Comparative Analytical Evaluation of the Proposed Biosimilar FYB206 and its Reference Medicinal Product Keytruda.

Background And Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials.

Picomolar inhibition of SARS-CoV-2 variants of concern by an engineered ACE2-IgG4-Fc fusion protein.

SARS-CoV-2 enters host cells after binding through its spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor. Soluble ACE2 ectodomains bind and neutralize the virus, yet their short in vivo half-live limits their therapeutic use. This limitation can be overcome by fusing the fragment crystallizable (Fc) part of human immunoglobulin G (IgG) to the ACE2 ectodomain, but this bears the risk of Fc-receptor activation and antibody-dependent cellular cytotoxicity.

N-glycans of complex glycosylated biopharmaceuticals and their impact on protein clearance.

N-glycosylation is a common post-translational modification of biopharmaceutical products. Certain types of N-glycans have been shown to influence important properties of monoclonal antibody products including pharmacokinetics and effector functions. Complex biopharmaceuticals e.

The genomes of two key bumblebee species with primitive eusocial organization.

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species.

A mass spectrometry-based approach to host cell protein identification and its application in a comparability exercise.

Host cell proteins (HCPs) are process-related impurities present in biopharmaceuticals and are generally considered to be critical quality attributes. Changes in a biopharmaceutical production process may result in qualitative shifts in the HCP population. These shifts are not necessarily detectable when overall HCP levels are measured with traditional approaches such as enzyme-linked immunosorbent assays (ELISAs).

The role of methylation of DNA in environmental adaptation.

Methylation of DNA is an epigenetic mechanism that influences patterns of gene expression. DNA methylation marks contribute to adaptive phenotypic variation but are erased during development. The role of DNA methylation in adaptive evolution is therefore unclear.

Reversible switching between epigenetic states in honeybee behavioral subcastes.

In honeybee societies, distinct caste phenotypes are created from the same genotype, suggesting a role for epigenetics in deriving these behaviorally different phenotypes. We found no differences in DNA methylation between irreversible worker and queen castes, but substantial differences between nurses and forager subcastes. Reverting foragers back to nurses reestablished methylation levels for a majority of genes and provides, to the best of our knowledge, the first evidence in any organism of reversible epigenetic changes associated with behavior.

Genome-wide association between DNA methylation and alternative splicing in an invertebrate.

Background: Gene bodies are the most evolutionarily conserved targets of DNA methylation in eukaryotes. However, the regulatory functions of gene body DNA methylation remain largely unknown. DNA methylation in insects appears to be primarily confined to exons.

Age-related learning deficits can be reversible in honeybees Apis mellifera.

Many animals are characterized by declining brain function at advanced ages, including honeybees (Apis mellifera). Variation in honeybee social development, moreover, results in individual differences in the progression of aging that may be accelerated, delayed, and sometimes reversed by changes in behavior. Here, we combine manipulations of social development with a measurement of sensory sensitivity, Pavlovian (associative) learning, and a proteomic technique to study the brain of aged honeybees.

A vitellogenin polyserine cleavage site: highly disordered conformation protected from proteolysis by phosphorylation.

Vitellogenin (Vg) is an egg-yolk precursor protein in most oviparous species. In honeybee (Apis mellifera), the protein (AmVg) also affects social behavior and life-span plasticity. Despite its manifold functions, the AmVg molecule remains poorly understood.

IRS and TOR nutrient-signaling pathways act via juvenile hormone to influence honey bee caste fate.

Regardless of genetic makeup, a female honey bee becomes a queen or worker depending on the food she receives as a larva. For decades, it has been known that nutrition and juvenile hormone (JH) signaling determine the caste fate of the individual bee. However, it is still largely unclear how these factors are connected.

The worker honeybee fat body proteome is extensively remodeled preceding a major life-history transition.

Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition.

Draft genome of the red harvester ant Pogonomyrmex barbatus.

We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing.

Insulin receptor substrate influences female caste development in honeybees.

The insulin/insulin-like signalling (IIS) network is conserved among animals and is central to growth and development. In eusocial honeybees (Apis mellifera), IIS is hypothesized to shape female caste fate. We tested this hypothesis via RNA interference (RNAi) knockdown of the insulin receptor substrate (IRS) homologue, a key adaptor protein in IIS.

Differential gene expression and protein abundance evince ontogenetic bias toward castes in a primitively eusocial wasp.

Polistes paper wasps are models for understanding conditions that may have characterized the origin of worker and queen castes and, therefore, the origin of paper wasp sociality. Polistes is "primitively eusocial" by virtue of having context-dependent caste determination and no morphological differences between castes. Even so, Polistes colonies have a temporal pattern in which most female larvae reared by the foundress become workers, and most reared by workers become future-reproductive gynes.

Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.

We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis.

Deciphering proteomic signatures of early diapause in Nasonia.

Insect diapause is an alternative life-history strategy used to increase longevity and survival in harsh environmental conditions. Even though some aspects of diapause are well investigated, broader scale studies that elucidate the global metabolic adjustments required for this remarkable trait, are rare. In order to better understand the metabolic changes during early insect diapause, we used a shotgun proteomics approach on early diapausing and non-diapausing larvae of the recently sequenced hymenopteran model organism Nasonia vitripennis.

Integration of metabolomic and proteomic phenotypes: analysis of data covariance dissects starch and RFO metabolism from low and high temperature compensation response in Arabidopsis thaliana.

Statistical mining and integration of complex molecular data including metabolites, proteins, and transcripts is one of the critical goals of systems biology (Ideker, T., Galitski, T., and Hood, L.

Plasticity and robustness of protein patterns during reversible development in the honey bee (Apis mellifera).

With age, worker honey bees normally proceed from performing activities inside the nest to foraging in the field, creating an age-related division of labor. We previously established that the whole-body protein profiles of nest workers and foragers are different, and proposed that this proteomic divergence in part is explained by a shift in metabolic requirements as worker bees initiate intense flight. The unique plasticity of honey bee worker ontogeny, however, provides further opportunities to investigate if such changes in the proteome are dynamic or, alternatively, are permanently induced.

A diapause pathway underlies the gyne phenotype in Polistes wasps, revealing an evolutionary route to caste-containing insect societies.

Colonies of social wasps, ants, and bees are characterized by the production of two phenotypes of female offspring, workers that remain at their natal nest and nonworkers that are potential colony reproductives of the next generation. The phenotype difference includes morphology and is fixed during larval development in ants, honey bees, and some social wasps, all of which represent an advanced state of sociality. Paper wasps (Polistes) lack morphological castes and are thought to more closely resemble an ancestral state of sociality wherein the phenotype difference between workers and nonworkers is established only during adult life.

Comparative proteomics reveal characteristics of life-history transitions in a social insect.

Background: Honey bee (Apis mellifera) workers are characterized by complex social behavior. Their life-history is dominated by a period of within-nest activity followed by a phase of long-distance flights and foraging. General insights into insect metabolism imply that foraging onset is associated with fundamental metabolic changes, and theory on social evolution suggests metabolic adaptations that are advantageous for the colony as a whole.

Neutral loss-based phosphopeptide recognition: a collection of caveats.

The standard strategy for analysis by tandem mass spectrometry of protein phosphorylation at serine or threonine utilizes the neutral loss of H3PO4 (= 97.977/z) from proteolytic peptide molecular ions as marker fragmentation. Manual control of automatically performed neutral loss-based phosphopeptide identifications is strongly recommended, since these data may contain false-positive results.

Plant protein phosphorylation monitored by capillary liquid chromatography--element mass spectrometry.

Many essential cellular functions such as growth rate, motility, and metabolic activity are linked to reversible protein phosphorylation, since they are controlled by signaling cascades based mainly on phosphorylation/dephosphorylation events. Quantification of global or site-specific protein phosphorylation is not straightforward with standard proteomic techniques. The coupling of capillary liquid chromatography (microLC) with ICP-MS (inductively coupled plasma-mass spectrometry) is a method which allows a quantitative screening of protein extracts for their phosphorus and sulfur content, and thus provides access to the protein phosphorylation degree.

Integrative profiling of metabolites and proteins: improving pattern recognition and biomarker selection for systems level approaches.

Methods such as mRNA expression profiling have provided a vast amount of genomic and transcriptomic information about plants and other organisms. However, there is explicit indication that considerable metabolic control is executed on the metabolite and on the protein level including protein modifications, thereby constituting the phenotypic plasticity. Consequently, the analysis of the molecular phenotype demands the step toward mass spectrometry (MS)-based postgenomic techniques such as metabolomics and proteomics.