed a power law with R 2 > 0.8. In contrast, the permeability of the aggregates in farmyard manure and in the woodland trended differently as their porosity increased. The results also revealed that the transport ability of the aggregates and cores responded differently to carbon in that with soil carbon increasing, the permeability of the aggregates increased asymptotically while the permeability of the cores, especially its horizontal component, increased exponentially.