Biology subjects

Yilmaz, M.

Publications and source records attributed to Yilmaz, M..

22 records · Page 2Linked to original sources

bioRxiv2022

Cryogenic X-ray crystallographic studies of biomacromolecules at Turkish Light Source: Turkish DeLight

X-ray crystallography is a robust and powerful structural biology technique that provides high-resolution atomic structures of biomacromolecules. Scientists use this technique to unravel mechanistic and structural details of biological macromolecules (e.g. proteins, nucleic acids, protein complexes, protein-nucleic acid complexes, or large biological compartments). Since its inception, single-crystal cryo-crystallography has never been performed in Turkiye due to the lack of a single-crystal X-ray diffractometer. The X-ray diffraction facility recently established at the University of Health Sciences, Istanbul, Turkiye will enable Turkish and international researchers to easily perform high-resolution structural analysis of biomacromolecules from single crystals. Here, we describe the technical and practical outlook of a state-of-the-art home-source X-ray, using lysozyme as a model protein. The methods and practice described in this article can be applied to any biological sample for structural studies. Therefore, this article will be a valuable practical guide from sample preparation to data analysis.

biophysics↗

bioRxiv2022

De novo mass spectrometry peptide sequencing with a transformer model

Tandem mass spectrometry is the only high-throughput method for analyzing the protein content of complex biological samples and is thus the primary technology driving the growth of the field of proteomics. A key outstanding challenge in this field involves identifying the sequence of amino acids--the peptide--responsible for generating each observed spectrum, without making use of prior knowledge in the form of a peptide sequence database. Although various machine learning methods have been developed to address this de novo sequencing problem, challenges that arise when modeling tandem mass spectra have led to complex models that combine multiple neural networks and post-processing steps. We propose a simple yet powerful method for de novo peptide sequencing, Casanovo, that uses a transformer framework to map directly from a sequence of observed peaks (a mass spectrum) to a sequence of amino acids (a peptide). Our experiments show that Casanovo achieves state-of-the-art performance on a benchmark dataset using a standard cross-species evaluation framework which involves testing with spectra with never-before-seen peptide labels. Casanovo not only achieves superior performance but does so at a fraction of the model complexity and inference time required by other methods.

bioinformatics↗

bioRxiv2020

Nucleolin is expressed in human fetal brain development and reactivated in human glial brain tumors regulating angiogenesis and vascular metabolism

Glioblastoma (GBM) is amongst the deadliest human cancers and is characterized by high levels of vascularisation. Angiogenesis is highly dynamic during brain development and almost quiescent in the adult brain, but is reactivated in vascular-dependent CNS pathologies such as brain tumors. Nucleolin (NCL) is a known regulator of cell proliferation and angiogenesis, but its roles on physiological and pathological brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit (NVU) in human fetal brains and human gliomas in vivo as well as its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial- and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression in tumor- and blood vessel cells correlated with glioma malignancy in vivo. In culture, siRNA-mediated NCL knockdown reduced human umbilical vein endothelial cell (HUVEC) sprouting angiogenesis, proliferation and filopodia extension, and reduced glucose metabolism. Mechanistically, RNA sequencing of Nucleolin knockdown in HUVECs revealed a putative p53-TIGAR-HK2 regulation of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that positively regulates sprouting angiogenesis and endothelial metabolism. Our findings have important implications in therapeutic targeting of glioma.

neuroscience↗

bioRxiv2017

Topographical and spectral signatures of infant and adult movement artifacts in naturalistic EEG

Electroencephalography (EEG) is perhaps the most widely used brain-imaging technique for paediatric populations. However, EEG signals are prone to distortion by motion. Compared to adults, infants motion is both more frequent and less stereotypical yet motion effects on the infant EEG signal are largely undocumented. Here, we present a systematic assessment of naturalistic motion effects on the infant and adult EEG signal. In Study 1, we documented the prevalence of 27 naturally occurring facial and body motions by video-coding five mother-infant pairs during naturalistic play. In Study 2, we elicited a subset of the most common facial, limb and postural motions from one adult and one infant actor while their EEG was recorded. In Study 3, we recorded EEG signals from a larger group of 12 infants whilst they produced the same motions spontaneously. Our findings from Study 2 suggested that adult movements mainly generated increases in spectral power relative to resting state, primarily at peripheral sites and in delta and high-beta frequency bands. In infants, both elicited motions (N=1, Study 2) and spontaneously-occurring motions (N=12, Study 3) produced decreases in theta, alpha and beta power over central regions and increased beta/delta power at peripheral sites. We also observed that infants jaw and upper limb movements generated more pronounced EEG artifacts than lower limb movements. It is intended that this work will inform future development of methods for addressing EEG motion-related artifacts and support wider use of naturalistic paradigms in social and developmental neuroscience.

neuroscience↗