ProterixBio (United States)

Biodiversity genomics is converging from historically separate approaches — DNA barcoding and reference genome sequencing — into an integrated digital ecosystem driven by shared data stewardship principles: transparent provenance, persistent identifiers and interoperable repositories. We demonstrate how these workflows can operate within a unified informatics architecture spanning data generation, validation, publication and reuse. We describe coordinated infrastructure, including the European BOLD mirror, ERGA Genome Tracking Console and metadata platforms COPO and PlutoF. These systems employ harmonised validation pipelines, shared metadata standards that bridge the Darwin Core and Genomic Standards Consortium vocabularies and automated data exchange amongst ENA, UNITE and GBIF. Workflows in Galaxy, Nextflow and Snakemake are registered in WorkflowHub as Research Object Crates (RO-Crates), ensuring reproducibility and complete provenance. Key outcomes include comprehensive data flow documentation, automated quality control using BUSCO and ERGA Assembly Reports and robust specimen-to-data linkage. We identify challenges in metadata harmonisation, distributed tracking, collaborative attribution and infrastructure sustainability and provide recommendations for addressing them through existing platforms and emerging RO-Crate standards. This work establishes practical foundations for treating biodiversity molecular data as a continuum, demonstrating how FAIR principles can scale to continental initiatives.

Sex cord-like morphology is now a well-known feature of occasional examples of endometrioid carcinoma of the ovary or fallopian tube. Recently, we have observed that these tumors are frequently negative for PAX8, prompting us to review their morphologic, immunohistochemical, and genomic spectrum. Twenty tumors (17 ovarian, 3 fallopian tube) with available tissue were identified in patients ranging from 32 to 78 (median 60) years. Sex cord-like patterns included cords/trabeculae (n=17), small tubular glands (n=16), and "granulosa-like" nests (n=12). In addition, 1 had ependymoma-like features with perivascular pseudorosettes and 3 had focal spindled cells. Conventional endometrioid glands were often sparse. All had conspicuous fibromatous stroma and 11 tumors had background endometrioid adenofibromas. Six tumors had associated endometriosis. PAX8 was positive in only 2/20 (diffuse in both), while SOX17 was positive in all (focal in 1, diffuse in 19). Beta-catenin showed aberrant nuclear staining in 17/20. Of the 10 sequenced tumors, 9 showed activating pathogenic variants in CTNNB1; each of these also showed nuclear beta-catenin staining. All lacked alterations in mismatch repair genes, TP53 , and POLE . In summary, adnexal endometrioid carcinomas with sex cord-like features are frequently PAX8-negative, which may result in diagnostic difficulty. However, SOX17 is typically positive and thus useful to establish the diagnosis. Most of these tumors are classified in the "no specific molecular profile" subgroup and have high rates of nuclear beta-catenin/ CTNNB1 alterations. Awareness of these morphologic and immunohistochemical associations may help avoid misclassification as sex cord-stromal or other neoplasms.

WRN helicase is an established synthetic lethal target for inhibition in the treatment of microsatellite instability-high (MSI-H) and mismatch repair deficient (MMRd) cancers. The identification of helicase inhibitors is challenging as high-throughput biochemical screening campaigns typically return few validated hits that are often inactive in cell-based assays. Herein, we highlight the power of non-covalent fragment-based lead discovery in locating new druggable allosteric sites on WRN, enabling us to bypass the challenging behavior of WRN during high-throughput screening hampering hit identification. During the fragment optimization process, structures of WRN with key prioritized fragments reveal multiple conformations of WRN with significant domain rotations up to 180°, including a WRN conformation not previously described. Rooted in a combination of biochemical, biophysical, and structural approaches, we present the detailed analyses of optimized chemical matter evolved from screening hits and the unique ability of WRN to accommodate diverse conformations as detailed by structural characterization.

Abstract This study focused on the development of functional dairy products fortified with bioactive peptides derived from Lactobacillus rhamnosus C25–fermented sheep milk and their evaluation during storage. Microencapsulated peptides were incorporated into flavoured milk and srikhand, and their antimicrobial, antioxidant, and sensory properties were monitored over refrigerated storage. Flavoured milk supplemented with free peptides exhibited strong antimicrobial activity, while encapsulated peptides provided a controlled and sustained release, maintaining functionality over six days. In srikhand, both plain and mango-flavoured formulations demonstrated enhanced biofunctional properties, with encapsulated peptides showing gradual peptide release, higher antioxidant activity, and better preservation of sensory quality over 15 days. Sheep milk used for fermentation showed good microbial quality, supporting safe peptide production. Fermentation yielded peptide fractions (<3, <5, and <10 kDa), which were analyzed using RP-HPLC and LC-MS/MS, identifying over 3,100 peptides. In silico screening predicted 34 peptides with antimicrobial potential, including cationic and amphipathic α-helical peptides primarily derived from β-casein and κ-casein. Functional assays demonstrated potent antimicrobial activity against Gram-positive and Gram-negative pathogens, particularly in the 5–10 kDa fractions. Antioxidant activity was highest in the 5 kDa retentate, indicating that medium-sized peptides contributed most to radical scavenging. Microencapsulation using sodium alginate improved peptide stability and controlled release, mitigating bitterness and preserving product acceptability. Overall, the study highlights the potential of L. rhamnosus C25–fermented sheep milk peptides as natural bioactive ingredients for functional dairy products with enhanced shelf life, antimicrobial efficacy, and antioxidant capacity. Graphical abstract

Meiotic failure is a major cause of infertility, but the lack of an in vitro model of human meiosis is a barrier to understanding its mechanism. Here, we establish a method to initiate meiosis directly from male or female human-induced pluripotent stem cells (iPSCs). DNMT1 inhibition, retinoid signaling activation, and overexpression of regulatory factors (antiapoptotic BCL2 and promeiotic HOXB5, BOLL, or MEIOC) rapidly activates meiosis over a 15-day protocol. Our protocol bypasses the primordial germ cell stage and directly generates cells expressing genes similar to meiotic oogonia, including oogonia markers, all synaptonemal complex components, and meiotic recombination machinery. DNMT1 inhibition rapidly erases DNA methylation, including at imprinting control regions and promoters of meiotic genes. Microscopy shows key aspects of meiosis, including chromosome axis formation and synapsis in live human cells. Our model of human meiosis provides opportunities for studying this critical reproductive process under chemically defined conditions in vitro.

ABSTRACTIntroductionExcitatory/inhibitory (E/I) imbalance is a proposed neural disruption in schizophrenia supported by magnetic resonance spectroscopic imaging (MRSI) evidence of altered gamma‐aminobutyric acid (GABA) and glutamate (Glu) levels. However, there exists a paucity of data linking these abnormalities to impaired in vivo brain function putatively reflecting E/I imbalance. Here, associations between GABA/Glu and the evoked early auditory gamma‐band response (EAGBR) were examined in first‐episode schizophrenia (FESz).MethodsTwelve FESz underwent resting‐state 7T‐MRSI and magnetoencephalography (MEG) recorded during an auditory oddball task. MRSI spectra and source‐localized MEG data were extracted from overlapping regions of left (LH) and right (RH) superior temporal sulcus. Associations between evoked EAGBR power and GABA/Glu, GABA/Cre, and Glu/Cre ratios were assessed. The Brief Psychiatric Rating Scale (BPRS) and Global Functioning: Role/Social (GF: Role/Social) scales were collected.ResultsGABA/Glu ratios were inversely correlated with EAGBR power (LH: ρ = −0.87; RH: ρ = −0.85). LH GABA/Glu ratios were also inversely correlated with BPRS scores (ρ = −0.64) and positively correlated with GF: Social (ρ = 0.64) scores while RH EAGBR power was positively correlated with BPRS scores (ρ = 0.70). Stepwise linear regressions suggest these relationships were driven primarily by GABA concentrations.ConclusionAssociations in FESz between GABA/Glu ratios, clinical ratings, and EAGBR power suggests this evoked gamma‐band response reflects cortical hyperexcitability within the auditory system that is closely tied to disease debility at this early illness stage. These data highlight the potential of merging high‐precision, in vivo neuro‐chemical assays via 7‐Tesla MRSI and physiological measures from MEG to validate established cellular models of disease.

Humans have both negative and positive impacts on marine communities: human everyday activities can degrade ecosystems, while conservation efforts can support their protection and recovery. Using an empirical database of fish assemblages compiled from 393 underwater visual censuses along the Colombian Pacific Coast, we assessed spatial variation in these assemblages and investigated whether they are shaped by human pressures, such as number of fishers and proximity to markets, as well as conservation measures, including protection status and the age of the marine protected areas. Our study reveals that remote locations have a higher fish density and biomass than those near the coast. We found that grunts (Haemulidae) were the most species-rich family and contributed the most to fish density and biomass. Piscivores were the trophic group most affected by human factors, showing lower species richness, density, and biomass in coastal locations. In contrast, other trophic groups did not show a negative response to human factors across locations. We did not observe an effect of human and conservation factors on the total species richness. To evaluate the potential influence of Malpelo island, the only oceanic location in the dataset, we built two models, one with and one without this site. The results were consistent across both models, indicating that including or excluding Malpelo did not alter overall patterns of species richness. However, market distance negatively influenced the average fish density and biomass when all locations were included. Our results provide the first quantitative assessment of fish assemblages across the Colombian Pacific Coast, enabling future comparison and enhancing our understanding of the effects of human and conservation activities on the patterns of species richness, density, and biomass of reef fishes in the Eastern Tropical Pacific.

Genomic sequences that form three-stranded triplexes (TPXs) under physiological conditions (called T-flipons) play an important role in defining DNA nucleosome-free regions (NFRs). Within these NFRs, other flipon types can cycle conformations to actuate gene expression. The transcripts read from the NFR form condensates that engage proteins and small RNAs. The helicases bound then trigger RNA polymerase release by dissociating the 7SK ribonucleoprotein. The TPXs formed usually incorporate RNA as the third strand. TPXs made only from DNA arise mostly during DNA replication. Many small RNA types (sRNAs) and long noncoding (lncRNA) can direct TPX formation. TPXs made with circular RNAs have greater stability and specificity than those formed with linear RNAs. LncRNAs can affect local gene expression through TPX formation and transcriptional interference. The condensates seeded by lncRNAs are updated by feedback loops involving proteins and noncoding RNAs from the genes they regulate. Some lncRNAs also target distant loci in a sequence-specific manner. Overall, lncRNAs can rapidly evolve by adding or subtracting sequence motifs that modify the condensates they nucleate. LncRNAs show less sequence conservation than protein-coding sequences. TPXs formed by lncRNAs and sRNAs help place nucleosomes to restrict endogenous retroelement (ERE) expression. The silencing of EREs starts early in embryogenesis and is essential for bootstrapping development. Once the system is set, EREs play a different role, with a notable enrichment of Short Interspersed Nuclear Repeats (SINEs) in Enhancer-Promoter condensates. The highly programmable TPX-dependent processes create a chromaverse capable of many complexities.

Abstract Background: Evaluation of HER2 status in tissue biopsies, through immunohistochemistry (IHC) and, in equivocal cases, fluorescence in-situ hybridization (FISH), is routinely performed to guide diagnosis and treatment decisions for breast cancer (BC) patients. Tissue biopsy is an invasive procedure for which re-examination is difficult and not commonly performed. Conversely, liquid biopsy is minimally invasive, with unbounded opportunity for recurrent sample collection, allowing monitoring of circulating tumor cells (CTCs). This study aimed to validate a Research Use Only assay by which HER2 immunofluorescence (IF) and FISH are performed on the same CTCs in each sample. Method: Analytical performance of the test was established using contrived samples consisting of HER2+ (SKBR3) and HER2- (MCF-7 and Hs 578T) cultured cancer cells spiked into healthy volunteer blood samples, drawn in Streck Cell-Free DNA tubes. Blood was separated within 144 hours post-draw on ANGLE’s Parsortix® instrument, a marker-independent microfluidic device which isolates CTCs based on size and deformability. Harvests were spun onto CellKeep™ slides and stained with ANGLE’s HER2 IF panel, comprising a nuclear dye, epithelial, mesenchymal and leukocyte markers and an anti-HER2 antibody. Slides were imaged on a BioView Allegro Plus, a platform equipped with artificial intelligence for automated fluorescence imaging, quantitative cellular measurements, CTC candidate identification and reporting. IF stained slides were destained and probed for ERBB2 and CEP17 genes by FISH. Using the Allegro Plus single cell relocation capabilities, CTCs identified by IF were relocated and imaged at 40× to capture HER2 and CEP17 foci. Results. The workflow was performed on a total of 186 contrived samples to determine analytical performance of the assay. Linearity, specificity, sensitivity, repeatability, reproducibility (inter-donor, operators, days and reagents) and endogenous interference (Albumin, Haematocrit and Triglycerides) were assessed. The IF assay was observed to be linear over the range of 0 - 1000 cells, with R2 of 0.96 and degree of non-linearity of 0.004. Analytical specificity and sensitivity of all IF markers were >96%. Analytical specificity and sensitivity of the FISH assay were 100%. The assay was shown to be repeatable and reproducible across spiked donors, operators, days and reagents. Endogenous substances investigated did not affect qualitative results of the assay. Conclusion: This study demonstrated that ANGLE’s combined IF and FISH assay is a robust method for determination of HER2 protein expression and concomitant interrogation of HER2 gene amplification on the cancer cells. This workflow will be utilized to analyze CTCs isolated from a cohort of ∼100 metastatic BC patients to evaluate its clinical feasibility and validity and these results will be reported at the AACR annual meeting. Citation Format: Mariacristina Ciccioli, Alex Young, Laila Vlietinck, Bethan Edwards, Chassidy Johnson, Anne-Sophie Pailhes-Jimenez. Analytical validation of ANGLE's combined IF and FISH assay for assessment of HER2 in circulating tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1981.