MaxHiC: A robust background correction model to identify biologically relevant chromatin interactions in Hi-C and capture Hi-C experiments

Hi-C is a genome-wide chromosome conformation capture technology that detects interactions between pairs of genomic regions and exploits higher order chromatin structures. Conceptually Hi-C data counts interaction frequencies between every position in the genome and every other position. Biologically functional interactions are expected to occur more frequently than transient background and artefactual interactions. To identify biologically relevant interactions, several background models that take biases such as distance, GC content and mappability into account have been proposed. Here we introduce MaxHiC, a background correction tool that deals with these complex biases and robustly identifies statistically significant interactions in both Hi-C and capture Hi-C experiments. MaxHiC uses a negative binomial distribution model and a maximum likelihood technique to correct biases in both Hi-C and capture Hi-C libraries. We systematically benchmark MaxHiC against major Hi-C background correction tools including Hi-C significant interaction callers (SIC) and Hi-C loop callers using published Hi-C, capture Hi-C, and Micro-C datasets. Our results demonstrate that 1) Interacting regions identified by MaxHiC have significantly greater levels of overlap with known regulatory features (e.g. active chromatin histone marks, CTCF binding sites, DNase sensitivity) and also disease-associated genome-wide association SNPs than those identified by currently existing models, 2) the pairs of interacting regions are more likely to be linked by eQTL pairs and 3) more likely to link known regulatory features including known functional enhancer-promoter pairs validated by CRISPRi than any of the existing methods. We also demonstrate that interactions between different genomic region types have distinct distance distributions only revealed by MaxHiC. MaxHiC is publicly available as a python package for the analysis of Hi-C, capture Hi-C and Micro-C data.     

Heterogeneous effects of cholecystokinin on neuronal response properties in deep layers of rat barrel cortex

Abstract

Cholecystokinin (CCK) is one of the most studied neuropeptides in the brain. In this study, we investigated the effects of CCK-8s and LY225910 (CCK₂ receptor antagonist) on properties of neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. This study was done on 20 male Wistar rats, weighing 230–260?g. CCK-8s (300?nmol/rat) and LY225910 (1?µmol/rat) were administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in the barrel cortex using tungsten microelectrodes. Computer controlled mechanical displacement was used to deflect whiskers individually or in combination at 30?ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interaction. ICV administration of CCK-8s and LY225910 had heterogeneous effects on neuronal spontaneous activity, ON and OFF responses to PW and/or AW deflections, and CTR for both ON and OFF responses. The results of this study demonstrated that CCK-8s can modulate neuronal response properties in deep layers of rat barrel cortex probably via CCK₂ receptors.     

Integrative effects of stress- and stress tolerance-inducing elicitors on in vitro bioactive compounds of ajowan [Trachyspermum ammi (L.) Sprague] medicinal plant

Plant Cell, Tissue and Organ Culture (PCTOC) - In the present study, the integrative effects of two sets of stress tolerance-inducing and stress-inducing elicitors, including polyethylene...     

MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle,apoptosis, and proliferation

Molecular Biology Reports - Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the...     

miR-200c-3p upregulation and ACE2 downregulation via bacterial LPS and LTA as interesting aspects for COVID-19 treatment and immunity

Molecular Biology Reports -     

New Insight into the Interactions of Arbutin with Mushroom Tyrosinase

The Protein Journal - As a safe substitute for hydroquinone, β-arbutin, a natural plant substance, and its synthetic counterpart, α-arbutin, are used in depigmentation formulations....     

The survivin molecule as a double-edged sword in cellular physiologic and pathologic conditions and its role as a potential biomarker and therapeutic target in cancer

Survivin is a member of the family of apoptosis inhibitory proteins with increased expression level in most cancerous tissues. Evidence shows that survivin plays regulatory roles in proliferation or survival of normal adult cells, principally vascular endothelial cells, T lymphocytes, primitive hematopoietic cells, and polymorphonuclear neutrophils. Survivin antiapoptotic role is, directly and indirectly, related to caspase proteins and shows its role in cell division through the chromosomal passenger complex. Survivin contains many genetic polymorphisms that the role of some variations has been proven in several cancers. The −31G/C polymorphism is one of the most important survivin mutations which is located in the promoter region on a CDE/CHR motif. This polymorphism can upregulate the survivin messenger RNA. In addition, its allele C can increase the risk of cancers in 1.27-fold than allele G. Considering the fundamental role of survivin in different cancers, this protein could be considered as a new therapeutic target in cancer treatment. For this purpose, various strategies have been designed including the prevention of survivin expression through inhibition of mRNA translation using antagonistic molecules, inhibition of survivin gene function through small inhibitory molecules, gene therapy, and immunotherapy. In this study, we describe the structure, played roles in physiological and pathological states and genetic polymorphisms of survivin. Finally, the role of survivin as a potential target in cancer therapy given challenges ahead has been discussed.     

Astrocyte- neuron interaction as a mechanism responsible for generation of neural synchrony: a study based on modeling and experiments

Neural synchronization is considered as an important mechanism for information processing. In addition, based on recent neurophysiologic findings, it is believed that astrocytes regulate the synaptic transmission of neuronal networks. Therefore, the present study focused on determining the functional contribution of astrocytes in neuronal synchrony using both computer simulations and extracellular field potential recordings. For computer simulations, as a first step, a minimal network model is constructed by connecting two Morris-Lecar neuronal models. In this minimal model, astrocyte-neuron interactions are considered in a functional-based procedure. Next, the minimal network is extended and a biologically plausible neuronal population model is developed which considers functional outcome of astrocyte-neuron interactions too. The employed structure is based on the physiological and anatomical network properties of the hippocampal CA1 area. Utilizing these two different levels of modeling, it is demonstrated that astrocytes are able to change the threshold value of transition from synchronous to asynchronous behavior among neurons. In this way, variations in the interaction between astrocytes and neurons lead to the emergence of synchronous/asynchronous patterns in neural responses. Furthermore, population spikes are recorded from CA1 pyramidal neurons in rat hippocampal slices to validate the modeling results. It demonstrates that astrocytes play a primary role in neuronal firing synchronicity and synaptic coordination. These results may offer a new insight into understanding the mechanism by which astrocytes contribute to stabilizing neural activities.