Cross-Catalysis between Self-Replicators of Different Handedness

Life, as we know it today, requires the homochirality of its constituents. Yet it is likely that the prebiotic soup was a racemic mixture of molecules. It remains an open question at which point in evolution homochirality became necessary for life. Self-replicating molecules are expected to be a possible link between inanimate and animate matter. We here report the interplay between chirality and self-replication, and specifically investigated cross-catalysis between replicating species containing building blocks of different handedness. We find that, although replication of species from the same handedness is more efficient in isolated systems, nonstereoselective cross-catalysis dominates and leads to the formation of heterochiral self-replicators when a racemic mixture of building blocks is provided. These results demonstrate that homochirality is not a prerequisite for self-replication, and that chiral symmetry breaking could have occurred after the emergence of self-replicating systems from racemic mixtures

Sensitive, homogeneous, and label-free protein-probe assay for antibody aggregation and thermal stability studies

Protein aggregation is a spontaneous process affected by multiple external and internal properties, such as buffer composition and storage temperature. Aggregation of protein-based drugs can endanger patient safety due, for example, to increased immunogenicity. Aggregation can also inactivate protein drugs and prevent target engagement, and thus regulatory requirements are strict regarding drug stability monitoring during manufacturing and storage. Many of the current technologies for aggregation monitoring are time- and material-consuming and require specific instruments and expertise. These types of assays are not only expensive, but also unsuitable for larger sample panels. Here we report a label-free time-resolved luminescence-based method using an external Eu3+-conjugated probe for the simple and fast detection of protein stability and aggregation. We focused on monitoring the properties of IgG, which is a common format for biological drugs. The Protein-Probe assay enables IgG aggregation detection with a simple single-well mix-and-measure assay performed at room temperature. Further information can be obtained in a thermal ramping, where IgG thermal stability is monitored. We showed that with the Protein-Probe, trastuzumab aggregation was detected already after 18 hours of storage at 60 degrees C, 4 to 8 days earlier compared to SYPRO Orange- and UV250-based assays, respectively. The ultra-high sensitivity of less than 0.1% IgG aggregates enables the Protein-Probe to reduce assay time and material consumption compared to existing techniques

Protease substrate‐independent universal assay for monitoring digestion of native unmodified proteins

Proteases are a group of enzymes with a catalytic function to hydrolyze peptide bonds of proteins. Proteases regulate the activity, signaling mechanism, fate, and localization of many proteins, and their dysregulation is associated with various pathological conditions. Proteases have been identified as biomarkers and potential therapeutic targets for multiple diseases, such as acquired immunodeficiency syndrome, cardiovascular diseases, osteoporosis, type 2 diabetes, and cancer, where they are essential to disease progression. Thus, protease inhibitors and inhibitor-like molecules are interesting drug candidates. To study proteases and their substrates and inhibitors, simple, rapid, and sensitive protease activity assays are needed. Existing fluorescence-based assays enable protease monitoring in a high-throughput compatible microtiter plate format, but the methods often rely on either molecular labeling or synthetic protease targets that only mimic the hydrolysis site of the true target proteins. Here, we present a homogenous, label-free, and time-resolved luminescence utilizing the protein-probe method to assay proteases with native and denatured substrates at nanomolar sensitivity. The developed protein-probe method is not restricted to any single protein or protein target class, enabling digestion and substrate fragmentation studies with the natural unmodified substrate proteins. The versatility of the assay for studying protease targets was shown by monitoring the digestion of a substrate panel with different proteases. These results indicate that the protein-probe method not only monitors the protease activity and inhibition, but also studies the substrate specificity of individual proteases.</p

The survival rate of hepatocellular carcinoma in Asian countries

Hepatocellular carcinoma or Liver cancer (LC) is the sixth most common cancer and the fourth cause of death worldwide in 2018. There has not been a comprehensive study on the survival rate of patients with LC in Asia yet. Therefore, the present study was conducted to evaluate the survival rate of patients with LC in Asian countries. The methodology of the present study is based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The researchers searched five international databases including Medline/PubMed, Scopus, Embase, Web of Knowledge and ProQuest until July 1, 2018. We also searched Google Scholar for detecting grey literature. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of selected papers. A total of 1425 titles were retrieved. 63 studies met the inclusion criteria. Based on the random-effect model one-year, three-year and five-year survival rate of LC were 34.8 % (95 % CI; 30.3-39.3), 19 % (95 % CI ; 18.2-21.8) and 18.1 % (95 % CI ;16.1-20.1) respectively. According to the results of our study, the LC survival rate in Asian countries is relatively lower than in Europe and North America

Efficient and highly selective oxidation of primary and secondary alcohols by butyltriphenylphosphonium chlorochromate under non-aqueous conditions

195-198Butyltriphenylphosphonium chlorochromate 1 (BTPPCC) is used as a new and selective reagent for the oxidation of benzylic and allylic alcohols to the corresponding carbonyl compounds in refluxing acetonitrile

Article Oligonucleotide-Peptide Conjugates: Solid-Phase Synthesis under Acidic Conditions and Use in ELISA Assays

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Cross-Catalysis between Self-Replicators of Different Handedness

Life, as we know it today, requires the homochirality of its constituents. Yet it is likely that the prebiotic soup was a racemic mixture of molecules. It remains an open question at which point in evolution homochirality became necessary for life. Self-replicating molecules are expected to be a possible link between inanimate and animate matter. We here report the interplay between chirality and self-replication, and specifically investigated cross-catalysis between replicating species containing building blocks of different handedness. We find that, although replication of species from the same handedness is more efficient in isolated systems, nonstereoselective cross-catalysis dominates and leads to the formation of heterochiral self-replicators when a racemic mixture of building blocks is provided. These results demonstrate that homochirality is not a prerequisite for self-replication, and that chiral symmetry breaking could have occurred after the emergence of self-replicating systems from racemic mixtures

The Use of Chimeric Vimentin Citrullinated Peptides for the Diagnosis of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.This work has been partially funded by Grant FIS PI080207 from the Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain.Peer reviewe