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PubMed2026

Deciphering the genomic landscape of novel Acinetobacter non-baumannii lineages causing neonatal septicemia: carbapenem resistance and virulence.

BACKGROUND: Acinetobacter non-baumannii (Anb) species are reported worldwide to cause infections in both adults and neonates, although less frequently than Acinetobacter baumannii. However, limited information is available on their genomic diversity, resistance mechanisms, and virulence potential. This study investigates novel Anb isolates causing neonatal septicemia in India to characterize their resistance and pathogenic traits. METHODS: Anb isolates from neonatal blood cultures (2007-2025) were identified by VITEK2 Compact system, MALDI-TOF MS, and Whole-genome sequencing (WGS). Antimicrobial susceptibility was tested by VITEK2. Genomic analysis included MLST, resistome, virulome, plasmid typing, integrons, and core-genome phylogeny analysis. In vitro and in vivo studies assessed pathogenic potential of Anb species. RESULTS: Anb infections were low (11%) among the neonates during the study period. WGS revealed 11 novel Sequence Types (STs) which include A. indicus, A. variabilis, A. schindleri, and A. bereziniae. Six out of these eleven Anbs harbored carbapenemases such as bla NDM-1 and/or bla OXA-58-like genes (bla OXA-58, bla OXA-420). bla NDM-1 was acquired via Tn125 transposon. ISAba125 was located upstream of bla NDM-1, and a conserved structure extending to IS91 family transposase was detected in bla NDM-1-harboring genomes. bla OXA-58-like genes were found to be associated with ISAba3. Most carbapenemases were likely located on chromosome. Class 1 integrons carrying multiple antimicrobial resistance genes (ARGs) and diverse plasmid replicase families were detected in Anbs. Core genome phylogeny showed that the study Anbs were not closely related to the global Anbs. In vitro virulence-associated assays (biofilm formation, surface motility, adherence/invasion, apoptosis) and in vivo lethality in murine infection model showed reduced pathogenicity, reinforcing earlier observations that Anb species are generally less virulent than A. baumannii. Several virulence factors (VFs) were detected; however, no clear correlation was observed between virulence genes, in vitro pathogenicity, and in vivo lethality. CONCLUSION: These results indicate the multifactorial nature of Anb pathogenicity and the current limitations of knowledge of its VFs. However, the presence of numerous VFs suggests a capacity to cause disease, particularly in vulnerable host populations such as neonates. Furthermore, the presence of multiple ARGs indicates a strong potential for persistence and dissemination in hospital environments with high antibiotic pressure. Overall, these findings underscore the importance of continued AMR surveillance, genome characterization and further investigations into Anb pathogenicity.

Acinetobacter non-baumannii↗

PubMed2026

Genomic insights into Aeromonas infections in diarrheal patients: high diversity, emerging resistance, and potential outbreak in Beijing.

BACKGROUND: Aeromonas species are ubiquitous aquatic bacteria that have emerged as significant foodborne enteric pathogens worldwide, yet their genomic landscape in clinical settings remains poorly delineated, particularly in Beijing. METHODS: To address this gap, we performed active surveillance for Aeromonas among 691 consecutive diarrheal outpatients in a Beijing district from January to December 2024. Isolates were recovered using enrichment culture coupled with PCR screening and identified by MALDI-TOF MS. Antimicrobial susceptibility was tested against 17 agents. Whole-genome sequencing was conducted on all isolates, enabling average nucleotide identity (ANI) analysis, comprehensive annotation of antimicrobial resistance and virulence genes, multilocus sequence typing (MLST), and core-genome SNP (cgSNP)-based phylogenetics. RESULTS: Aeromonas was detected in 3.3% (23/691) of patients, with Aeromonas veronii (56.52%, 13/23) and Aeromonas caviae (26.09%, 6/23) predominating. Co-infections with other enteric pathogens occurred in 65.2% of positive cases. Resistance rates were notably high for ampicillin/ampicillin-sulbactam (78.26%), nalidixic acid (56.52%), and ertapenem (21.73%), and 65.21% of isolates were multidrug-resistant. Genotypic-phenotypic concordance was robust, with β-lactamase genes ampS (60.87%) and blaCEPH-A3 (47.83%) being most prevalent. Strikingly, mcr-3.25 and mcr-3.3, which belong to the mcr family (originally described as mobile colistin resistance genes), were identified in 8.70% of isolates, exhibiting perfect correlation with phenotypic resistance. Plasmer analysis suggested both mcr genes to be chromosomally encoded. Comparative genomic analysis of virulence-associated genes revealed striking species-specific specialization: A. veronii predominantly carried complete T3SS clusters (61.5%), A. caviae and Aeromonas enteropelogenes were enriched in T6SS genes, and a single A. dhakensis isolate possessed an extensive arsenal including T3SS, T6SS, and a full RTX toxin cluster. MLST resolved the 23 isolates into 22 sequence types, 18 of which were novel. Phylogenetic reconstruction identified a tight monophyletic cluster of three A. veronii isolates (9-27 SNP differences) recovered within a 96-h window, suggestive of a potential cluster that warrants further epidemiological investigation. Comparative genomic analysis of the rare species Aeromonas allosaccharophila demonstrated that the Beijing clinical isolate S14 differs from the U.S. clinical strain ATCC 35942 by 42,099 SNPs, confirming its distinct genetic lineage. CONCLUSION: Collectively, this study delineates high genetic diversity, emerging chromosomal colistin resistance, and species-specific virulence specialization among Aeromonas isolates from diarrheal patients in Beijing. The detection of a potential outbreak cluster and a rare clinical isolate underscores the power of genomics-based surveillance for detecting and mitigating foodborne pathogen threats.

Aeromonas↗

PubMed1998

Identification of non-acetylated metallothioneins induced in rat liver by zinc.

In addition to the usual two rat metallothionein (MT) isoforms (MT-I and MT-II), a third isoform of metallothionein (MT-II) is known to be induced by zinc in the liver of rats and mice, and by epidermal growth factors in cultured cells. Although the third isoform has been suggested to be similar and related to MT-II based on its behavior on size-exclusion and ion exchange HPLC columns, further characterization has not been performed. MT-II' was identified in the present study as the unacetylated isoform of MT-II based on mass spectrometric data obtained by matrix assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF MS) (i.e., MT-II' was 42 Da smaller than MT-II in its molecular mass). Chromatographic properties of MT-II' were consistent with this species being an unacetylated isoform of MT-II arising as a result on lack of acetylation rather than a post-translational deacetylation event (i.e., an isoform of MT-II not co-translationally acetylated, based on the change in its composition relative to MT-II and MT-I after induction of MT expression). Although MT-I' was not separated under the present conditions, the MT-I fraction gave a mass peak corresponding to a species 42 Da smaller than MT-I. This suggested that non-acetylated isoforms of both MT-1 and MT-II were present.

Animals↗

PubMedDate not supplied

A chimeric anti-CEA antibody with heavy interchain disulfide bonds deleted: molecular characterization and biodistributions in normal and tumor bearing mice.

We have deleted the interchain disulfide bonds in a chimeric anti-CEA antibody (chT84.66) by mutating two cysteines in the heavy chain to glycine residues. The resulting antibody delta SSchT84.66 was expressed in high yield in a bioreactor and purified to homogeneity in a single step on an anti-idiotypic antibody affinity column. The molecular size of the antibody was 150 kDa as judged by gel filtration, SDS gel electrophoresis under non-reducing conditions, and MALDI-TOF/MS. The 150 kDa antibody had nearly identical kinetic (Kon = 1.53 x 10(6) M-1 s-1, .koff = 1.14 x 10(-5) s-1) and affinity constants (Kaff = 1.34 x 10(11) M-1) compared to the parent murine (Kaff = 1.25 x 10(11) M-1) and chimeric (Kaff = 1.16 x 10(11) M-1) antibodies when tested on biosensor chips. When delta SSchT84.66 was conjugated to the isothiocynato derivative of DTPA, radiolabeled with 111In, and injected into either normal or nude mice bearing tumor xenografts, it gave nearly identical biodistributions to chT84.66. delta SSchT84.66 and chT84.66 antibodies gave a maximum tumor uptake of 48 and 74% ID/g, and tumor to blood ratios of 5.3 and 6.2 at 48 h, respectively. We conclude that delta SSchT84.66 irreversibly associates into H2L2 dimers after concentration, that the dimers are stable under both the in vitro and in vivo conditions used in this study, and the properties of the antibody are virtually indistinguishable from the parent chT84.66 antibody.

Animals↗

PubMed1999

Fluorescence and mass spectrometry studies of meta-tetra(hydroxyphenyl)chlorin photoproducts.

The meta-tetra(hydroxyphenyl)chlorin (m-THPC), a second-generation sensitizer used in photodynamic therapy (PDT), is currently under clinical trial. In vivo fluorometry provides direct evidence that photobleaching processes are induced at the tumor site during PDT. Photoproduct formation has thus to be taken into account to fully understand PDT treatment. A preliminary step is to determine the fluorescence characteristics of photoproducts formed in solution. Solutions of m-THPC irradiated at 514 nm have been separated by HPLC using absorption and fluorescence detection. Six main photoproducts have been isolated. According to matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) results, five fluorescent photoproducts emitting at 652 nm have been attributed to three mono-, one di- and one tri-hydroxy derivatives (m/z 697, 713 and 729, respectively). Fluorescence characteristics of mono-hydroxy forms were found to be similar to those of m-THPC, whereas fluorescence yields in di- and tri-hydroxy derivatives were very low. Another product, corresponding to a MALDI-TOF MS main signal at m/z 542, showed an absorption spectrum maximum at 522 nm while a weak fluorescence was detected at 480 nm. The loss of the Soret band suggests that this photoproduct results from the opening of the reduced pyrrole ring. The part played by each of these products in the photobleaching phenomenon of m-THPC is discussed.

Chromatography, High Pressure Liquid↗

PubMed1999

Stereoselectivity of the phase-II-metabolism of the H1 antihistaminic drug dimethindene investigated by capillary electrophoresis.

Two capillary electrophoretic (CE) methods for the determination of conjugated metabolites of the antihistaminic drug dimethindene were developed. These methods allow the determination of the diastereomeric ratios of both Phase II glucuronides, 6-hydroxy dimethindene glucuronide (5) and 6-hydroxy-N-demethyl dimethindene glucuronide (6). Furthermore, after enzymatic deconjugation of both glucuronides, enantiomeric ratios of the hydroxylated Phase I metabolites 3 and 4 were determined. For comparison, glucuronides 5 and 6 were prepared by enzymatic synthesis and identified by MALDI-TOF mass spectrometry and deconjugation with beta-glucuronidase to the corresponding phenols 3 and 4. The assay of the glucuronides in rat urine and serum was performed by a combination of liquid/liquid extraction followed by solid phase extraction. After a high dose treatment with racemic dimethindene the diastereomeric glucuronides 5 and 6 could be directly determined in the urine of a guinea pig by CE without prior extraction or preconcentration of the urine sample. In all cases, stereoselectivities of the formation of Phase I as well as Phase II metabolites were observed.

Animals↗

PubMed2000

[The degradation of glycoproteins with lithium borohydride. Isolation and analysis of O-glycopeptides with reduced C-terminal amino acid residue].

By the example of fetuin and a blood-group-specific mucin from porcine stomach, we showed that, under conditions of reductive degradation of glycoproteins with LiBH4-LiOH in 70% aqueous tert-butyl alcohol, the reduction and cleavage of amide bonds occur much faster than the simultaneous beta-elimination of carbohydrate chains O-linked with Ser and Thr residues of the peptide chain. The major degradation products containing the O-linked glycans are the O-glycosylated derivatives of 2-aminopropane-1,3-diol and 2-aminobutane-1,3-diol (the products of reduction of glycosylated Ser and Thr) and the glycopeptides containing 2-4 amino acid residues with reduced C-terminal amino acid. Seventeen homogeneous O-glycopeptides were isolated from the fetuin degradation products by ion-exchange and reversed-phase HPLC. Their structures were determined by MALDI-TOF mass spectrometry and by analyses for amino acids, amino alcohols, and carbohydrates. The application of the reaction for characterization of O-glycans and localization of O-glycosylation sites in O- and N,O-glycoproteins is discussed.

Animals↗

PubMed2000

Mass spectrometric analysis of rhodopsin from light damaged rats.

PURPOSE: It is well established that the retina is damaged by intense visible light. Rhodopsin has been proposed to be involved in this process. We therefore undertook to examine whether rhodopsin isolated from light damaged animals is structurally altered at the molecular level. METHODS: Dark reared and dim cyclic light reared 8 week old Sprague-Dawley rats were exposed to intense visible light and sacrificed immediately or 24 h after exposure together with unexposed control animals reared under the same conditions. Rod outer segments were isolated by sucrose gradient ultracentrifugation, their membranes treated with urea, then washed with Tris buffer. The rhodopsin preparations were then reduced, pyridylethylated, delipidated, and cleaved with CNBr. Reversed phase HPLC was used to separate the fragments, and the effluent was analyzed online with a Finnigan LCQ ion trap mass spectrometer. C-terminal phosphorylation was investigated following Asp-N cleavage. MALDI-TOF mass spectrometry was used for the identification of glycosylation. RESULTS: The rat rhodopsin protein was mapped with the exception of two single amino acid fragments. The reported sequence was confirmed with the exception of the controversial T/S320 residue, which was found to be a threonine. Mono-, di-, tri-, and tetraphosphorylated forms of rhodopsin were found in the light damaged animals. Three sites of phosphorylation were confirmed with MS/MS (tandem mass spectral) data. Single or double phosphorylations were found among these three sites, in various combinations. Dark adaptation completely reversed the phosphorylation in all light damaged animals. Other posttranslational modifications were as previously reported. CONCLUSIONS: Our results indicate that intense visible light exposure of rats does not lead to oxidative or other primary structural alterations in the rhodopsin protein of rod outer segments. We also report that the mutated rhodopsin (P23H) is present in rat rod outer segments from heterozygous animals and that residue 320 in both normal and mutated rhodopsins is threonine, not serine.

Amino Acid Sequence↗

PubMed2000

Protein processing mechanisms: from angiotensin-converting enzyme to Alzheimer's disease.

Angiotensin-converting enzyme (ACE) and the Alzheimer's disease amyloid precursor protein are two examples of membrane-bound proteins that are released in a soluble form by a post-translational proteolytic cleavage event involving a secretase. Site-specific antibodies and matrix-assisted laser desorption ionization-time-of-flight ('MALDI-TOF') MS have been used to map the secretase cleavage site in somatic ACE to Arg-1203/Ser-1204, 24 residues proximal to the membrane-anchoring domain. Trypsin, which can solubilize ACE from the membrane, cleaves the protein at the same site. The use of structurally related hydroxamic acid-based zinc metalloproteinase inhibitors indicate that tumour necrosis factor-alpha convertase, a member of the ADAMs ('a disintegrin and metalloproteinase') family of proteins, is not involved in the proteolytic release of ACE, or in the constitutive or regulated alpha-secretase release of the amyloid precursor protein from a human neuronal cell line.

ADAM Proteins↗

PubMed2026

[Genes determining virulence factors of Escherichia coli strains isolated from prostate secretions patients with chronic bacterial prostatitis].

UNLABELLED: The aim of the work is to characterize virulence genes of E. coli strains isolated from prostate secretions patients with chronic bacterial prostatitis. MATERIALS AND METHODS: Escherichia coli were isolated from the prostate secretions of men of reproductive age (20-45 years) with chronic bacterial prostatitis using a generally accepted bacteriological method, the type was determined using MALDI-TOF mass spectrometry, virulence genes were PCR and sequencing. RESULTS: The genomes of the studied strains contain genes encoding groups of virulence factors: adhesins, toxins, capsule antigens, siderophores, invasins, and anti-immunity of the macroorganism. Itwas shown that the genes of adhesins, siderophores, and immune system counteraction factors prevailed in E. coli. CONCLUSION: Further studies of E. coli strains using genome-wide sequencing and proteomics technologies are needed. The accumulation of the obtained data will make it possible to use virulence genes as diagnostic markers in patients with chronic prostatitis, indicating the presence of infection.

Humans↗

PubMedDate not supplied

Mass spectrometric sequencing of synthetic peptides containing alpha, alpha-dialkylated amino acid residues by MALDI post-source decay analysis.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), a method well-suited for mass determination of biomolecules, has been used to analyze fragment ions generated by post-source decay (PSD) of synthetic peptaibols containing high proportions of the sterically hindered amino acids alpha-amino isobutyric acid (Aib) and isovaline (Iva). Since peptaibols do not have a free N-terminal amino group or side chains subject to protonation, the analyzed peptides saturnisporin SA III, trichotoxin A-50 and chrysospermin B were shown to provide preferred N-terminal and C-terminal a, b, and y fragments as sodium adduct. Additionally, a cleavage of the labile Aib-Probond was observed for all peptides investigated. The fragmentation pattern allowed confirmation of the primary structure and, therefore, demonstrated the usefulness of MALDI-PSD mass spectrometry for sequence analysis of the peptaibols.

Alkylation↗

PubMed1996

[Bacterial endotoxins--methods of structural analysis].

The modern structural methods used in the determination of lipopolysaccharides chemical structures were described. The combination of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MALDI-TOF, FAB and EI) applied to structural analysis of lipopolysaccharides, with a few chosen examples of characteristic original spectra were presented.

Bacterial Toxins↗

PubMedDate not supplied

Capillary electrophoresis for purity estimation and in-process testing of recombinant GB virus-C proteins.

Protein purity estimation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with scanning densitometry is a critical component in the manufacture of recombinant proteins for commercial diagnostic assays. However, the procedure is time consuming and often difficult to reproduce because commercial dyes that are used for visualizing proteins do not bind in a stoichiometric fashion for all proteins. The present report describes the use of a rapid and dye-independent SDS polymer-filled capillary gel electrophoresis (CE-SDS) method to estimate protein purity. The CE-SDS method was used for in-process and final purity testing of GB virus-C (GBV-C) fusion proteins produced in E. coli, and was directly compared with the conventional SDS-PAGE method using purified Coomassie blue dye to reduce protein staining anomalies. The CE-SDS method may serve as an alternative or replacement method to the lengthy and tedious SDS-PAGE method. This study also demonstrates that the observed molecular weight of the fusion protein, determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), provides higher accuracy than values estimated by either CE-SDS or SDS-PAGE methods.

Cloning, Molecular↗

PubMed1998

Recent advances in molecular genetics of cardiovascular disorders. Implications for atherosclerosis and diseases of cellular lipid metabolism.

Two developments in molecular genetics will profoundly influence our understanding and the diagnosis of cardiovascular disorders. First, the identification of genes responsible for monogenic and polygenic traits by analysis of e.g. large pedigrees and affected sib pairs provides invaluable data regarding the role of specific genes in common diseases like arteriosclerosis, hypertension, diabetes, thrombosis/hemostasis and obesity. Besides the insights into the underlying pathophysiology, this knowledge will permit to identify persons at high risk for disease development. These patients can then obtain a targeted intervention. The second development is related to the availability of new analytical tools for molecular biology. New methods such as sequencing by hybridisation (SBH), DNA-array technology or matrix assisted laser desorption/ionisation-time of flight mass spectroscopy (MALDI-TOF) permit sequence analysis of complete genes within hours. Automated PCR-technologies with homogenous amplicon detection formats simplify PCR and permit its use in the routine laboratory setting. Considering cardiovascular diseases there is a number of genes involved in lipid metabolism (apolipoproteins, lipoprotein receptors, lipolytic enzymes), thrombosis/hemostasis (platelet receptors, pro- and anticoagulant proteins, fibrinogen, PAI's), hypertension (angiotensin converting enzyme, angiotensinogen) glucose metabolism (glucose transporters, enzymes) and obesity (hormones, receptors), that are interesting candidates for sophisticated genetic risk assessment. Furthermore, there are also gene candidates involved in processes of early atherogenesis and chronic inflammation such as complement proteins, cell adhesion molecules, and cellular receptors and enzymes. Most of these gene candidates were derived from pathophysiologic knowledge and subsequent epidemiological studies. However, it is foreseeable that in the coming years genes will be identified which were not known so far to be involved in cardiovascular diseases. Genetic studies will be of prime importance in this area, as is exemplified by animal models. In the long term, analysis of these candidate genes before the implementation of therapy will permit a targeted intervention approach towards high risk patients. This will reduce the overall costs of health care without reducing the quality.

Arteriosclerosis↗

PubMed1998

Identification of potential diagnostic and vaccine candidates of Helicobacter pylori by "proteome" technologies.

BACKGROUND: There is great interest in characterizing the proteins of the gastric pathogen, Helicobacter pylori, especially those proteins to which humans respond immunologically. Such proteins have potential importance in diagnosis and vaccine development. METHODS: Two-dimensional gel electrophoresis in combination with Western blotting was used to separate and identify potential antigens of Helicobacter pylori strain Z-170. Proteins found to be reactive with pooled sera from 14 infected patients were individually digested in situ with endoproteinase Lys-C, and the resulting fragments were analyzed by matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: Over 20 proteins were reactive in Western blots with pooled sera from 14 infected patients. The mass spectral data was compared with predictions from the H. pylori genome DNA sequence. Each of the 20 proteins was readily identified. CONCLUSIONS: We propose that this "proteome" approach for identification of previously unknown proteins will be useful in examining regulation of H. pylori gene expression and protein localization in the development of improved serologic tests to detect and monitor H. pylori infection. This approach will also be useful for identifying potential targets for antimicrobial or vaccine development for H. pylori and other pathogens whose genomes have been sequenced.

Antigens, Bacterial↗

PubMed1998

Appropriate mammalian expression systems for biopharmaceuticals.

Process development for biopharmaceuticals is dictated by product quality, drug safety and economy of the manufacturing process. Not surprisingly, these factors also play a key role in the evaluation of mammalian cell expression systems to be used in the production of pharmacologically active glycoproteins. To date, the most prominent candidates for efficient expression of glycoproteins are mammalian cell lines such as mouse fibroblast cells (C 127-BPV), Chinese hamster ovary cells (CHO-DHFR, CHO-NEOSPLA, CHO-GS), mouse myeloma cells (NSO-GS) as well as transgenic animals carrying c-DNA or genomic DNA which codes for the protein of interest. The expression titer in the case of glycoproteins is mainly determined by the promoter construct, the site of integration into the chromosome, the copy number and the type of protein in question. Based on expression titer, CHO-NEOSPLA and NSO-GS expression systems are most effective in the production of monoclonal antibodies and, to a lesser extent, of recombinant DNA derived proteins. However, based on overall product yield, expression of recombinant DNA derived proteins in transgenic animals is by far the most promising system. Therefore, for proteins required in large quantities, transgenic expression systems offer an attractive choice. However, cost of goods for products for which the dosage or the overall annual quantities are low, is dominated by downstream processing, filling, lyophilization and packaging and not by the fermentation process. Such proteins are preferentially produced by classical mammalian cell culture systems. Concerns which have to be addressed with respect to drug safety in the transgenic animal approach are the size of the herd, genetic stability from animal to animal, variation in productivity and in impurity profiles during lactation periods, microbial, viral, mycoplasma and prion contaminants, the dependence on health status and the life span of the animal. In a number of cases glycosylation of the protein is relevant for the prevention of immunogenicity of the protein, the pharmacological activity, the pharmacokinetic profile, solubility and stability against proteolysis. The glycosylation pattern, depending on protein structure, is influenced by the enzymatic system of the host cell as well as by fermentation conditions. Therefore, selection of host cells and culture conditions must take into account the requirement for a specific and stable glycosylation pattern. For the assessment of glycovariants, a number of protein analytical methods such as peptide mapping, isoelectric focusing, oligosaccharide mapping, MALDI-TOF (matrix assisted laser desorption mass spectrometry-time of flight), capillary electrophoresis and specific potency assays are available. In our experiments, glycosylation of proteins expressed in CHO cells was demonstrated to be very stable. Only extreme process times, cultivation methods and ammonium ion concentrations had an influence on the glycosylation profile. Among the three products investigated--tissue plasminogen activator (t-PA), interferon omega and soluble intercellular adhesion molecule (s-ICAM)--t-PA expressed the most stable glycosylation pattern. Only at extreme ammonium concentrations an increase of mannose-5 structures was observed, whereas biantennary complex structures were reduced. On the other hand, interferon omega and s-ICAM showed greater susceptibility to increased ammonium concentrations and to adherent cultivation. Such conditions induced quantitative changes to the glycosylation pattern favoring the appearance of higher branched structures. Short cultivation times resulted in more heterogenous oligosaccharide structures. Since the glycosylation of the three proteins is different in the same host cell, the amino acid sequence of the protein apparently influences the glycosylation pattern and its sensitivity to culture conditions. In NSO-mouse myeloma cells, production of s-ICAM is two times as high as in CHO cells

Animals↗

PubMed2026

Burkholderia arboris bacteremia initially identified as Burkholderia cepacia complex: a genome-based case report.

We report a bloodstream Burkholderia arboris isolate from a 75-year-old man without cystic fibrosis. The organism was recovered from both aerobic bottles of two separately collected blood-culture sets and was initially assigned to the Burkholderia cepacia complex (Bcc) by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Whole-genome sequencing yielded three circular chromosomes and one circular plasmid. DFAST_QC identified B. arboris as the only type-strain match above the species threshold, with an average nucleotide identity of 99.48%; the next-highest match was B. seminalis at 93.33%. Multilocus sequence typing identified ST-2575, and ResFinder detected no acquired antimicrobial resistance genes. The patient improved after 14 days of meropenem therapy without recurrent B. arboris bacteremia. This report adds a clinically supported bloodstream infection, a complete genome resource, and detailed susceptibility data, while illustrating the importance of up-to-date reference genomes for species-level interpretation of unusual Bcc isolates.

Humans↗

PubMed2026

Development and validation of a serum peptidomic signature for early detection of asymptomatic ovarian cancer: A multi-center prospective study.

Early detection of asymptomatic ovarian cancer (asym-OC) remains a critical challenge, the failure of which underlies its high mortality. Performing serum peptidomic profiling of 843 participants in the cohort SOCFCP, we distill 1,081 initial features into a 7-marker panel for asym-OC detection via a biology-informed machine-learning (ML)-based feature selection strategy. Three markers significantly revert toward non-OC levels after surgery. Integrating the panel with age, CA125, and HE4, we develop and externally validate (n = 159) a LightGBM model, ProMS+. For early-stage OC detection, ProMS+ shows a specificity of 92.6% at 95.0% sensitivity, outperforming CA125 (44.7%), HE4 (11.2%), and Risk of Ovarian Malignancy Algorithm (ROMA) (24.0%), with an area under the curve (AUC) of 0.993. In a simulated high-risk population (n = 100,000; OC prevalence = 1%), ProMS+ yields a high AUC (0.983) and a higher positive predictive value than CA125, HE4, and Age + CA125 + HE4 combined model (0.201 vs. 0.027, 0.090, and 0.064). ProMS+ offers a promising, non-invasive, and interpretable approach for the early detection of asym-OC.

Humans↗