Linear Linkage Research Articles

Investigating the Core Structure of Reuteran with High-Content Linear (α1 → 6) Linkages Synthesized by Limosilactobacillus mucosae L24-B GtfB-Type Glucanotransferase.

Reuteran is a functional homopolysaccharide comprising major (α1 → 4) and interspersed (α1 → 6) linkages whose properties and functions are directly associated with the structure. In order to enrich the structural variety and application prospects of reuteran, a GtfB-type 4,6-α-glucanotransferase from Limosilactobacillus mucosae L24-B (LmGtfB), which can synthesize reuteran with high-content linear (α1 → 6) linkages, was screened. LmGtfB exhibited 4,6-α-glucanotransferase activity against starch or dextrin and can synthesize both linear and branching (α1 → 6) linkages, which offered advantages in terms of source and cost. The as-produced reuteran had the highest content of linear (α1 → 6) linkages (19% in the methylation result) among the reuterans synthesized by other GtfB-type 4,6-α-glucanotransferases. A purification method was established and applied to the extraction of the core structure of the LmGtfB products. 1H NMR and enzymatic hydrolysis revealed that the core structure contains 46.24% (α1 → 6) linkages and alternating (α1 → 4)/(α1 → 6) linkages, which was formed by enzymatic transfer of maltose.

Properties, Synthesis and Emerging Applications of Graphdiyne: A Journey Through Recent Advancements.

Graphdiyne (GDY) is a new variant of nano-carbon material with excellent chemical, physical and electronic properties. It has attracted wide attention from researchers and industrialists for its extensive role in the fields of optics, electronics, bio-medics and energy. The unique arrangement of sp-sp2 carbon atoms, linear acetylenic linkages, uniform pores and highly conjugated structure offer numerous potentials for further exploration of GDY materials. However, since the material is at its infancy, not much understanding is available regarding its properties, growth mechanism and future applications. Therefore, in this review, readers are guided through a brief discussion on GDY's properties, different synthesis procedures with a special focus on surface functionalization and a list of applications for GDY. The review also critically analyses the advantages and disadvantages of each synthesis route and emphasizes the future scope of the material.

Dominant negative OTULIN-related autoinflammatory syndrome.

OTU deubiquitinase with linear linkage specificity (OTULIN) regulates inflammation and cell death by deubiquitinating linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC). Biallelic loss-of-function mutations causes OTULIN-related autoinflammatory syndrome (ORAS), while OTULIN haploinsuffiency has not been associated with spontaneous inflammation. However, herein, we identify two patients with the heterozygous mutation p.Cys129Ser in OTULIN. Consistent with ORAS, we observed accumulation of linear ubiquitin chains, increased sensitivity to TNF-induced death, and dysregulation of inflammatory signaling in patient cells. While the C129S mutation did not affect OTULIN protein stability or binding capacity to LUBAC and linear ubiquitin chains, it did ablate OTULIN deubiquitinase activity. Loss of activity facilitated the accumulation of autoubiquitin chains on LUBAC. Altered ubiquitination of LUBAC inhibits its recruitment to the TNF receptor signaling complex, promoting TNF-induced cell death and disease pathology. By reporting the first dominant negative mutation driving ORAS, this study expands our clinical understanding of OTULIN-associated pathology.

Downregulation of otulin induces inflammasome activation in neutrophilic asthma

Neutrophilic asthma (NA) is a severe asthma phenotype associated with steroid resistance and IL-1β overproduction; however, the exact mechanism remains unclear. Moreover, the dysfunction of TNF-α signaling pathway, a regulator of IL-1β production, was associated with the deficiency of ovarian tumor protease deubiquitinase with linear linkage specificity (otulin) in autoimmune patients. We hypothesized that otulin downregulation in macrophages (Mφ) could trigger Mφ activation via the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway. We assessed the expressions of otulin in blood monocyte subsets from NA patients and in alveolar Mφ from NA mice. Additionally, we evaluated the functional consequences of otulin deficiency in bone marrow-derived Mφ. The effects of inhibiting receptor-interacting protein kinase (RIPK)-1 and RIPK-3 on neutrophils and group 3 innate lymphoid cells (ILC3s) were assessed invitro and invivo. When comparing nonclassical monocytes, a significant downregulation of otulin in the intracellular components was observed in NA patients compared to healthy controls (P= .005). Moreover, isolated alveolar Mφ from the NA mice exhibited lower otulin expression compared to those from control mice. After otulin knockdown in bone marrow-derived Mφ, we observed spontaneous IL-1β production depending on NLRP3 inflammasome. Moreover, the infiltrated neutrophils and ILC3s were significantly decreased by combined treatment of RIPK-1 and RIPK-3 inhibitors through blocking IL-1β release in NA. IL-1β overproduction caused by a deficiency of otulin, an upstream triggering factor, could be a promising diagnostic and therapeutic target for NA.

Identification of a novel starch-converting GtfB enzyme from the Fructilactobacillus sanfranciscensis TMW11304 to reduce the viscoelasticity and retrogradation of tapioca starch

Starch-converting α-glucanotransferases are efficient enzymatic toolkits for the biosynthesis of diverse α-glucans, which hold vast application potential in the food industry. In this work, we identified a novel GtfB protein from Fructilactobacillus sanfranciscensis TMW11304 (FsTMW11304 GtfB) in NCBI. Although this enzyme was highly conserved in motifs I-IV with those isomalto-maltopolysaccharides (IMMPs)-producing GtfB α-glucanotransferases, it possessed distinct deletions and mutations in two crucial loops shaping the active site. Hence, unlike those GtfB enzymes, FsTMW11304 GtfB not only exhibited excellent 4,6-α-glucanotransferase activity on amylose to generate atypically low-molecular-weight IMMPs with consecutive linear (α1 → 6) linkages up to 48 %, but also held good capability towards branched substrates. Besides, compared with the control, the treatment by FsTMW11304 GtfB reduced the storage/loss modulus of granular and gelatinized tapioca starches (TS) by 12.0 %/17.9 % and 91.4 %/82.9 %, respectively, indicating that the rigidity of the gel structure was attenuated to different degrees in the two reaction systems. Furthermore, the setback viscosity observed in the gelatinized TS modified by FsTMW11304 GtfB was only 5 % of that observed in the control group, suggesting the short-term anti-retrogradation property has been substantially improved. Thus, FsTMW11304 GtfB represents a meaningful addition to the α-glucanotransferases in GH70 family, which expands the repertoire of diverse α-glucans synthesized from starch and facilitates the understanding of the structure-function relationship of the GtfB α-glucanotransferases.

Exploring a GtfB-Type 4,6-α-Glucanotransferase to Synthesize the (α1 → 6) Linkages in Linear Chain and Branching Points from Amylose and Enhance the Functional Property of Granular Corn Starches.

Starch-converting α-glucanotransferases of glycoside hydrolase family 70 (GH70) are promising enzymatic tools for the production of diverse α-glucans with (potential) commercial applications in food and health and as biomaterials. In this study, a novel GtfB enzyme from Weissella confusa MBF8-1 was screened in the National Center for Biotechnology Information (NCBI) nonredundant protein database. The enzyme (named WcMBF8-1 GtfB) displayed high conservation in motifs I-IV with other GtfB enzymes but possessed unique variations in several substrate-binding residues. Structural characterizations of its α-glucan products revealed that WcMBF8-1 GtfB exhibited an atypical 4,6-α-glucanotransferase activity and was capable of catalyzing, by cleaving off (α1 → 4)-linkages in starch-like substrates and the synthesis of linear (α1 → 6) linkages and (α1 → 4,6) branching points. The product specificity enlarges the diversity of α-glucans and facilitates recognition of the determinants of the linkage specificity in GtfB enzymes. Furthermore, the contents of slowly digestible starch and resistant starch of granular corn starches, modified by WcMBF8-1 GtfB, increased by 6.7%, which suggested the potential value for the utilization of WcMBF8-1 GtfB to prepare "clean-label" starch ingredients with improved functional attributes.

Simultaneous substrate and ubiquitin modification recognition by bispecific antibodies enables detection of ubiquitinated RIP1 and RIP2.

Ubiquitination is a posttranslational modification that is crucial for the dynamic regulation of diverse signaling pathways. To enhance our understanding of ubiquitination-mediated signaling, we generated a new class of bispecific antibodies that combine recognition of ubiquitination substrates and specific polyubiquitin linkages. RIP1-K63 and RIP1-linear (Lin) linkage polyubiquitin bispecific antibodies detected linkage-specific ubiquitination of the proinflammatory kinase RIP1 in cells and in tissues and revealed RIP1 ubiquitination by immunofluorescence. Similarly, ubiquitination of the RIP1-related kinase RIP2 with K63 or linear linkages was specifically detected with the RIP2-K63 and RIP2-Lin bispecific antibodies, respectively. Furthermore, using the RIP2-K63 and RIP2-Lin bispecific antibodies, we found prominent K63-linked and linear RIP2 ubiquitination in samples from patients with ulcerative colitis and Crohn's disease. We also developed a bispecific antibody (K63-Lin) that simultaneously recognizes K63-linked and linear ubiquitination of components of various signaling pathways. Together, these bispecific antibodies represent a new class of reagents with the potential to be developed for the detection of inflammatory biomarkers.

Association between machine learning-assisted heavy metal exposures and diabetic kidney disease: a cross-sectional survey and Mendelian randomization analysis.

Heavy metals, ubiquitous in the environment, pose a global public health concern. The correlation between these and diabetic kidney disease (DKD) remains unclear. Our objective was to explore the correlation between heavy metal exposures and the incidence of DKD. We analyzed data from the NHANES (2005-2020), using machine learning, and cross-sectional survey. Our study also involved a bidirectional two-sample Mendelian randomization (MR) analysis. Machine learning reveals correlation coefficients of -0.5059 and - 0.6510 for urinary Ba and urinary Tl with DKD, respectively. Multifactorial logistic regression implicates urinary Ba, urinary Pb, blood Cd, and blood Pb as potential associates of DKD. When adjusted for all covariates, the odds ratios and 95% confidence intervals are 0.87 (0.78, 0.98) (p = 0.023), 0.70 (0.53, 0.92) (p = 0.012), 0.53 (0.34, 0.82) (p = 0.005), and 0.76 (0.64, 0.90) (p = 0.002) in order. Furthermore, multiplicative interactions between urinary Ba and urinary Sb, urinary Cd and urinary Co, urinary Cd and urinary Pb, and blood Cd and blood Hg might be present. Among the diabetic population, the OR of urinary Tl with DKD is a mere 0.10, with a 95%CI of (0.01, 0.74), urinary Co 0.73 (0.54, 0.98) in Model 3, and urinary Pb 0.72 (0.55, 0.95) in Model 2. Restricted Cubic Splines (RCS) indicate a linear linkage between blood Cd in the general population and urinary Co, urinary Pb, and urinary Tl with DKD among diabetics. An observable trend effect is present between urinary Pb and urinary Tl with DKD. MR analysis reveals odds ratios and 95% confidence intervals of 1.16 (1.03, 1.32) (p = 0.018) and 1.17 (1.00, 1.36) (p = 0.044) for blood Cd and blood Mn, respectively. In the general population, urinary Ba demonstrates a nonlinear inverse association with DKD, whereas in the diabetic population, urinary Tl displays a linear inverse relationship with DKD.

Revised structure of the polysaccharide from Acinetobacter baumannii LUH5551 assigned as the K63 type capsular polysaccharide

K63 capsular polysaccharide produced by Acinetobacter baumannii isolate LUH5551 (previously designated isolate O24) was re-examined using sugar analysis, Smith degradation, and one- and two-dimensional 1H and 13C NMR spectroscopy. Though previously reported as O24 consisting of linear tetrasaccharide units that include a 7-acetamido-5-acylamino form of 8-epilegionaminic acid [8eLeg5R7Ac, acylated at C5 with (S)-3-hydroxybutanoyl or acetyl (1:1)], the elucidated structure of the K63 type capsule was found to include a derivative of 5,7-diamino-3,5,7,9-tetradeoxy-d-glycero-d-galacto-non-2-ulosonic (legionaminic) acid, Leg5Ac7R, where R is either (S)-3-hydroxybutanoyl or an acetyl group (∼1:1 ratio). This finding is consistent with the presence of the lgaABCHIFG gene module for Leg5Ac7R biosynthesis in the KL63 gene cluster at the capsular polysaccharide (CPS) biosynthesis K locus in the LUH5551 genome. The glycosyltransferases (Gtrs) and Wzy polymerase encoded by KL63 were assigned to linkages in the linear K63 tetrasaccharide unit and linkage of the K63 units.

Multi-scale utilization of lignin: A catalytic hydrogenation strategy based on catechyl lignin nanoparticles

With an abundance of oxygen-containing groups on the hydrophilic shell of lignin nanoparticles (LNPs), this biomaterial can serve as a catalytic support to adsorb and load metals. Herein, catechyl lignin oligomers from castor seed coats (Cas) were extracted via solvothermal pretreatment and prepared as LNPs using the solvent shifting method. Pd2+ ions were then stabilized and reduced in situ on the surface of LNPs, which were further utilized for the catalyzed hydrogenation of lignin-derived aldehydes. Due to the homogeneous building units and linear linkages, the lignin oligomers from Cas exhibited superior self-assembly capacity with a lower π-π interaction energy than those from conventional lignocelluloses, resulting in a high yield of LNPs with a smooth surface. The high content of phenolic hydroxyl groups in catechyl-dominant LNPs resulted in efficient Pd2+ ions adsorption via chemisorption of monomolecular layer and a partial reduction of the Pd2+ ions into metallic states. In addition, the Cas-derived Pd/LNPs exhibited exceptional catalytic activity for the hydrogenation of lignin-derived aldehydes with high selectivity to alcohols under mild conditions. This could be attributed to the interaction preference of the reaction substrate according to the construction of LNPs: strong hydrogen bond between the aldehyde group of the substrate and the hydrophilic shell of LNPs, as well as the hindered π-π interactions between the benzene ring of the substrate and the hidden hydrophobic core of LNPs. This study, therefore, successfully employed lignin with a broad range of molecular weights from oligomers to monomers, paving the way for a comprehensive lignin biorefining industry.

A network coupling approach to detecting hierarchical linkages between science and technology

AbstractDetecting science–technology hierarchical linkages is beneficial for understanding deep interactions between science and technology (S&T). Previous studies have mainly focused on linear linkages between S&T but ignored their structural linkages. In this paper, we propose a network coupling approach to inspect hierarchical interactions of S&T by integrating their knowledge linkages and structural linkages. S&T knowledge networks are first enhanced with bidirectional encoder representation from transformers (BERT) knowledge alignment, and then their hierarchical structures are identified based on K‐core decomposition. Hierarchical coupling preferences and strengths of the S&T networks over time are further calculated based on similarities of coupling nodes' degree distribution and similarities of coupling edges' weight distribution. Extensive experimental results indicate that our approach is feasible and robust in identifying the coupling hierarchy with superior performance compared to other isomorphism and dissimilarity algorithms. Our research extends the mindset of S&T linkage measurement by identifying patterns and paths of the interaction of S&T hierarchical knowledge.

OTULIN protects the intestinal epithelium from apoptosis during inflammation and infection

The intestinal epithelium is a single cell layer that is constantly renewed and acts as a physical barrier that separates intestinal microbiota from underlying tissues. In inflammatory bowel disease (IBD) in humans, as well as in experimental mouse models of IBD, this barrier is impaired, causing microbial infiltration and inflammation. Deficiency in OTU deubiquitinase with linear linkage specificity (OTULIN) causes OTULIN-related autoinflammatory syndrome (ORAS), a severe inflammatory pathology affecting multiple organs including the intestine. We show that mice with intestinal epithelial cell (IEC)-specific OTULIN deficiency exhibit increased susceptibility to experimental colitis and are highly sensitive to TNF toxicity, due to excessive apoptosis of OTULIN deficient IECs. OTULIN deficiency also increases intestinal pathology in mice genetically engineered to secrete excess TNF, confirming that chronic exposure to TNF promotes epithelial cell death and inflammation in OTULIN deficient mice. Mechanistically we demonstrate that upon TNF stimulation, OTULIN deficiency impairs TNF receptor complex I formation and LUBAC recruitment, and promotes the formation of the cytosolic complex II inducing epithelial cell death. Finally, we show that OTULIN deficiency in IECs increases susceptibility to Salmonella infection, further confirming the importance of OTULIN for intestinal barrier integrity. Together, these results identify OTULIN as a major anti-apoptotic protein in the intestinal epithelium and provide mechanistic insights into how OTULIN deficiency drives gastrointestinal inflammation in ORAS patients.

Taxation, democracy, and inequality in Sub‐Saharan Africa: Relevant linkages for sustainable development goals

AbstractGiven that the linear linkage between taxation and income inequality remains unclear, especially in Sub‐Saharan African countries, it is critical to explore how the redistribution channel of the tax system could mitigate income inequality within democratic institutions. Using the instrumental variable approach for robust analysis, this study explores the panel dataset of 42 Sub‐Saharan African countries from 1996–2014. The following findings are documented. First, both unconditional linkages between taxation and democracy overwhelmingly reduce income inequality. Second, harnessing democracy with taxation has a net effect that reduces income inequality. Overall, this study establishes that a strong democratic system strengthens the tax system for an income redistribution strategy to enhance income equality. This study is relevant for the achievement of Sustainable Development Goal (SGD) 1 on poverty reduction, SDG 10 on inequality, and SDG 16 on strong institutions.Related ArticlesGatchair, Sonia D. 2015. “Ideology and Interests in Tax Administration Reform in Jamaica.” Politics & Policy 43(6): 887–913. https://doi.org/10.1111/polp.12139.Nchofoung, Tii, Simplice Asongu, Vanessa Tchamyou, and Ofeh Edoh. 2022. “Gender, Political Inclusion, and Democracy in Africa: Some Empirical Evidence.” Politics & Policy 51(1): 137–55. https://doi.org/10.1111/polp.12505.Wang, Yingyao. 2017. “Why Tax Policy Is Not Politics in China: Public Finance and China's Changing State‐Society Relations.” Politics & Policy 45(2): 194–223. https://doi.org/10.1111/polp.12200.

Linear and non-linear linkage between human capital and foreign direct investment inflows into APEC countries: an evidence from panel data

Linear and non-linear linkage between human capital and foreign direct investment inflows into APEC countries: an evidence from panel data

Foaming epoxy-amine-carbamate: The effect of different neat amines on rheological and cellular morphology

The use of carbamate to foam epoxy depends significantly on the precured modulus to stabilize the cellular structure. The optimum precured modulus is developed from the reaction of epoxy resin and the neat amine. The selection of the neat amine relies on its reaction temperature with epoxy, which is required to be below the decomposition temperature of carbamate. This study investigates the effect of three different neat amines on the rheological behavior of foaming epoxy-carbamate-amine. They are bisphenol-A diglycidyl ether epoxy (DGEBA), isophorone diamine carbamate (IDPA.CO2), N-aminoethylpiperazine (AEP), 2,4-Diamino-1-methyl-cyclohexan (DMC) and isophorone diamine (IDPA). The mixtures of DGEBA-amine-carbamate are filled in 25% and 75% of the volume of a closed mold. Precuring is carried out at 60°C for 2 h. The foaming and complete curing are conducted at 180°C for 1 h. Having H-active at piperazine, AEP reacts with DGEBA faster and develops a higher precured modulus compared to DMC and IDPA. It is important to note that DGEBA-AEP-IDPA.CO2 exhibits viscoelastic behavior beyond 138°C, seen by its rheological storage modulus lower than loss modulus and its tan delta larger than 1. The reaction between DGEBA and the H-active piperazine of AEP leads only to linear linkage and is unable to further crosslink compared to the primary amine (-NH2). This results in a lower glass transition temperature Tg of DGEBA-AEP-IPDA.CO2. The effect of amine on foaming is more obviously at 25% filling level. DGEBA-AEP-IPDA.CO2 has more spherical and homogeneous cellular structure and the density of 285 kg/m3. Having quite similar chemical structure, both DGEBA-DMC-IPDA.CO2 and DGEBA-IPDA-IPDA.CO2 produce the epoxy foams having cell-interconnection and coalescence; their densities are also similar 301 kg/m3 and 305 kg/m3, respectively. All the foams are closed-cell at 75% of filling level. The cell morphologies are well reflecting the foaming modulus and tan delta behavior.

Linkage and Stereochemistry Characters of Phenolic Antioxidant Product Formation.

The present study developed a smart and novel strategy to elucidate the linkage and stereochemistry characters during phenolic antioxidant product formation. A series of phenolic isomers or analogues were treated with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical, to create 16 antioxidant dimerization reactions in aqueous solution. The products were rapidly identified by ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass-spectrometry. Through a systematic function-structure relationship analysis of these reactions and theoretical calculations, it is concluded that the phenolic antioxidant product is formed via linear linkage or furanocyclic linkage. The linear linkage is fulfilled via a radical coupling and controlled by the O-O linkage exclusion, meta-linkage exclusion, and catechol-activated principles. However, when an exocyclic π-bond conjugates with the phenolic core and is affixed at the -OH para-position, the furanocyclic linkage may occur via a subsequent intramolecular Michael addition. The intramolecular addition always lacks Re-attack to show "α,β diastereoselectivity." The α,β diastereoselectivity is the stereochemistry character of furanocyclic linkage during phenolic antioxidant product formation. All these novel findings can benefit not only the field food science but also other fields as well.

Capital Inflows, Inflation, and the Exchange Rate Volatility: An Investigation for Linear and Nonlinear Causal Linkages

This paper empirically examines the effect of foreign capital inflows on domestic price levels, monetary expansion, and the exchange rate volatility for Pakistan using linear and nonlinear causality tests. The key message emerging from the analysis is that there is a significant inflationary impact of capital inflows, in particular during the period of surges in capital inflows. Specifically, we find evidence of a significant nonlinear Granger causality running from capital inflows to the change in domestic prices. We also show that domestic prices are nonlinearly caused (in Granger sense) by the growth of domestic debt and money supply-to-GDP ratio. Our results, however, suggest that the market interest rate and the nominal exchange rate do not have significant relationships with domestic prices. The findings suggest that there is a need to manage the capital inflows in such a way that they should neither create an inflationary pressure in the economy nor fuel the exchange rate volatility. JEL Classification: C22, C32, F21, F31, F32 Keywords: Capital Inflows, Inflationary Pressures, the Exchange Rate Volatility, Monetary Expansion, Nonlinear Dynamics

Preparation of activated lignin with high hydroxyl content using lewis acid as demethylation reagent

Activation of lignin by demethylation for improving the reactivity has attracted extensive attentions. However, it still faces many challenges, such as the unsatisfied increase of hydroxyl content and the undesired cracking of linear linkages. Here, the efficient demethylations for significantly increasing the hydroxyl content and protecting the structure of industrial lignin were explored using lewis acid as modification reagent. As BBr3 was used, the phenolic hydroxyl content (Ar-OH) was increased by 80.65 %, but the lignin structure might be destroyed. About 75 % of the β-O-4 linkages could be fortunately retained by using AlCl3. This method could also be used for the demethylation of alkaline poplar lignin with up to 171.67 % increase of Ar-OH (from 1.80 to 4.89 mmol/g). After activation, the antioxidant properties were improved 4.64-fold and 2.58-fold for 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, respectively. This work would provide a theory guidance for activation of lignin and facilitate its high-value application.

Italian Diasporic Studies: The Then and Now

Italian Diasporic Studies: The Then and Now

Prostate Cancer Transcriptomic Regulation by the Interplay of Germline Risk Alleles, Somatic Mutations, and 3D Genomic Architecture.

Many prostate cancer germline risk alleles are enriched in the noncoding regions of the genome and are hypothesized to regulate transcription. We present a 3D genomics framework to unravel risk SNP function and describe the widespread germline-somatic interplay in transcription control. This article is highlighted in the In This Issue feature, p. 2711.