Biology subjects

Naghizadeh, M.

Publications and source records attributed to Naghizadeh, M..

4 recordsLinked to original sources

bioRxiv2026

Comprehensive analysis of nonsense-mediated mRNA decay targets and activity in cardiomyocytes

Nonsense-mediated mRNA decay (NMD) serves as a mechanism to suppress the expression of mutant alleles containing premature termination codons, limit the expression of aberrantly spliced transcript isoforms, and control the expression of numerous regular genes. While the principles by which NMD recognizes target transcripts are well understood, much less is known about the range of mRNAs subject to NMD in tissues and specialized cell types. Here we describe the landscape of genes whose expression is controlled by NMD in cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CM), using small read RNA sequencing in combination with a potent inhibitor of SMG1, a kinase essential for NMD. We find that NMD targets are highly conserved between iPSC-CM lines derived from two healthy individuals. Beyond gene level analysis, we identify individual exon and intron RNA sequences that strongly accumulate upon SMG1 inhibition. Using the cardiac NMD targets identified at gene, exon and intron level, we then demonstrate reduced NMD efficiency upon knockdown of two essential NMD factors, UPF1 and UPF2, in iPSC-CM. Our analysis demonstrates that quantifying the transcriptome-wide response to SMG1 inhibition represents a highly sensitive approach to assess global activity of the NMD pathway.

molecular biology↗

bioRxiv2024

IgM plays a prominent role in naturally acquired immunity against Plasmodium falciparum gametocytes

The development of transmission-blocking vaccines against Plasmodium falciparum malaria could facilitate malaria elimination. However, limitations in the knowledge of the human immune responses against P. falciparum transmission stages, known as gametocytes, represent a critical roadblock to vaccine development. We evaluated human antibodies acquired through natural malaria exposure to whole gametocytes and recombinant antigens expressed by transmission stages, including the major transmission-blocking vaccine candidates Pfs230 and Pfs48/45 and other transmission stages, Pf38, Pf12 and Pf41. Among individuals residing in Kenya and Papua New Guinea, we found substantial antibody responses to whole gametocytes and to all recombinant transmission stage antigens with high levels of IgG, IgG subclasses and IgM. Complement fixation by antibodies to gametocytes is key for effective transmission-blocking activity. We found that purified IgM was substantially more potent than IgG at mediating complement fixation and activation. Higher antibody levels were generally observed in individuals positive for P. falciparum infection, including gametocyte positive individuals, and these antibodies generally increased with age. Our findings reveal that IgM is a prominent feature of antibody responses to gametocytes and that antibodies target multiple antigens. The further demonstration that IgM has high functional activity against gametocytes suggests IgM plays an important role in immunity to transmission stages. Our data provide new insights to inform the development of potent transmission-blocking vaccines.

immunology↗

bioRxiv2022

Regional variation in cholinergic terminal activity determines the non-uniform occurrence of cortical slow-wave activity during REM sleep

Sleep consists of two basic stages: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is characterized by slow high-amplitude cortical EEG signals, while REM sleep is characterized desynchronized cortical rhythms. While, until recently, it has been widely believed that cortical activity during REM sleep is globally desynchronized, recent electrophysiological studies showed slow waves (SW) in some cortical areas during REM sleep. Electrophysiological techniques, however, have been unable to resolve the regional structure of these activities, due to relatively sparse sampling. We mapped functional gradients in cortical activity during REM sleep using mesoscale imaging in mice, and observed local SW patterns occurring mainly in somatomotor and auditory cortical regions, with minimum presence within the default mode network. The role of the cholinergic system in local desynchronization during REM sleep was also explored by calcium imaging of cholinergic terminal activity within the mouse cortex. Terminal activity was weaker in regions exhibiting SW activity more frequently during REM sleep. We also analyzed Allen Mouse Brain Connectivity dataset and found that these regions have weaker cholinergic projections from the basal forebrain.

neuroscience↗

bioRxiv2017

Quaddles: A multidimensional 3D object set with parametrically-controlled and customizable features

Many studies of vision and cognition require novel three-dimensional object sets defined by a parametric feature space. Creating such sets and verifying that they are suitable for a given task, however, can be extremely time-consuming and effortful. Here we present a new set of multidimensional objects, Quaddles, designed for a study of feature-based learning and attention, but adaptable for many research purposes. Quaddles have features that are all equally-visible from any angle around the vertical axis, and which all have similar response biases on a feature detection task, thus removing one potential source of bias in object selection. They are available as two-dimensional images, rotating videos, and FBX object files suitable for use with any modern video game engine. We also provide examples and tutorials for modifying Quaddles or creating completely new object sets from scratch, hopefully greatly speeding up the development time of future novel object studies.\n\nAuthors noteThis work was supported by grant MOP 102482 from the Canadian Institutes of Health Research (TW) and by the Natural Sciences and Engineering Research Council of Canada Brain in Action CREATE-IRTG program (MRW, TW). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of this manuscript. Authors would like to thank Hongying Wang for technical support, and Isabel Gauthier for comments on a draft version of the manuscript.\n\nThe study described herein was approved by the York University Office of Research Ethics (Certificate # 2016-214).\n\nA draft version of this manuscript is available online at BioR{chi}iv:

neuroscience↗