Biology subjects

Kowalski, K.

Publications and source records attributed to Kowalski, K..

8 recordsLinked to original sources

bioRxiv2026

Comparative genomics reveals potential mechanisms of invasion in Phragmites australis (common reed)

Biological invasions are transforming ecosystems worldwide, yet the genomic bases enabling certain species to dominate new environments remain poorly understood. Phragmites australis, a widespread wetland grass with invasive and native subspecies co-occurring in North America, provides a powerful system to investigate genomic mechanisms of invasiveness. We generated independent chromosome-scale genome assemblies for invasive P. australis ssp. australis and co-occurring native ssp. americanus and used comparative genomic and transcriptomic analyses to identify lineage-specific innovations associated with invasive success. The invasive subspecies exhibits genomic novelties through functionally-biased single-copy orthologs, intronless genes, and subgenome expression asymmetry, along with a stress-ready basal transcriptome relative to the native subspecies. Following the removal of aboveground shoots ("cutback"), which measures the ability to recover from damage, the invasive subspecies undergoes stronger transcriptional reprogramming, increased shoot production, and higher biomass accumulation compared to the native. It also displays expansion of gene families and coordinately expressed gene modules that support resource mobilization, growth responses to light, and stress tolerance. Beyond Phragmites, comparative analyses across multiple grass genomes, including eight invasive species with related non-invasive species, revealed repeated expansion of gene families associated with abiotic stress tolerance and developmental regulation, suggesting convergent adaptive strategies in the grass family for invasive success. Together, these results demonstrate genomic architecture linked to invasion success and highlight potential targets for managing invasive grasses.

Plant Biology↗

bioRxiv2026

Diabetes Might Shape Vasculature, Tumor Dissemination and Circulating Inflammation Marker Profiles in Prostate Cancer.

Background and objectiveChronic comorbidities like diabetes mellitus can influence cancer incidence and progression. However, their impact on pathological and molecular tumor characteristics, and dissemination, especially in prostate cancer (PCa), is not fully understood. Here, we investigated differences in the PCa molecular landscape with coexisting diabetes type 2 and its link to tumor dissemination. MethodsDAmico intermediate- or high-risk PCa patients (n=145), with type 2 diabetes or no diabetes, were analyzed for clinico-pathological features, circulating tumor cell (CTC) presence, yields and phenotypes in tumor-draining vein (TDVB) and peripheral blood (PB), primary tumor characteristics, and selected plasma biomarkers. Key findings and limitationsDiabetes type 2 was found in 20/13.8% patients and associated with more advanced clinical outcomes, i.e. pathological tumor stage (p=0.011) and lymph node involvement (p=0.020). Among patients diagnosed before age 65, diabetes and PCa showed a borderline association with shorter time-to-biochemical recurrence (p=0.032). Diabetic PCa patients had significantly higher total CTC counts in TDVB but not in PB, indicating enhanced tumor cell dissemination from primary tumor (PT). PTs from diabetic PCa patients displayed a borderline association with higher ALDH1 expression (p=0.054) and significantly lower vascular vessel density (p=0.008). Similarly, in patients under 65, PTs from diabetic PCa patients expressed genes linked to decreased angiogenesis. Plasma analyses revealed elevated GDF15 levels in PB (p<0.001), increased TRAP5 concentrations in TDVB (p=0.001), and reduced osteonectin levels in TDVB (p=0.026) in diabetic PCa patients. The studys limitation is the relatively small cohort, especially those with coexisting diabetes type 2. Conclusion and clinical implicationsDiabetes in PCa patients associates with advanced tumor stage, enhanced tumor cell dissemination, impaired vascularization, and distinct circulating biomarker alterations. Vascular alterations from diabetes, with systemic factors, especially in PCa patients under 65, may increase tumor dissemination in PCa. However, exact mechanisms need investigation in larger cohorts of patients. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/720986v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@1f5047forg.highwire.dtl.DTLVardef@fa3f43org.highwire.dtl.DTLVardef@14f7765org.highwire.dtl.DTLVardef@27a12d_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

CHIP, VCP, and Nucleolar Gatekeepers Remodel the Nucleolus into a Stress-Responsive Proteostasis Hub

The nucleolus, classically dedicated to ribosome biogenesis, also acts as a stress-responsive proteostasis hub. During heat shock, misfolded proteins accumulate in its granular component (GC), but whether this is passive or regulated has been unclear. We show that the ubiquitin ligase CHIP remodels the nucleolus into a reversible protein quality control (PQC) compartment by diverting HSP70 from refolding toward sequestration and transiently suppressing rRNA synthesis. This process requires the segregase VCP, which mediates ubiquitinated substrate flux and couples nucleolar PQC with nuclear and ER stress responses. Functional genomics identify NOL6 and WDR55 as intrinsic gatekeepers with opposing effects on sequestration. We further define three structural states - free-flow, peripheral, and sealed - that encode PQC capacity and recovery potential. Thus, nucleolar proteostasis is revealed as an actively regulated continuum, linking chaperones, ubiquitination, and ribosome biogenesis with global stress adaptation. HighlightsO_LICHIP remodels the nucleolus into a reversible protein quality control (PQC) compartment during heat stress C_LIO_LIVCP drives flux of ubiquitinated substrates and prevents premature resumption of rRNA synthesis C_LIO_LINOL6 promotes, while WDR55 restricts, nucleolar storage of misfolded proteins C_LIO_LIDistinct nucleolar morphologies (free-flow, peripheral, sealed) encode PQC states C_LIO_LIUbiquitination and deubiquitination act as switchable signals, not passive damage marks C_LIO_LINucleolar PQC is integrated with ISR, ER stress, and stress granule pathways C_LI

cell biology↗

bioRxiv2025

AFM-based nanoscale characterization of physical interaction within hematopoietic stem cells niche at single-cell level

Hematopoietic stem cells (HSCs) produce all blood cells throughout the lifespan of the organism. HSC requires a specialized bone marrow microenvironment, known as the niche, for proper differentiation and self-renewal. While several molecular and cellular elements of the niche are described, the precise understanding of the mechanobiology underlying HSC adhesion to the niche remains poorly understood. Here, we aim to characterize physical interactions and adhesion within the hematopoietic niche by combining cell sorting, surface functionalization, and atomic force microscopy. Using this approach, we quantified and compared the adhesion of bone marrow (BM) mesenchymal stromal cells (MSCs) to different extracellular proteins, as well as the adhesion of HSCs to MSCs. We observed that MSCs adhere with the greatest force to fibronectin in an Arg-Gly-As (RGD) motif mediated and actin cytoskeleton-dependent manner. Additionally, we showed that HSCs strongly adhere to MSC within 30 seconds and that the binding is RGD-independent. In conclusion, we demonstrated how to implement atomic force microscopy to measure the physiological interactions within the HSCs niche in a direct, specific, and quantitative way. This approach provides a more comprehensive and precise characterization of the biology of the HSC niche compared to previously used methods. Furthermore, it highlights the complexity of studying extremely small structures and rare cell populations in biophysical experiments.

cell biology↗

bioRxiv2024

Dose- and time-dependent effects of cobalt protoporphyrin IX on granulocyte mobilization and metabolic markers in mice

Recombinant granulocyte colony-stimulating factor (G-CSF) is the most commonly used agent for treating neutropenia and mobilizing hematopoietic stem cells (HSCs) for transplantation. However, some patients do not respond effectively to existing mobilization protocols. To address this, the development of new therapeutic approaches is necessary. One potential strategy is the pharmacological induction of endogenous mobilizing factors, which can be achieved through the administration of cobalt protoporphyrin IX (CoPP). CoPP induces mobilization of HSCs and granulocytes by increasing endogenous G-CSF production, though the optimal dosing and potential side effects remain unclear. The aim of our study was to optimize the dose and timing of CoPP administration and evaluate its safety in mobilizing cells from the bone marrow to the blood. Our results show that CoPP exerts a dose-dependent mobilizing effect, with the highest G-CSF levels and number of mobilized leukocytes observed in mice treated with 10 mg/kg of CoPP. While there were no severe adverse effects, there were mild fluctuations in markers of liver and kidney function, including a slight reduction in urea nitrogen (BUN) and glucose levels during the five days of administration. Additionally, although most parameters normalized within 30 days after treatment, the decrease in BUN persisted. Mice experienced short-term weight loss following CoPP administration, but they regained their initial weight within two weeks. By day 30, leukocyte counts, hematopoietic stem and progenitor cells (HSPCs) in bone marrow, and G-CSF concentration in the blood had returned to baseline. This study demonstrates that CoPP mobilizes cells from the bone marrow to the blood in a dose-dependent manner, with mild side effects, including temporary changes in biochemical markers and a sustained reduction in BUN levels.

pharmacology and toxicology↗

bioRxiv2023

Pauperization of Emerin from nuclear envelope drives prostate cancer cell migration and invasiveness

Micronuclei (MN) can arise from many causes, including the breakage of aberrant cytokinetic chromatin bridge. The frequent observation of MN in tumors raises the specter that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we test the hypothesis that the presence of micronuclei could induce specific phenotypic and functional changes to the cell and lead to increased cancer invasive potential. With a variety of imaging and molecular methods in vitro and in clinical samples from prostate cancer (PCa) patients, we show that chromosome bridge resolution can lead to EMD accumulation and formation of EMD-rich MN. Such structure is negative for Lamin A/C and positive for LBR and Sec6{beta}. It can cause EMD pauperization from NE affecting migratory and invasive properties of a cell and can be translated to PCa patients poor prognosis.

cancer biology↗

bioRxiv2022

CHIP ubiquitin ligase is involved in the nucleolar stress management

The nucleolus is a dynamic nuclear biomolecular condensate involved in cellular stress response. Under proteotoxic stress, the nucleolus can store damaged proteins for refolding or degradation. HSP70 chaperone is a well-documented player in the recovery process of proteins accumulated in the nucleolus after heat shock. However, little is known about the involvement of the ubiquitin-proteasome system in the turnover of its nucleolar clients. Here we show that HSP70, independently of its ATPase activity, promotes migration of the CHIP (carboxyl terminus of HSC70-interacting protein) ubiquitin ligase into the granular component of the nucleolus, specifically after heat stress. We show that while in the nucleolus, CHIP retains mobility that depends on its ubiquitination activity. Furthermore, after prolonged exposure to heat stress, CHIP self-organizes into large, intra-nucleolar droplet-like structures whose size is determined by CHIP ubiquitination capacity. Using a heat-sensitive nucleolar protein luciferase, we show that excess CHIP impairs its regeneration, probably through deregulation of HSP70. Our results demonstrate a novel role for CHIP in managing nucleolar proteostasis in response to stress.

cell biology↗

bioRxiv2020

Nutritional status and fecundity are synchronised by muscular exopheresis

Organismal functionality and reproduction depend on metabolic rewiring and balanced energy resources. However, the crosstalk between organismal homeostasis and fecundity, and the associated paracrine signaling mechanisms are still poorly understood. Using the Caenorhabditis elegans we discovered that large extracellular vesicles termed exophers, attributed in neurons and cardiomyocytes to the removal of damaged subcellular components, are released by body wall muscles to support embryonic growth. We found that exopher formation (exopheresis) is a non-cell autonomous process regulated by egg formation in the uterus. Our data suggest that exophers serve as transporters for muscle-generated yolk proteins used for nourishing and improving the growth rate of the next generation. We propose that the primary role of muscular exopheresis is to stimulate the reproductive capacity, thereby influencing the adaptation of worm populations to the current environmental conditions.

physiology↗