Biology subjects

Aziz, T.

Publications and source records attributed to Aziz, T..

5 recordsLinked to original sources

bioRxiv2026

Oocyte-stored Mif promotes preimplantation development as an embryonic extracellular signal

Mammalian preimplantation embryos develop more efficiently in groups than in isolation, suggesting that embryos secrete embryotrophic factors that promote development. However, the endogenous embryotrophic signals responsible for this long-recognized phenomenon remain incompletely defined. Using an unbiased proteomic screen for stable maternal proteins that may function as embryonic extracellular signals, we identified the cytokine macrophage migration inhibitory factor (Mif) as an abundant oocyte-stored protein that persists for several days after fertilization in mice. Quantitative measurements of spent culture medium reveal that developing embryos release Mif, with a substantial fraction derived from the maternal deposit. Extracellular Mif levels peak 3-4 days post fertilization, the same period when Mif knockout preimplantation embryos produce its strongest phenotype. Embryos lacking maternal, but not zygotic, Mif display defective blastocyst growth even in group culture. Individually cultured embryos exhibit similar blastocyst growth defects that can be rescued by supplementing recombinant Mif at physiologically relevant concentrations. Mif activates the PI3K-Akt-mTORC1 pathway through the cell-surface receptor Cd74 to promote blastocyst growth and cell proliferation. Together, these findings identify Mif as a potential endogenous contributor to the density-dependent embryotrophic effects and reveal that maternally stored proteins may function long after fertilization as extracellular signaling molecules to support preimplantation development in mammals.

developmental biology↗

bioRxiv2025

Stage- and tissue-specific gene editing using 4-OHT inducible Cas9 in whole organism

Vertebrate genes usually function in specific tissues at specific stages, and thus their functional studies require conditional knockout or editing. In the zebrafish, spatiotemporally inducible genome editing, especially during early embryonic development, is still challenging. Here, we report inducible Cas9-based gene editing in specific cell types at desired stages in zebrafish. We show that the nCas9ERT2 fusion protein consisting of Cas9 and estrogen receptor flanked by two nuclear localization signals is normally located in the cytoplasm and efficiently translocated into the nucleus upon 4-hydroxytamoxifen (4-OHT) treatment in cultured cells or embryos. As a proof-of-concept, we demonstrate that target genes in primordial germ cells or germ cells of transgenic zebrafish embryos or adults with stable expression of nCas9ERT2 and gene-specific guide RNAs (gRNAs) can be induced to mutate by application of 4-OHT. This inducible nCas9ERT2 system also works in mouse early embryos. Thus, this inducible gene editing approach will be another choice for studying the temporospatial function of genes at the organismal level. Hence, the inducible nCas9ERT2 system expands the tissue- and stage-specific gene editing toolkit.

developmental biology↗

bioRxiv2021

Neural Oscillatory Characteristics of Feedback Associated Activity in Globus Pallidus Interna

Neural oscillatory activities in basal ganglia have prominent roles in cognitive processes on local and global scales. However, the characteristics of high frequency oscillatory activities during cognitive tasks have not been extensively explored in human Globus Pallidus internus (GPi). This study aimed to investigate amplitude and interhemispheric coupling of bilateral GPi high gamma bursts in dystonia and Parkinsons Disease (PD) patients, in on and off medication states, after feedback during the Intra-Extra-Dimension shift (IED) task. Bilateral GPi Local Field Potentials (LFP) activity was recorded via externalized DBS electrodes during the IED task. Inter hemisphere phase synchrony was assessed using Inter-Site Phase Clustering (ISPC). Transient high gamma activity ([~]100-150Hz) was observed immediately after feedback in the dystonia patient. Moreover, these bursts were phase synchronous between left and right GPis with an antiphase clustering of phase differences. In contrast, no synchronous high gamma activity was detected in the PD patient with or without dopamine administration. The off-med PD patient displayed enhanced low frequency clusters ameliorated by medication in the on-med state. Furthermore, an increased low frequency activity was observed after feedback of incorrect trials in both disease states. The current study provides a rare report of antiphase homotopic synchrony in human GPi, potentially related to incorporating and processing feedback information. The absence of these activities in off and on-med PD indicates the potential presence of impaired medication independent circuits related to feedback processing. Together, these findings are helpful in pointing to the potential role of GPis synchronized high frequency activity in cognitive tasks and feedback information processing.

neuroscience↗

bioRxiv2021

CAT, AGTR2, L-SIGN and DC-SIGN are potential receptors for the entry of SARS-CoV-2 into human cells

Since December 2019, the COVID-19 caused by SARS-CoV-2 has been widely spread all over the world. It is reported that SARS-CoV-2 infection affects a series of human tissues, including lung, gastrointestinal tract, kidney, etc. ACE2 has been identified as the primary receptor of the SARS-CoV-2 Spike (S) protein. The relatively low expression level of this known receptor in the lungs, which is the predominantly infected organ in COVID-19, indicates that there may be some other co-receptors or alternative receptors of SARS-CoV-2 to work in coordination with ACE2. Here, we identified twenty-one candidate receptors of SARS-CoV-2, including ACE2-interactor proteins and SARS-CoV receptors. Then we investigated the protein expression levels of these twenty-one candidate receptors in different human tissues and found that five of which CAT, MME, L-SIGN, DC-SIGN, and AGTR2 were specifically expressed in SARS-CoV-2 affected tissues. Next, we performed molecular simulations of the above five candidate receptors with SARS-CoV-2 S protein, and found that the binding affinities of CAT, AGTR2, L-SIGN and DC-SIGN to S protein were even higher than ACE2. Interestingly, we also observed that CAT and AGTR2 bound to S protein in different regions with ACE2 conformationally, suggesting that these two proteins are likely capable of the co-receptors of ACE2. Conclusively, we considered that CAT, AGTR2, L-SIGN and DC-SIGN were the potential receptors of SARS-CoV-2. Moreover, AGTR2 and DC-SIGN tend to be highly expressed in the lungs of smokers, which is consistent with clinical phenomena of COVID-19, and further confirmed our conclusion. Besides, we also predicted the binding hot spots for these putative protein-protein interactions, which would help develop drugs against SARS-CoV-2.

bioinformatics↗

bioRxiv2019

Dynamic changes in rhythmic and arrhythmic neural signatures in the subthalamic nucleus induced by anaesthesia and intubation

BackgroundSubcortical structures including the basal ganglia have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. However, how basal ganglia contributes to the loss and recovery of consciousness during anaesthesia has not been well characterized.\n\nMethodsIn this study, using local field potentials (LFPs) from subthalamic nucleus (STN) and scalp electroencephalogram in 12 Parkinsons disease patients, we investigate STN neural signatures during propofol general anaesthesia and during intubation as an arousal intervention in anaesthesia.\n\nResultsPropofol-induced anaesthesia resulted in changes in multiple frequency bands in STN LFPs, including increased low-frequency activities (slow-wave oscillation, delta, theta, and alpha bands) and decreased higher-frequency activities. This was also accompanied by increased STN-frontal cortical coherence in alpha frequency band. Beta and high-gamma activities in the STN temporally increased during intubation compared to the status of loss of consciousness. We also show that the dynamic changes in the high frequency activities (80-180 Hz) in STN LFPs induced by propofol and intubation correlated with power-law exponent in the power spectra between 2 and 80 Hz.\n\nConclusionsOur findings suggest that anaesthesia and intubation induced changes in the STN LFPs in multiple frequency bands. They are also consistent with the hypothesis that the power-law exponent in the power spectra between 2 and 80 Hz reflect the excitation/inhibition balance in the STN, which is modulated by anaesthesia and intubation, and further modulate the high frequency activity.

neuroscience↗