Residual Activity Research Articles

A polyethylene glycol derivatized laccase with improved thermal resistance

Laccases are versatile and relatively accessible catalysts with practical/industrial applications. Their protein structure entails limited stability under non-native conditions, especially such as those that would be required for industrial applications. Here, the derivatization of a laccase from Sclerotinia sclerotiorum is reported, using a (methyl-PEG12)3-PEG4)-N-succinimide ester – known as trimethyl-PEG-NHS or shortly TMS(PEG)12 – to improve the thermostability of the enzyme. PEGylated versions of the laccase are characterized by gel electrophoresis, size-exclusion chromatography, catalytic parameters, and thermal stability. A protocol for PEGylation is identified, that allows for a 50% increase in residual activity for the PEGylated laccase compared to the native enzyme, when the activity is tested after incubation at 50 °C for up to two hours.

Assessment of Residual [99mTc]Tc-Tetrofosmin Activity in Routine Nuclear Medicine Practice at Hospital Kuala Lumpur.

Myocardial perfusion imaging using the radiopharmaceutical [99mTc]Tc-tetrofosmin plays a crucial role in diagnosing cardiac conditions. However, variations in the residual activity of [99mTc]Tc-tetrofosmin in plastic syringes after administration may impact imaging quality and patient safety. This study aimed to evaluate the residual activity of [99mTc]Tc-tetrofosmin in plastic syringes after administration during routine nuclear medicine procedures at Hospital Kuala Lumpur, assessing compliance with department protocols and variability among different syringe brands. Methods: A single-center prospective observational study was conducted using stratified quota sampling, encompassing 396 samples across 3 syringe brands (SJ, BD, and Ciringe). Residual activity was measured immediately after administration, and statistical analysis was performed to compare brands and assess compliance with the department dosage protocol range of 333-555 MBq. Results: All injected activities aligned with the department protocol dose, with a mean effective activity of 451.23 ± 30.73 MBq and a mean residual activity of 12.63% ± 4.73%. However, variability in residual activity was observed among syringe brands. BD exhibited the highest mean residual activity (16.45%), significantly differing from SJ (9.95%) and Ciringe (11.50%) (P < 0.001). Conclusion: Rigorous syringe selection is crucial in myocardial perfusion imaging procedures to minimize residual activity and ensure compliance with dosimetry standards, emphasizing the importance of integrating pharmacy practices into nuclear medicine protocols. Standardized protocols and quality assurance measures are essential to optimize imaging outcomes and prioritize patient safety. These findings highlight the importance of ongoing monitoring and interdisciplinary collaboration to navigate residual activity management effectively in routine nuclear medicine practice.

Development of an automated method for in-house production of sodium 18F-fluoride for injection: process validation as a step toward routine clinical application

BackgroundSodium 18F-fluoride for injection can be easily cyclotron-produced and purified, as a simple inorganic salt, by adsorption/desorption onto an anion-exchange cartridge and then dispensed for clinical use. Since the clinical demand for this radiopharmaceutical is constantly increasing, this study aimed to design and develop a simple, fully automated method for the in-house, rapid, and efficient processing and dispensing of injectable solutions of Sodium 18F-fluoride without the need of a synthesis module and disposable kit, but using only the dispensing unit.ResultsA new simple method for the efficient routine production of injectable solutions of [18F]NaF was developed through a straightforward modification of the commercial dispenser Clio (Comecer S.p.A., Italy) and without the need of a synthesis module. The full production, processing and dispensing of [18F]NaF were entirely carried out on the same batch using only the dispensing module. Process validation was carried according to GMP guidelines to ensure consistency of [18F]NaF quality with international standards. The final radiopharmaceutical met all quality criteria specified by Ph. Eur. and chemical, radionuclidic and radiochemical impurities were significantly below the required limits.ConclusionA new simple and reliable procedure developed for the preparation and dispensing of injectable [18F]NaF in less than 10 min with a radiochemical yield > 97% (decay corrected) has been successfully developed. Notably, the proposed method also allows the preparation of [18F]NaF using the residual fluorine-18 activity remaining after a [18F]FDG production run, thus making it immediately accessible to patients for further PET imaging investigations.

Chimeric CYP21A1P/CYP21A2 Genes in 21-Hydroxylase Deficiency Detected by Long-Read Sequencing and Phenotypes Correlation.

21-Hydroxylase deficiency (21-OHD) is caused by pathogenic variants in CYP21A2. High homology between CYP21A2 and its pseudogene CYP21A1P causes mismatches, leading to deletions and CYP21A1P/CYP21A2 chimeras. To detect chimeric CYP21A1P/CYP21A2 in 21-OHD patients using long-read sequencing (LRS) and analyze genotype-phenotype correlations. From 2015 to 2023, 869 21-OHD patients were enrolled at Peking Union Medical College Hospital, with 113 identified harboring CYP21A2 large deletion. Long-range PCR and LRS were used to identify the types of CYP21A1P/CYP21A2 chimeric. Haplotype analysis explored founder effects, and in vitro assays assessed the functional impact of novel mutations. Clinical data were retrospectively collected and patients were classified into 4 groups based on genotypes and residual enzyme activity to study genotype-phenotype correlations. Ten types of chimeric CYP21A1P/CYP21A2 genes were identified across 119 alleles, including a novel type, CH-10. The most common, CH-1, accounted for 50.4% of all types. Haplotype analysis of 24 SNPs within CYP21A1P/CYP21A2 CH-1 revealed 25 haplotypes, with haplotype 11 being the most prevalent. Variants p.L100P and p.L301V of CYP21A2 showed enzyme activities of 1.36 ± 0.44% or 1.63 ± 0.19% for 17-hydroxyprogesterone to 11-deoxycortisol, and 1.36 ± 0.58% or 3.99 ± 1.09% for progesterone to 11-deoxycorticosterone, respectively, linked to the simple virilizing type. Genotype-phenotype consistency rates were 78.6% to 84% across the 4 groups. LRS is a comprehensive genetic testing method for 21-OHD patients, effectively detecting both CYP21A2 gene variants and CYP21A1P/CYP21A2 chimeric gene types. This study expands the CYP21A2 variant spectrum by identifying a novel chimera. Haplotype analysis revealed diverse haplotypes for each chimeric gene type, suggesting the absence of a common founder effect. The strong genotype-phenotype correlation aids genetic counseling and supports personalized treatment.

Functional near-infrared spectroscopy for the assessment and treatment of patients with disorders of consciousness

BackgroundAdvances in neuroimaging have significantly enhanced our understanding of brain function, providing critical insights into the diagnosis and management of disorders of consciousness (DoC). Functional near-infrared spectroscopy (fNIRS), with its real-time, portable, and noninvasive imaging capabilities, has emerged as a promising tool for evaluating functional brain activity and nonrecovery potential in DoC patients. This review explores the current applications of fNIRS in DoC research, identifies its limitations, and proposes future directions to optimize its clinical utility.AimThis review examines the clinical application of fNIRS in monitoring DoC. Specifically, it investigates the potential value of combining fNIRS with brain-computer interfaces (BCIs) and closed-loop neuromodulation systems for patients with DoC, aiming to elucidate mechanisms that promote neurological recovery.MethodsA systematic analysis was conducted on 155 studies published between January 1993 and October 2024, retrieved from the Web of Science Core Collection database.ResultsAnalysis of 21 eligible studies on neurological diseases involving 262 DoC patients revealed significant findings. The prefrontal cortex was the most frequently targeted brain region. fNIRS has proven crucial in assessing brain functional connectivity and activation, facilitating the diagnosis of DoC. Furthermore, fNIRS plays a pivotal role in diagnosis and treatment through its application in neuromodulation techniques such as deep brain stimulation (DBS) and spinal cord stimulation (SCS).ConclusionAs a noninvasive, portable, and real-time neuroimaging tool, fNIRS holds significant promise for advancing the assessment and treatment of DoC. Despite limitations such as low spatial resolution and the need for standardized protocols, fNIRS has demonstrated its utility in evaluating residual brain activity, detecting covert consciousness, and monitoring therapeutic interventions. In addition to assessing consciousness levels, fNIRS offers unique advantages in tracking hemodynamic changes associated with neuroregulatory treatments, including DBS and SCS. By providing real-time feedback on cortical activation, fNIRS facilitates optimizing therapeutic strategies and supports individualized treatment planning. Continued research addressing its technical and methodological challenges will further establish fNIRS as an indispensable tool in the diagnosis, prognosis, and treatment monitoring of DoC patients.

Xylanase of Bacillus sp. NIORKP76 grown under solid state fermentation: production, purification, characterization and its saccharification potential

Microbial xylanases are xylan hydrolyzing enzymes which has congregated attention due to their immense potential in many industries. The current study is focused on xylanase from bacterial isolate identified as Bacillus sp. NIORKP76 on an inexpensive agro-industrial waste (wheat bran) under solid-state fermentation. The isolate showed maximum xylanase production in growth medium supplemented with phosphate, NaCl and NH4Cl at 64 mM, 15 mg/mL and 0.3 mg/mL respectively which was maintained at 1:3 substrate to moisture ratio (w/v). Using optimized conditions, the maximum xylanase production in wheat bran was achieved in 72 h at room temperature 28 ± 2 °C. Xylanase exhibited pH optimum of 8.0 and retained 92% of its residual activity after 24 h incubation at pH 8. Xylanase displayed optimum activity at 60 °C, whereas it remained unhindered even after 12 h of incubation period at 30 and 40 °C. The xylanase isolated in this study was purified to homogeneity with a molecular weight of approximately 28 kDa. Xylanase from Bacillus sp. NIORKP76 was potentially converting agro-residues into biofuel feedstock. Pretreated wheat bran produced the highest yield fermentable sugars (141 mg/g), after 8 h incubation with 5 U/g xylanase and at 40 °C.

Design of a Peroxidase‐Based Gas Diffusion Electrode for Bioelectroenzymatic Applications

We report here the design and application of an all‐in‐one gas diffusion electrode (GDE) combined with surface immobilized horseradish peroxidase (HRP) capable of in situ generation of hydrogen peroxide (H2O2) from air and simultaneous oxidation of a model substrate (ABTS) within a single‐cell electrochemical reactor. Carboxyl‐functionalized multiwalled carbon nanotubes (MWCNT‐COOH) were employed as an electrocatalyst for oxygen reduction reaction producing 719 ± 97 µM h−1 H2O2 at −0.2 V (vs Ag/AgCl) as an electron acceptor for HRP. We investigated two immobilization strategies to obtain HRP‐modified biocathodes using covalent amide conjugation between primary amine groups of HRP and carboxyl groups of MWCNT‐COOH (GDE/MWCNT‐COOH/HRP) and entrapment into a cross‐linked pyrene‐modified linear poly(ethylenimine) matrix (GDE/MWCNT‐COOH/Py‐LPEI/HRP). Fourier transform infrared spectroscopy (FT‐IR) and scanning electron microscopy (SEM) were used to characterize such surface modifications. The apparent catalytic activity achieved by HRP‐modified biocathodes via either covalent conjugation or entrapment into a polymer film was 311 ± 31 U mg−1 and 174 ± 17 U mg−1, respectively, as compared to the activity of freely diffusing 188 ± 23 U mg−1. The interfaces were reused showing 55% and 82% residual activity after 5 consecutive cycles for GDE/MWCNT‐COOH/HRP and GDE/MWCNT‐COOH/Py‐LPEI/HRP, respectively. Our findings illustrate prospects for integrating GDE and surface‐bound peroxidases for H2O2‐dependent electroenzymatic reactions, offering a promising platform for diverse applications in bioelectrosynthesis.

Comprehensive chemical profile, angiotensin-I converting enzyme inhibitory and calcium chelation activity of rice wine lees and rice vinegar residues: A novel development strategy

Comprehensive chemical profile, angiotensin-I converting enzyme inhibitory and calcium chelation activity of rice wine lees and rice vinegar residues: A novel development strategy

Heterojunction of titanate nanotubes enhanced by curcumin: synthesis, characterization, and evaluation of hemolytic activity and cytotoxicity

Heterojunction of titanate nanotubes enhanced by curcumin: synthesis, characterization, and evaluation of hemolytic activity and cytotoxicity

Residual galactosylceramidase activity correlates with psychosine levels in GALC missense variants cell model of Krabbe disease

Residual galactosylceramidase activity correlates with psychosine levels in GALC missense variants cell model of Krabbe disease

Epidemiology and Genetic Traits of Carbapenemase-Producing Enterobacterales: A Global Threat to Human Health

Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided into three classes (A, B, and D) according to the Ambler classification system. Among these, KPC (class A), NDM, VIM, IMP (class B), and OXA-48-like (class D) represent the most important carbapenemases in terms of diffusion and clinical impact. CPE diffusion has been observed worldwide, with current endemicity in multiple territories around the world. In this context, the clonal spread and plasmid-mediated transmission of carbapenemases have contributed to the global spread of CPE worldwide and to the diffusion of carbapenemases among different Enterobacterales species. In recent years, novel molecules showing excellent in vitro and in vivo activity have been developed against CPE. However, the recent emergence of novel traits of resistance to these molecules has already been reported in several cases, mitigating the initial promising results. This review aims to provide an updated description of the major classes of carbapenemases, their global distribution, and future perspectives to limit the diffusion of CPEs.

Recessive Variants in PIGG Cause a Motor Neuropathy with Variable Conduction Block, Childhood Tremor, and Febrile Seizures: Expanding the Phenotype.

Biallelic variants in phosphatidylinositol glycan anchor biosynthesis, class G (PIGG) cause hypotonia, intellectual disability, seizures, and cerebellar features. We present 8 patients from 6 families with a childhood-onset motor neuropathy and neurophysiology demonstrating variable motor conduction block and temporal dispersion. All individuals had a childhood onset tremor, 5 of 8 had cerebellar involvement, and 6 of 8 had childhood febrile seizures. All individuals have biallelic PIGG variants, including the previously reported pathogenic variant Trp505*, plus 6 novel variants. Null enzyme activity is demonstrated via PIGO/PIGG double knockout system for Val339Gly and Gly19Glu, and residual activity for Trp505* due to read-through. Emm negative blood group status was confirmed in 1 family. PIGG should be considered in unsolved motor neuropathy. ANN NEUROL 2025;97:388-396.

Efficient secretory expression, purification, and characterization of lipase in Pseudomonas aeruginosa M18, with multifunctional applications in diagnostics.

Lipase (EC 3.1.1.3) is a crucial hydrolase with broad industrial and clinical applications. In this study, the lipA and lipH genes from Pseudomonas aeruginosa were cloned into the pBBR1MCS-2 vector and expressed under the regulation of the highly efficient BSFP_0720 promoter from Burkholderia stabilis FERMP-21014. This system allowed for efficient secretory expression in Pseudomonas aeruginosa without requiring an inducer. The recombinant lipase exhibited both lipase and cholesteryl esterase activities, making it suitable for triglyceride and cholesterol assay kits. Additionally, gene editing was used to knock out the endogenous cholesterol oxidase gene in Pseudomonas aeruginosa, eliminating cross-interference in different assay kits. High-density fermentation using glucose as the carbon source resulted in lipase activity reaching 68 kU/L and cholesteryl esterase activity reaching 214 kU/L after 30h of fermentation, representing a 356-fold increase compared to natural production. By combining ammonium sulfate precipitation, hydrophobic interaction chromatography, and anion exchange chromatography, a purity of 94.32% was achieved (as determined by CE-SDS). Accelerated stability tests showed that the lyophilized lipase retained over 96% residual activity after storage at 37°C for 21 days and at 45°C for 7 days, suggesting its suitability for long-term storage. The enzymatic properties of the lipase demonstrated resistance to common chemicals, high activity in buffers with pH values between 7 and 9, and short-term tolerance to high temperatures (60°C). These characteristics make the lipase highly adaptable for use in complex clinical samples and various industrial applications. The successful high-efficiency expression and multifunctional utility of this lipase highlight its significant commercial potential in diagnostics and other fields.

Putting the prime in priming: Using prime processing behavior to predict target structural processing.

Structural priming effects are widespread and heavily relied upon to assess structural representation and processing. Whether these effects are caused by error-driven implicit learning, residual activation, a combination of these, or some other learning mechanism remains to be established. The current study used preexisting data and a novel data analysis approach that links processing at the prime to later processing at the target to better understand the nature of structural priming. This novel analytic approach was applied to total reading times from a previously published structural priming study in comprehension, which provided processing measures of the structurally critical regions of prime reduced-relative clause sentences. These were then used as predictors in a series of hierarchical linear models where analogous processing measures at the target sentence regions served as outcome variables. Separate sets of models were run for prime-target pairs that had the same structure (i.e., abstract priming) and those that had the same structure and initial verb (i.e., a lexical boost). Prime-to-target processing relationships were observed for both types of prime-target pairs, but showed very different patterns. This provides support for the claim that abstract priming effects and the lexical boost are caused by different mechanisms. Additionally, the observed effects were positive and so do not support the error-driven learning prediction that processing difficulty at the prime should lead to greater facilitation at the target. Overall, this novel method provides a new tool for investigating structural priming and processing.

One-day dual-tracer examination in neuroendocrine neoplasms: a real advantage of low activity LAFOV PET imaging.

Somatostatin receptor (SSTR)-PET is crucial for effective treatment stratification of neuroendocrine neoplasms (NENs). In highly proliferating or poorly differentiated NENs, dual-tracer approaches using additional [18F]FDG PET can effectively identify SSTR-negative disease, usually requiring separate imaging sessions. We evaluated the feasibility of a one-day dual-tracer imaging protocol with a low activity [18F]FDG PET followed by an SSTR-PET using the recently introduced [18F]SiFAlin-TATE tracer in a long axial field-of-view (LAFOV) PET/CT scanner and its implications in patient management. Twenty NEN patients were included in this study. Initially, a low activity [18F]FDG PET was performed (0.5 ± 0.01 MBq/kg; PET scan 60min p.i.). After 4.2 ± 0.09h after completion of the [18F]FDG PET, a standard activity of [18F]SiFAlin-TATE was administered (3.0 MBq/kg; PET scan 90min p.i.). To ensure the quantification accuracy of the second scan, we evaluated the potential impact of residual [18F]FDG activity by segmenting organs with minimal physiological SSTR-tracer uptake, such as the brain and myocardium, and assessing the activity concentrations (ACTs) of tumor lesions. Residual tumor lesion ACTs of [18F]FDG were calculated by factoring fluorine-18 decay, identifying a maximum residual ACT of 15% (R15%). To account for increased [18F]FDG trapping over time, higher residual ACTs of 20% (R20%) were considered. These simulated [18F]FDG ACTs were compared with those measured in the second PET scan with [18F]SiFAlin-TATE. The influence of the dual-tracer PET/CT results on therapeutic strategies was evaluated. [18F]FDG cerebral uptake significantly decreased in the subsequent SSTR-PET (mean uptake [18F]FDG: SUVmean 6.0 ± 0.4; mean uptake in [18F]SiFAlin-TATE PET: SUVmean 0.2 ± 0.01; p < 0.0001); with similar results recorded for the myocardium. Simulated residual [18F]FDG ACTs represented only a minimal percentage of ACTs measured in the tumor lesions from the second PET scan (R15%: mean 5.2 ± 0.9% and R20%: mean 6.8 ± 1.2%), indicating only minimal residual activity of [18F]FDG that might interfere with the second PET scan using [18F]SiFAlin-TATE and preserved semi-quantification of the latter. Dual-tracer PET/CT findings directly influenced changes in therapy plans in eleven (55%) of the examined patients. LAFOV PET scanners enable a one-day dual-tracer protocol, providing diagnostic image quality while preserving the semi-quantification of two 18F-labeled radiotracers, potentially simplifying the assessment of tumor biology and improving the clinical patient management while reducing logistical challenges. Additionally, low-activity PET imaging facilitates one-day dual-tracer PET examinations.

Formulation of Ethyl Cellulose Nanoparticles Encapsulated with Osthole Provides Long-Lasting Plant Protection against a Major Pest Mite.

The broader use of botanical pesticides has been limited by shorter residual activity on plants, slower onset of action, and higher costs compared with conventional pesticides. These challenges could be overcome by the development of simple, cost-effective, and long-lasting preventive nanocomposites for botanical pesticides. In this study, we successfully developed a low-cost ethyl cellulose (EC)-based delivery system for the botanical pesticide osthole (OST), designed to provide extended preventive protection against Tetranychus urticae infestations. A comparative analysis of the three nanocomposites (graphene oxide (GO)-OST, EC-OST, and chitosan (CS)-OST) revealed that EC-OST exhibited superior thermal stability, UV resistance, controlled release of the OST payload, and strong acaricidal activity. The degradation of OST on leaf surfaces was reduced by encapsulation in EC, while its penetration into plant tissues was improved. When EC-OST was applied to leaves, an increase in T. urticae mortality, a reduction in reproduction and egg adhesion, and impairment of feeding behavior through extended searching and feeding times were observed. The peak occurrence of T. urticae infestation was delayed by 10 days following the preventive application of EC-OST, reducing plant damage and protecting the plants for more than 20 days. This nanoinsecticide allows for low-frequency OST application, reducing farmers' production costs, and increasing profitability, thereby offering great potential for promoting the use of botanical pesticides in plant protection.

Satsuma Orange Tolerance to Spring and Autumn Indaziflam Applications in Georgia

Citrus is a major crop in the SE US, with groves located primarily in Florida, but adapted cultivars have allowed for the expansion of commercial production into the Coastal Plains region of Georgia. Indaziflam, a cellulose biosynthesis inhibiting residual herbicide, controls numerous grass and broadleaf weed species. Research conducted in Georgia from 2020 to 2022 determined the optimal rate and tree response to indaziflam applications. Biannual treatments applied in April and November in established satsuma citrus groves included residual herbicides indaziflam, flumioxazin, diuron, pendimethalin, simazine, and norflurazon. The data indicated no negative impact on tree diameter growth over 30 months after application initiation. Indaziflam provided residual activity in the first year with &gt;80% weed control for bermudagrass and pink purslane and &gt;70% of cutleaf evening primrose, cutleaf geranium, and wild radish. Greater than 69% of weed control was maintained with indaziflam after sequential application for 2 years. All other herbicides provided inadequate residual weed control. Indaziflam PRE applied in citrus groves in Georgia can provide growers with a reliable herbicide option that has been proven to be safe for trees and season-long weed control.

Rhizobium Inoculants Mitigate Corn Herbicide Residual Effects on Soybean Germination

Corn residual herbicides offer a practical approach to comprehensive weed management throughout the growing season. However, the use of residual pre-emergence herbicides can have a negative impact on crops grown in succession or within a rotation. A study was carried out to determine the effect of the residual activity of selected corn herbicides on soybeans. The objective of the study was to evaluate the impact of these herbicides on the germination of inoculated soybean seeds. Experiments were conducted in greenhouse conditions to check the carryover effect on soybean germination. Treatment combinations of two pre-herbicides and two inoculants were applied: atrazine (2241 g ai ha−1), mesotrione (105 g ai ha−1), and Bradyrhizobium japonicum, Bradyrhizobium japonicum + Bacillus subtilis, respectively. A randomized complete block design evaluated six treatment combinations, including the control. All treatments, except uninoculated treatments, presented efficacy in reducing the carryover effects of corn residual herbicides on the germination of soybeans. An increase in final germination percentage was observed with Bradyrhizobium japonicum + Bacillus subtilis co-inoculation plus atrazine (24% increase) and Bradyrhizobium japonicum plus mesotrione treatment combinations (19% increase). Inoculating soybean seeds with rhizobium bacteria can reduce the carryover effects on the germination of soybean seeds grown in soil applied with atrazine and mesotrione.

The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse

Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, the activation of IRF5 downstream of human TLR7, TLR8 and TLR9, but the pathophysiological functions of this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block of TLR7/9-induced IRF5 activation, while loss of TASL leads to a strong but incomplete impairment, which depends on the cell type and TLR engaged. This residual IRF5 activity is ascribed to a previously uncharacterized paralogue, Gm6377, named here TASL2. Double knockout of TASL and TASL2 (TASLDKO) phenocopies SLC15A4-deficient feeble mice showing comparable impairment of innate and humoral responses. Consequently, TASLDKO mice fail to control chronic LCMV infection, while being protected in a pristane-induced SLE disease model. Our study thus demonstrates the critical pathophysiological role of SLC15A4 and TASL/TASL2 for TLR7/9-driven inflammatory responses, further supporting the therapeutic potential of targeting this complex in SLE and related diseases.

ATM Expression and Activation in Ataxia Telangiectasia Patients with and without Class Switch Recombination Defects

BackgroundAtaxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.MethodsA-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression of ATM and phosphorylated ATM (p-ATM) proteins compared to age-sex-matched healthy controls.ResultsIn severe A-T patients (n = 6), the majority (66.7%) had frameshift mutations, while 33.3% had nonsense mutations in the ATM gene. The mild group (n = 3) had two cases of splice errors and one missense mutation. All patients with CSR defect had elevated IgM serum levels, whereas all switched immunoglobulins were reduced in them. Expression of ATM and p-ATM proteins was significantly lower (p = 0.01) in all patients compared to healthy controls, both pre-and post- and post-radiation. Additionally, low ATM and p-ATM protein expression levels were linked with the clinical severity of patients but were not correlated with CSR defects.ConclusionExpression and activation of ATM protein were defective in A-T patients compared to healthy controls. Altered expression of ATM and p-ATM proteins may have potential clinical implications for prognostic evaluation and symptom severity assessment in individuals with A-T.