Biology subjects

Kaya, Z.

Publications and source records attributed to Kaya, Z..

5 recordsLinked to original sources

bioRxiv2026

Adaptive variation in drought-related traits across southern and central European white oak (Quercus sect. Quercus) populations

European white oaks grow from the Mediterranean coast to Southern Scandinavia, a huge environmental gradient that has likely fostered environmental adaptation. In the face of climate change, leveraging adaptations through assisted gene flow could help improve drought tolerance and maintain forest health, but requires an understanding of the species-specific patterns of adaptation to be successful at the target location. In this study, three common gardens were established in Switzerland, Tuerkiye, and Austria for two European white oak species (Quercus robur, and Q. pubescens) using provenances from Central and Southern Europe. Almost 900 oak seedlings were measured at key water-use efficiency and life history traits for their first two year of life and genotyped with low coverage whole-genome sequencing. Trait heritability and environmental adaptation were then explored through pedigree-free animal models, while the genomic architecture of traits was mapped using a genome wide association study ("GWAS"). Across the species, the heritability of measured traits was moderate to high, but common garden had a strong impact, signalling an environmental effect on the phenotype. Adaptation to precipitation seasonality was detected in key productivity and growth traits for both species, but had a small effect on absolute trait values. The GWAS identified a striking 150 kbp association in the Cyclic Nucleotide-Gated Ion Channel gene family with leaf d13C values. This gene family is involved in stomata opening and likely impacts the intrinsic water use efficiency under stress. Together, the strong signals of phenotypic plasticity and rather weak signals of climatic adaptation in seedlings suggest that assisted gene flow in these two white oaks is relevant only for highly drought-sensitive populations, if conducted managers should focus on seeds sources with high precipitation seasonality and smaller leaf sizes.

evolutionary biology↗

bioRxiv2025

High cholesterol increases myeloma tumour burden and promotes resistance to bortezomib

Multiple myeloma (MM) is an incurable hematologic cancer where malignant plasma cells accumulate in the bone marrow (BM), with disease progression highly dependent on cellular interactions. Obesity is a major risk factor for myeloma, however the underlying mechanisms are unclear. Here we used a murine myeloma model to show that a high cholesterol diet increases local and circulating levels of low density lipoprotein cholesterol (LDL), increasing bone marrow tumour burden in vivo. Exogenous LDL induced bortezomib-specific drug resistance in metabolically stressed myeloma cells in vitro and ex vivo. RNA-seq analysis revealed bortezomib-induced changes in the cholesterol biosynthesis/homeostasis pathway that were completely reverted with LDL pretreatment. In silico analysis of patient data supported a role for cholesterol in response to bortezomib-based therapies. Targeted proteome profiling revealed changes in expression of the adipokine resistin in the bone marrow of cholesterol-treated or myeloma-bearing mice, with elevated resistin expression observed in MGUS patients. Bone marrow adipocytes were found to be a major source of resistin, which was further increased in response to LDL. In summary, we demonstrate that high cholesterol promotes both myeloma development and bortezomib resistance, identifying resistin as a potential mediator so revealing new mechanisms underlying myeloma pathogenesis.

cancer biology↗

bioRxiv2024

Proline-2'-deoxymugineic acid (PDMA) increases seed quality and yield by alleviating iron deficiency symptoms in soybean under calcareous-alkaline conditions

Iron (Fe) deficiency in crops, particularly in calcareous-alkaline soils, poses a major challenge due to Fe immobilization. While synthetic chelators like EDTA and EDDHA are commonly used to improve Fe availability, proline-2-deoxymugineic acid (PDMA) has emerged as a promising alternative, enhancing Fe nutrition in crops such as rice and cucumber. This study aimed to assess the effectiveness of PDMA on soybean growth and yield under calcareous-alkaline conditions. A pot trial demonstrated that PDMA improves Fe uptake, translocation, and storage in soybeans, leading to increased chlorophyll content, and enhanced root and shoot growth. Even at low dosages, PDMA significantly improved plant development, with the highest dosage (30 M) resulting in notable increases in Fe, Zn, Mn, and Mg concentrations in roots, leaves, and seeds, surpassing the effects of the synthetic chelator Fe-EDDHA in several parameters. Additionally, 30 M PDMA substantially boosted soybean yield, increasing pod and seed number, and 100-seed weight. It also improved seed quality by increasing protein and oil content. These findings suggest that PDMA offers a sustainable, effective alternative to traditional Fe chelators, providing a viable solution for addressing Fe deficiency and enhancing crop biofortification in challenging soil conditions.

plant biology↗

bioRxiv2023

Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features

Extension of prostate cancer beyond the primary site into the surrounding organs by local invasion or nodal metastasis is associated with poor prognosis. The emergence and evolution of cancer clones at this early stage of expansion and spread has not been studied in detail. We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes. Based on these data, we delineated the route of tumour progression and metastasis following the transformation of adenocarcinoma to amphicrine morphology, the molecular events leading to whole genome duplication associated with a single clonal expansion and identified putative driver events associated with local invasion and lymph node metastasis. We also correlated genomic changes associated with differences in morphology and identified putative driver events associated with spread to seminal vesicle invasion and lymph node metastasis. Taken together, these findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes associated with morphological transformation. Our results demonstrate the value of integrating multi-region sequencing with histopathological data to study tumour evolution and identify mechanisms of prostate cancer spread.

cancer biology↗

bioRxiv2021

Cerebrospinal fluid outflow through skull channels instructs cranial hematopoiesis

Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues, particularly dural lymphatic vessels that allow cerebrospinal fluid outflow, facilitate intersystem communication. Here we observe that cerebrospinal fluid exits into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria usurp this perivascular route to infect the skulls hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. Because skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in cerebrospinal fluid by regional marrow has broad implications for neurological disorders. One-Sentence SummarySkull channels transport cerebrospinal fluid from the subarachnoid space to the cranial bone marrow via a perivascular route, which bacteria use during meningitis.

immunology↗