Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene Cirbp.

In mammals, body temperature fluctuates diurnally around a mean value of 36°C-37°C. Despite the small differences between minimal and maximal values, body temperature rhythms can drive robust cycles in gene expression in cultured cells and, likely, animals. Here we studied the mechanisms responsible for the temperature-dependent expression of cold-inducible RNA-binding protein (CIRBP). In NIH3T3 fibroblasts exposed to simulated mouse body temperature cycles, Cirbp mRNA oscillates about threefold in abundance, as it does in mouse livers. This daily mRNA accumulation cycle is directly controlled by temperature oscillations and does not depend on the cells' circadian clocks. Here we show that the temperature-dependent accumulation of Cirbp mRNA is controlled primarily by the regulation of splicing efficiency, defined as the fraction of Cirbp pre-mRNA processed into mature mRNA. As revealed by genome-wide "approach to steady-state" kinetics, this post-transcriptional mechanism is widespread in the temperature-dependent control of gene expression.

Female infertility and dietary antioxidant index (DAI); a case-control study.

BACKGROUND: Adequate intake of natural antioxidants may improve female fertility. The aim of this study was to examine the link between female infertility and dietary antioxidant index (DAI). METHODS: This case-control study was conducted on 125 women with recently diagnosis of reduced ovarian reserves (AMH < 1.1) as the case group and 125 women with normal ovarian reserve as the control group in Rasht, Iran. The amount of food intake was assessed using the food frequency questionnaire (FFQ) and the DAI was calculated to estimate the antioxidant capacity of the diet. RESULTS: Regarding dietary intake, the infertile women had a lower intake of potassium (2789.25 ± 777 vs. 2593.68 ± 443 mg/d, P = 0.02), magnesium (204.12 ± 66 vs. 189.73 ± 34 mg/d, P = 0.03), copper (0.93 ± 0.40 vs. 0.82 ± 0.20 mg/d, P < 0.01), vitamin C (133.99 ± 46 vs. 122.62 ± 24 mg/d, P = 0.02), and fiber (14.53 ± 3 vs. 13.44 ± 2 g/d, P < 0.05), and a higher intake of cholesterol (205.61 ± 58 vs. 227.02 ± 46 mg/d, P < 0.01) than the control group (All P < 0.05). The DAI was negatively associated with infertility (OR: 0.94, CI 95%: 0.88-0.97, P = 0.03). The association remained significant after adjustments for age, BMI, the underlying diseases, fertility frequency, IVF failure, and calorie intake. CONCLUSION: Following an antioxidant-rich diet may reduce the risk of infertility. More longitudinal studies are warranted to confirm these results and discover the underlying mechanisms.

The effects of FTO gene rs9939609 polymorphism on the association between breast cancer and dietary intake.

Breast cancer (BC) is the leading cause of cancer-related deaths in females worldwide and is related to genetic and environmental factors. Dietary components may strongly influence the risk of BC. A possible association was also reported between the fat mass and obesity-associated (FTO) single-nucleotide polymorphisms (SNPs) and BC. This study aimed to investigate the impact of FTO rs9939609 polymorphism on the association between BC and dietary intake. This study was conducted on 180 women with BC as the case group and 360 healthy women as the control group. The dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The FTO gene was genotyped for rs9939609 polymorphism. After adjusting the confounding variables, there was no significant association between dietary intake and BC in individuals without risk allele. A positive association between dietary intake of omega-6 fatty acids and BC was found only in individuals with risk allele of FTO gene (OR: 1.31, 95% CI: 1.08-1.60, p: 0.006). FTO gene risk allele may influence the effect of diet on breast cancer risk. Further studies are needed to assess the possible effects of the FTO genotype on the association between BC risk and dietary components.

Crunch: integrated processing and modeling of ChIP-seq data in terms of regulatory motifs.

Although ChIP-seq has become a routine experimental approach for quantitatively characterizing the genome-wide binding of transcription factors (TFs), computational analysis procedures remain far from standardized, making it difficult to compare ChIP-seq results across experiments. In addition, although genome-wide binding patterns must ultimately be determined by local constellations of DNA-binding sites, current analysis is typically limited to identifying enriched motifs in ChIP-seq peaks. Here we present Crunch, a completely automated computational method that performs all ChIP-seq analysis from quality control through read mapping and peak detecting and that integrates comprehensive modeling of the ChIP signal in terms of known and novel binding motifs, quantifying the contribution of each motif and annotating which combinations of motifs explain each binding peak. By applying Crunch to 128 data sets from the ENCODE Project, we show that Crunch outperforms current peak finders and find that TFs naturally separate into "solitary TFs," for which a single motif explains the ChIP-peaks, and "cobinding TFs," for which multiple motifs co-occur within peaks. Moreover, for most data sets, the motifs that Crunch identified de novo outperform known motifs, and both the set of cobinding motifs and the top motif of solitary TFs are consistent across experiments and cell lines. Crunch is implemented as a web server, enabling standardized analysis of any collection of ChIP-seq data sets by simply uploading raw sequencing data. Results are provided both in a graphical web interface and as downloadable files.

Investigation of factors related to the behavior of reporting clinical errors in nurses working in educational and medical centers in Rasht city, Iran.

BACKGROUND: Report of medical error is one of the effective components in the quality of healthcare services. A significant part of medical errors can be prevented by acting appropriately. The theory of planned behavior offers a framework in which the nurse intention to perform the behavior of error reporting is investigated. This study was conducted to determine the factors related to the behavior of reporting clinical errors in nurses working in educational and medical centers in Rasht based on the theory of planned behavior in 2020. METHODS: In this descriptive-analytical study, 326 nurses in all medical centers in Rasht were selected by the multi-stage random sampling method. Data collection tool was a valid and reliable questionnaire based on the theory of planned behavior. Data analysis was conducted using the SPSS software, analysis of variance, correlation, and linear regression. RESULTS: 39% of nurses reported that they had reported a medical error, and the average number of error reports per nurse during the last 3 months was 1.42 errors. The predictive power of the theory of behavioral intention was 47%, and predictive constructs were attitude (B = .43), perceived behavioral control (B = .33), and subjective norm (B = .04) using linear regression. The predictive power of the theory for nurses' behavior was 3.1%. None of the demographic variables played a role in predicting the behavior of nurses' reporting clinical error, and no behavioral intention predicted the behavior of nurses' reporting clinical errors. CONCLUSION: The theory of planned behavior expresses the factors affecting the behavior intention of nurses' reporting clinical errors satisfactorily. However, it was an inappropriate theory in behavior prediction. It appears that factors, such as fear of consequences of error reporting, social pressures by colleagues and officials, and lack of knowledge and skills required to identify medical errors, are the barriers to conversion of intention to the behavior of reporting clinical errors. It is necessary to provide the ground to increase nurses' report of clinical errors by acting appropriately.

The association between fat mass and obesity-associated (FTO) genotype and serum vitamin D level in breast cancer patients.

The preventive effect of vitamin D against breast cancer can be influenced by gene polymorphisms. This study aimed to investigate the association between serum level of 25(OH) vitamin D and FTO genotype in breast cancer patients. A cross-sectional study was carried out on 180 newly diagnosed patients with breast cancer in Tehran, Iran. The blood samples were collected from the participants in order to assess the FTO gene rs9939609 polymorphism by the tetra-primer amplification refractory mutation system (Tetra-ARMS) PCR method. The serum level of 25(OH) vitamin D was measured using the direct competitive enzyme-linked immunosorbent assay (ELISA) method. The association between vitamin D and the FTO genotype in patients with breast cancer was assessed after adjustment for cofounders. The frequency of TT, AT and AA genotypes in the breast cancer patients were 43% (n = 77), 49% (n = 89) and 8% (n = 14), respectively. All patients with higher than 40 ng/dl of serum 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele (p = 0.019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer.

Association of serum 25-OH-vitamin D level with FTO and IRX3 genes expression in obese and overweight boys with different FTO rs9930506 genotypes.

BACKGROUND: The roles of FTO gene and the level of serum 25-OH-vitamin D in obesity are frequently reported. This study aimed to investigate the interactions of serum 25-OH-vitamin D level, FTO and IRX3 genes expression, and FTO genotype in obese and overweight boys. METHODS: This study was carried out on the 120 male adolescents with overweight in Tehran, Iran. Blood samples were collected from the participants in order to evaluate the serum level of 25-OH-vitamin D, the expression level of FTO and IRX3 genes, and FTO genotype for rs9930506 at baseline and after 18 weeks of the study. RESULTS: In general, no significant association was found between serum 25-OH-vitamin D level and IRX3 and FTO genes expression. The results of linear regression on the relationship between 25-OH-vitamin D serum level and FTO and IRX3 genes expression based on FTO genotypes for rs9930506 indicated that in AA/AG genotype carriers, serum 25-OH-vitamin D level was positively associated with FTO gene expression (B = 0.07, p = 0.02) and inversely associated with IRX3 gene expression (B = - 0.07, p = 0.03). In GG carriers, serum 25-OH-vitamin D level was not associated with expression of IRX3 and FTO genes. CONCLUSION: There are significant interactions between 25-OH-vitamin D and the expression of FTO and IRX3 genes in the subset of obese patients with specific genotypes for FTO rs9930506. There was no association between serum 25-OH-vitamin D levels and the expression of FTO and IRX genes in individuals with a homozygous genotype for the risk allele of the FTO gene polymorphism.

Automated incorporation of pairwise dependency in transcription factor binding site prediction using dinucleotide weight tensors.

Gene regulatory networks are ultimately encoded by the sequence-specific binding of (TFs) to short DNA segments. Although it is customary to represent the binding specificity of a TF by a position-specific weight matrix (PSWM), which assumes each position within a site contributes independently to the overall binding affinity, evidence has been accumulating that there can be significant dependencies between positions. Unfortunately, methodological challenges have so far hindered the development of a practical and generally-accepted extension of the PSWM model. On the one hand, simple models that only consider dependencies between nearest-neighbor positions are easy to use in practice, but fail to account for the distal dependencies that are observed in the data. On the other hand, models that allow for arbitrary dependencies are prone to overfitting, requiring regularization schemes that are difficult to use in practice for non-experts. Here we present a new regulatory motif model, called dinucleotide weight tensor (DWT), that incorporates arbitrary pairwise dependencies between positions in binding sites, rigorously from first principles, and free from tunable parameters. We demonstrate the power of the method on a large set of ChIP-seq data-sets, showing that DWTs outperform both PSWMs and motif models that only incorporate nearest-neighbor dependencies. We also demonstrate that DWTs outperform two previously proposed methods. Finally, we show that DWTs inferred from ChIP-seq data also outperform PSWMs on HT-SELEX data for the same TF, suggesting that DWTs capture inherent biophysical properties of the interactions between the DNA binding domains of TFs and their binding sites. We make a suite of DWT tools available at dwt.unibas.ch, that allow users to automatically perform 'motif finding', i.e. the inference of DWT motifs from a set of sequences, binding site prediction with DWTs, and visualization of DWT 'dilogo' motifs.

Acoustofluidic Engineering Functional Vessel-on-a-Chip.

Construction of in vitro vascular models is of great significance to various biomedical research, such as pharmacokinetics and hemodynamics, thus is an important direction in tissue engineering. In this work, a standing surface acoustic wave field was constructed to spatially arrange suspended endothelial cells into a designated patterning. The cell patterning was maintained after the acoustic field was withdrawn by the solidified hydrogel. Then, interstitial flow was provided to activate vessel tube formation. Thus, a functional vessel-on-a-chip was engineered with specific vessel geometry. Vascular function, including perfusability and vascular barrier function, was characterized by beads loading and dextran diffusion, respectively. A computational atomistic simulation model was proposed to illustrate how solutes cross vascular lipid bilayer. The reported acoustofluidic methodology is capable of facile and reproducible fabrication of functional vessel network with specific geometry. It is promising to facilitate the development of both fundamental research and regenerative therapy.

Acoustofluidic Engineering of Functional Vessel-on-a-Chip.

Construction of in vitro vascular models is of great significance to various biomedical research, such as pharmacokinetics and hemodynamics, and thus is an important direction in the tissue engineering field. In this work, a standing surface acoustic wave field was constructed to spatially arrange suspended endothelial cells into a designated acoustofluidic pattern. The cell patterning was maintained after the acoustic field was withdrawn within the solidified hydrogel. Then, interstitial flow was provided to activate vessel tube formation. In this way, a functional vessel network with specific vessel geometry was engineered on-chip. Vascular function, including perfusability and vascular barrier function, was characterized by microbead loading and dextran diffusion, respectively. A computational atomistic simulation model was proposed to illustrate how solutes cross the vascular membrane lipid bilayer. The reported acoustofluidic methodology is capable of facile and reproducible fabrication of the functional vessel network with specific geometry and high resolution. It is promising to facilitate the development of both fundamental research and regenerative therapy.

The association among calorie, macronutrient, and micronutrient intake with colorectal cancer: A case-control study.

The risk of colorectal cancer (CRC) can be influenced by dietary components. This study aims to investigate the association between dietary intake and CRC in Iranian adults. This hospital-based case-control study was performed on 160 patients with CRC and 320 healthy people. General and pathological data were collected through face-to-face interviews. A validated food frequency questionnaire (FFQ) was used to assess the intake of calories, macronutrients, and micronutrients. The case group had a significantly higher intake of calories, carbohydrates, vitamin A, vitamin K, fluoride, and molybdenum and a lower intake of vitamin E, vitamin B1, beta carotene, biotin, folate, magnesium, selenium, manganese, and fiber (all p < .001). CRC was positively associated with the intake of carbohydrate (OR: 1.01, CI% 1.03-1.01, p = .001), and vitamin A (OR: 1.009, CI 95% 1.006-1.01, p = .001) and negatively associated with intake of fiber (OR: 0.67, CI 95% 0.59-0.76, p = .001), beta carotene (OR: 0.99, CI 95% 0.99-0.99, p = .001), vitamin E (OR: 0.27, CI 95% 0.15-0.47, p = .001), folate (OR: 0.98 CI 95% 0.97-0.98, p = .001), and biotin (OR: 0.83, CI 95% 0.77-0.90, p = .001). The associations remained significant after adjusting for age and sex. Further adjustments for physical activity, alcohol consumption, and smoking did not change the results. The results identified that the risk of colorectal cancer can be influenced by dietary intake. Further longitudinal studies are needed to confirm these findings and to identify the underlying mechanisms of the effects of dietary components on the risk of colorectal cancer.

MODA: an efficient algorithm for network motif discovery in biological networks.

In recent years, interest has been growing in the study of complex networks. Since Erdös and Rényi (1960) proposed their random graph model about 50 years ago, many researchers have investigated and shaped this field. Many indicators have been proposed to assess the global features of networks. Recently, an active research area has developed in studying local features named motifs as the building blocks of networks. Unfortunately, network motif discovery is a computationally hard problem and finding rather large motifs (larger than 8 nodes) by means of current algorithms is impractical as it demands too much computational effort. In this paper, we present a new algorithm (MODA) that incorporates techniques such as a pattern growth approach for extracting larger motifs efficiently. We have tested our algorithm and found it able to identify larger motifs with more than 8 nodes more efficiently than most of the current state-of-the-art motif discovery algorithms. While most of the algorithms rely on induced subgraphs as motifs of the networks, MODA is able to extract both induced and non-induced subgraphs simultaneously. The MODA source code is freely available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

Memory and relatedness of transcriptional activity in mammalian cell lineages.

Phenotypically identical mammalian cells often display considerable variability in transcript levels of individual genes. How transcriptional activity propagates in cell lineages, and how this varies across genes is poorly understood. Here we combine live-cell imaging of short-lived transcriptional reporters in mouse embryonic stem cells with mathematical modelling to quantify the propagation of transcriptional activity over time and across cell generations in phenotypically homogenous cells. In sister cells we find mean transcriptional activity to be strongly correlated and transcriptional dynamics tend to be synchronous; both features control how quickly transcriptional levels in sister cells diverge in a gene-specific manner. Moreover, mean transcriptional activity is transmitted from mother to daughter cells, leading to multi-generational transcriptional memory and causing inter-family heterogeneity in gene expression.

Survey and mapping of heavy metals in groundwater resources around the region of the Anzali International Wetland; a dataset.

The purpose of this study is zoning and determining the concentration of heavy metals including Arsenic (As), Mercury (Hg), Lead (Pb), and Cadmium (Cd) in the groundwater resources of villages located around the Anzali International Wetland. The amount of heavy metals (As, Hg, Pb, and Cd) in the collected samples were determined by the Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) technique. The maximum concentrations of As, Hg, Pb and Cd were 0.216, 0.059, 0.090 and 0.006 mg/L, respectively.

Physicochemical Characteristics of Larval Habitat Waters of Mosquitoes (Diptera: Culicidae) in Qom Province, Central Iran.

BACKGROUND: Mosquitoes lay eggs in a wide range of habitats with different physicochemical parameters. Ecological data, including physicochemical factors of oviposition sites, play an important role in integrated vector management. Those data help the managers to make the best decision in controlling the aquatic stages of vectors especially using source reduction. METHODS: To study some physicochemical characteristics of larval habitat waters, an investigation was carried out in Qom Province, central Iran, during spring and summer 2008 and 2009. Water samples were collected during larval collection from ten localities. The chemical parameters of water samples were analyzed based on mg/l using standard methods. Water temperature (°C), turbidity (NTU), total dissolved solids (ppm), electrical conductivity (µS/cm), and acidity (pH) were measured using digital testers. Thermotolerant coliforms of water samples were analyzed based on MPN/100ml. Data were assessed by Kruskal-Wallis test and Spearman Correlation analysis. RESULTS: In total, 371 mosquito larvae were collected including 14 species representing four genera. Some physicochemical parameters of water in Emamzadeh Esmail, Qomrood, Qom City, and Rahjerd showed significant differences among localities (P< 0.05). The physicochemical and microbial parameters did not show any significant differences among different species (P> 0.05). There was no significant correlation between the abundance of larvae and the different physicochemical and microbial parameters (P> 0.05). CONCLUSION: The means of EC, TDS, and phosphate of localities and species were remarkably higher than those of the previous studies. Other parameters seem to be in the range of other investigations.

The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.

The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, eg, by coactivating the estrogen-related receptor-α (ERRα) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these 2 proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERRα to DNA in a skeletal muscle cell line with elevated PGC-1α and linked the DNA recruitment to global PGC-1α target gene regulation. We found that, surprisingly, ERRα coactivation by PGC-1α is only observed in the minority of all PGC-1α recruitment sites. Nevertheless, a majority of PGC-1α target gene expression is dependent on ERRα. Intriguingly, the interaction between these 2 proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat-binding site configuration for ERRα, and adjacent recruitment of the transcription factor specificity protein 1. These findings thus not only reveal a novel insight into the regulatory network underlying muscle cell plasticity but also strongly link the genomic context of DNA-response elements to control transcription factor-coregulator interactions.