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Lyme disease is the most prevalent arthropod-borne infection in the United States. The etiological agent, Borreliella (or Borrelia ) burgdorferi , is maintained in nature through an enzootic cycle involving a tick vector and a mammalian host. RpoS, the master regulator of differential gene expression, plays a crucial role in tick transmission and mammalian infection of B. burgdorferi . This study reveals a positive feedback loop between RpoS and a Fur/PerR homolog. Elucidating this regulatory network is essential for identifying potential therapeutic targets to disrupt B. burgdorferi ’s enzootic cycle. The findings also have broader implications for understanding the regulation of RpoS and Fur/PerR family in other bacteria.

Engineered glyphosate resistance is the most widely adopted genetically modified trait in agriculture, gaining widespread acceptance by providing a simple robust weed control system. However, extensive and sustained use of glyphosate as a sole weed control mechanism has led to field selection for glyphosate-resistant weeds and has induced significant population shifts to weeds with inherent tolerance to glyphosate. Additional weed control mechanisms that can complement glyphosate-resistant crops are, therefore, urgently needed. 2,4-dichlorophenoxyacetic acid (2,4-D) is an effective lowcost, broad-spectrum herbicide that controls many of the weeds developing resistance to glyphosate. We investigated the substrate preferences of bacterial aryloxyalkanoate dioxygenase enzymes (AADs) that can effectively degrade 2,4-D and have found that some members of this class can act on other widely used herbicides in addition to their activity on 2,4-D. AAD-1 cleaves the aryloxyphenoxypropionate family of grass-active herbicides, and AAD-12 acts on pyridyloxyacetate auxin herbicides such as triclopyr and fluroxypyr. Maize plants transformed with an AAD-1 gene showed robust crop resistance to aryloxyphenoxypropionate herbicides over four generations and were also not injured by 2,4-D applications at any growth stage. Arabidopsis plants expressing AAD-12 were resistant to 2,4-D as well as triclopyr and fluroxypyr, and transgenic soybean plants expressing AAD-12 maintained field resistance to 2,4-D over five generations. These results show that single AAD transgenes can provide simultaneous resistance to a broad repertoire of agronomically important classes of herbicides, including 2,4-D, with utility in both monocot and dicot crops. These transgenes can help preserve the productivity and environmental benefits of herbicide-resistant crops.

Bacillus thuringiensis (Bt) Cry34Ab1/Cry35Ab1 are binary insecticidal proteins that are co-expressed in transgenic corn hybrids for control of western corn rootworm, Diabrotica virgifera virgifera LeConte. Bt crystal (Cry) proteins with limited potential for field-relevant cross-resistance are used in combination, along with non-transgenic corn refuges, as a strategy to delay development of resistant rootworm populations. Differences in insect midgut membrane binding site interactions are one line of evidence that Bt protein mechanisms of action differ and that the probability of receptor-mediated cross-resistance is low. Binding site interactions were investigated between Cry34Ab1/Cry35Ab1 and coleopteran active insecticidal proteins Cry3Aa, Cry6Aa, and Cry8Ba on western corn rootworm midgut brush border membrane vesicles (BBMV). Competitive binding of radio-labeled proteins to western corn rootworm BBMV was used as a measure of shared binding sites. Our work shows that (125)I-Cry35Ab1 binds to rootworm BBMV, Cry34Ab1 enhances (125)I-Cry35Ab1 specific binding, and that (125)I-Cry35Ab1 with or without unlabeled Cry34Ab1 does not share binding sites with Cry3Aa, Cry6Aa, or Cry8Ba. Two primary lines of evidence presented here support the lack of shared binding sites between Cry34Ab1/Cry35Ab1 and the aforementioned proteins: 1) No competitive binding to rootworm BBMV was observed for competitor proteins when used in excess with (125)I-Cry35Ab1 alone or combined with unlabeled Cry34Ab1, and 2) No competitive binding to rootworm BBMV was observed for unlabeled Cry34Ab1 and Cry35Ab1, or a combination of the two, when used in excess with (125)I-Cry3Aa, or (125)I-Cry8Ba. Combining two or more insecticidal proteins active against the same target pest is one tactic to delay the onset of resistance to either protein. We conclude that Cry34Ab1/Cry35Ab1 are compatible with Cry3Aa, Cry6Aa, or Cry8Ba for deployment as insect resistance management pyramids for in-plant control of western corn rootworm.

Although benzbromarone is a highly potent inhibitor of URAT1, the toxicity of its metabolite has led to the restricted use. In this study, to decrease its toxicity, thirteen benzbromarone derivatives were designed and synthesized via blocking metabolic site. Among them, most of the compounds had moderate to strong inhibitory activity against URAT1, with IC 50 values ranging from 0.041 ± 0.010 μM to 3.208 ± 0.458 μM. In particular, compound 30 demonstrated the most potent URAT1-inhibitory activity (IC 50  = 0.041 ± 0.010 μM), which is nearly seven-fold enhanced over BBR (IC 50  = 0.278 ± 0.053 μM). Importantly, it displayed a favorable bioavailability of 75.2%. As demonstrated by the in vitro and in vivo experiments, no reported toxic metabolites were found and the risk of potential liver toxicity was low.

Inositol 1,3,4,5,6-pentakisphosphate 2-kinase, an enzyme encoded by the gene IPK1, catalyzes the terminal step in the phytic acid biosynthetic pathway. We report here the isolation and characterization of IPK1 cDNA and genomic clones from maize (Zea mays). DNA Southern-blot analysis revealed that ZmIPK1 in the maize genome constitutes a small gene family with two members. Two nearly identical ZmIPK1 paralogs, designated as ZmIPK1A and ZmIPK1B, were identified. The transcripts of ZmIPK1A were detected in various maize tissues, including leaves, silks, immature ears, seeds at 12 d after pollination, midstage endosperm, and maturing embryos. However, the transcripts of ZmIPK1B were exclusively detected in roots. A variety of alternative splicing products of ZmIPK1A were discovered in maize leaves and seeds. These products are derived from alternative acceptor sites, alternative donor sites, and retained introns in the transcripts. Consequently, up to 50% of the ZmIPK1A transcripts in maize seeds and leaves have an interrupted open reading frame. In contrast, only one type of splicing product of ZmIPK1B was detected in roots. When expressed in Escherichia coli and subsequently purified, the ZmIPK1 enzyme catalyzes the conversion of myo-inositol 1,3,4,5,6-pentakisphosphate to phytic acid. In addition, it is also capable of catalyzing the phosphorylation of myo-inositol 1,4,6-trisphosphate, myo-inositol 1,4,5,6-tetrakisphosphate, and myo-inositol 3,4,5,6-tetrakisphosphate. Nuclear magnetic resonance spectroscopy analysis indicates that the phosphorylation product of myo-inositol 1,4,6-trisphosphate is inositol 1,2,4,6-tetrakisphosphate. Kinetic studies showed that the Km for ZmIPK1 using myo-inositol 1,3,4,5,6-pentakisphosphate as a substrate is 119 μM with a Vmax at 625 nmol/min/mg. These data describing the tissue-specific accumulation and alternative splicing of the transcripts from two nearly identical ZmIPK1 paralogs suggest that maize has a highly sophisticated regulatory mechanism controlling phytic acid biosynthesis.

In , the Lyme disease pathogen, differential gene expression is primarily controlled by the alternative sigma factor RpoS (σ ). Understanding how RpoS levels are regulated is crucial for elucidating how is maintained throughout its enzootic cycle. Our recent studies have shown that a homolog of Fur/PerR repressor/activator, BosR, functions as an RNA-binding protein that controls the mRNA stability. However, the mechanisms of regulation of BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we revealed a positive feedback loop between RpoS and BosR, where RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion of significantly reduced BosR levels, while artificial induction of resulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affect mRNA levels but instead modulates the turnover rate of the BosR protein. Furthermore, we demonstrated that environmental cues do not directly influence expression but instead induce transcription and RpoS production, thereby enhancing BosR protein levels. This discovery adds a new layer of complexity to the RpoN-RpoS pathway and suggests the need to re-evaluate the factors and signals previously believed to regulate RpoS levels through BosR.

Tricyclic antidepressant (TCA) toxicity is a leading cause of death from intentional drug poisoning. Monoclonal and polyclonal antibody Fab fragments specific for the tricyclic antidepressant, desipramine (DMI), reverse acute drug toxicity, but the high dose of Fab itself produces adverse effects. Therefore smaller antibody fragments consisting only of the variable regions of the heavy and light chains of DMI-specific monoclonal antibodies, joined by a synthetic peptide linker, were constructed genetically. Anti-desipramine antibody Fv fragments from two independent murine hybridoma cell lines were cloned and characterized. Subsequently, the single-chain Fv fragments (scFv) were constructed, produced and purified using Escherichia coli and Pichia pastoris expression systems. In bacteria, scFv was expressed at high levels as inclusion bodies. After solubilization and refolding in a redox buffer, active scFv was affinity purified at levels from 50 to 100 mg/l in large scale (1-25 liters) production. In yeast, scFv was expressed as a secreted and active form at approximately 50 mg/l in shake flasks. The recombinant scFv fragments retained similar binding affinity as the corresponding monoclonal Fab fragments for DMI. The affinity of scFv for DMI (K $\\sb{\\rm A}=2.3\\times 10\\sp8$M $\\sp{-1}$ ) was only slightly lower than that of the parental Fab fragment (K $\\sb{\\rm A}=5.5\\times 10\\sp8$M $\\sp{-1}$ ), as measured by surface plasmon resonance. The scFv was stable at 4 $\\sp\\circ$ C for greater than 6 months, but lost activity at higher temperatures. The scFv altered DMI pharmacokinetics by rapidly redistributing the drug from tissues into serum, thus quickly reversing DMI toxicity in rats. A disulfide-stabilized scFv (dcFv) was constructed based on the computer models of Fv structure, and expressed in P. pastoris as a secreted and active protein. The dcFv construct showed improved stability at 37 $\\sp\\circ$ C in rat serum, but a reduced affinity for DMI (K $\\sb{\\rm A}=1\\times 10\\sp8$M $\\sp{-1}).$The data indicate that the anti-DMI recombinant Fv fragments retain full activity. The pharmacokinetic effect of scFv on DMI distribution suggests that it may be a useful antidote for the treatment of TCA overdose and that rational design of desirable attributes may further enhance the scFv therapeutic properties.

Building a trading market can promote energy conservation provided that the trading method is determined. Energy consumption for heat supply is huge. Tianjin Municipal Government is planning to establish an energy efficiency trading platform for district heating taking into consideration the experience in carbon trading market and specific situation in Tianjin. This paper presented an in-depth analysis of the district heating industry in Tianjin municipality, and identified the potentials of energy saving and carbon dioxide emissions reduction. Since energy efficiency was closely related to different heating source technologies, baselines were determined for boiler plants and thermal power plants respectively. Three scenarios were discussed for baseline determination. 472 boiler plants were surveyed and operational data relating to energy consumption were collected. Through data analysis, 27 boiler plants which have reasonable recorded energy consumption values were chosen as samples. By analyzing the dataset and referring to the related standards, method of determining the baseline for district heating carbon market was established. Finxally, the baseline for boiler plant was determined to be 52.0 kgce/GJ, and that for thermal power plant was 43.0 kgce/GJ in 2011. Carbon abatement against the baselines above was calculated and considerable carbon dioxide emissions reduction could be achieved.

HighlightsAn all-wood hydrogel was synthesized via a simply Hofmeister effect without the use of any chemical cross-linking agent.The all-wood hydrogel shows a high tensile strength of 36.5 MPa, a strain up to ~ 438%, and good conductivity, and can accurately distinguish diverse large or subtle human movements.The all-wood hydrogel has good recyclable, biodegradable, and adjustable mechanical properties.Wood-based hydrogel with a unique anisotropic structure is an attractive soft material, but the presence of rigid crystalline cellulose in natural wood makes the hydrogel less flexible. In this study, an all-wood hydrogel was constructed by cross-linking cellulose fibers, polyvinyl alcohol (PVA) chains, and lignin molecules through the Hofmeister effect. The all-wood hydrogel shows a high tensile strength of 36.5 MPa and a strain up to ~ 438% in the longitudinal direction, which is much higher than its tensile strength (~ 2.6 MPa) and strain (~ 198%) in the radial direction, respectively. The high mechanical strength of all-wood hydrogels is mainly attributed to the strong hydrogen bonding, physical entanglement, and van der Waals forces between lignin molecules, cellulose nanofibers, and PVA chains. Thanks to its excellent flexibility, good conductivity, and sensitivity, the all-wood hydrogel can accurately distinguish diverse macroscale or subtle human movements, including finger flexion, pulse, and swallowing behavior. In particular, when “An Qi” was called four times within 15 s, two variations of the pronunciation could be identified. With recyclable, biodegradable, and adjustable mechanical properties, the all-wood hydrogel is a multifunctional soft material with promising applications, such as human motion monitoring, tissue engineering, and robotics materials.

Background Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes. Methods The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on ‘‘TyG index’’ and \"stroke\" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0. Results A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22–1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I 2  = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19–1.89) and increased risk of mortality (OR 1.40 95% CI 1.14–1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88–1.43) and neurological worsening (OR: 1.76; 95% CI 0.79–3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I 2  = 77.20%). Conclusions TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.