Animal models for human genetic diseases

The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to model and understand disease and to test new systems of treating disease. The range of model organisms is large, extending from microbes to primates. Mice are widely considered to be the prime model of genetic human disease. In this review, we will mainly focus on the mouse, which is the mammalian species with the best studied genetics.Key words: Animal models, mice, genetic diseases

Sorptive Interactions Evaluation of Benomyl Metabolites Mecarzole with the Varyingly Selected Minerals

Soil and soil minerals are the primary recipients of different contaminates coming in immediate contact.Agricultural practices which are dominated by use of different agrochemicals have further aggravated the soil quality.Fungicides, aimed at the extermination, inhibition and growth retardation of fungal species in agricultural crops havebeen used frequently. Among such fungicides, Benzimidazole based fungicides are of prime significance due to theircomparatively improved annihilatory activity. Despite such frequent utilization, the reports on the reception andconsequent sorption of Benzimidazole fungicides are scarce. Current work has, for the first time, investigated theinteraction of Benzimidazole based fungicide, Mecarzole (metabolite of Benomyl fungicide and also known asCarbendazim) in the selected minerals i.e. corundum (alumina), silica, muscovite and montmorillonite. The interactionwas studied via standard equilibration method established in batches. Adsorption and desorption of Mecarzole in theselected minerals was evaluated by multilayer Linear and Freundlich model for different parameters i.e. Kd, Kf, Kfdesand Kdes. Linearity was exhibited by the minerals for attachment of Mecarzole. The highest values of Kd (6.93 mL. µg-1) and Kf (7.99 mL. µg-1) obtained for muscovite are indicative of the higher affinity of muscovite for Mecarzole incomparison to other three minerals. Excellent adsorption of Mecarzole in muscovite is suggestive of the fact thatMecarzole interacting with muscovite is not a threat towards lower soil profiles since there is a stronger bonding. Incontrast to muscovite, Mecarzole poorly adsorbed in alumina represents a threat to soils due to possible percolation ofpoorly adsorbed Mecarzole molecules

Image Enhancement and Segmentation Techniques for Detection of Knee Joint Diseases: A Survey

Knee bone diseases are rare but might be highly destructive. Magnetic resonance imaging (MRI) is the main approach to identify knee cancer and its treatment. Normally, the knee cancers are pointed out with the help of different MRI analysis techniques and latter image analysis strategies understand these images. Computer-based medical image analysis is getting researcher's interest due to its advantages of speed and accuracy as compared to traditional techniques. The focus of current research is MRI-based medical image analysis for knee bone disease detection. Accordingly, several approaches for features extraction and segmentation for knee bone cancer are analyzed and compared on benchmark database. Finally, the current state of the art is investigated and future directions are proposed

The asymmetric effect of public private partnership investment on transport CO2 emission in China: Evidence from quantile ARDL approach

Transportation infrastructure is a pillar of economic development as well as a main contributor to climate change. Therefore, it is necessary to transform the transport sector investment into climate-resilient, low-carbon transportation choices in order to achieve sustainable transportation infrastructure. In case of China, this transformation might be necessary from the perspective of the “New-style Urbanization” strategy, and for fulfilling this strategy, policy realignment is required. To address this policy-level void in the literature, we explore the influence of public private partnerships investment in transport sector, renewable energy consumption, urbanization on transport-induced carbon emissions in China. For this purpose, we apply Quantile Autoregressive Distributed Lagged (QARDL) method during 1990Q1-2018Q4. Based on the results of the study, a multipronged sustainable development goal (SDG) framework has been suggested, under which SDG 11, SDG 13, and SDG 8 are addressed, while using SDG 17 as a vehicle

Assembly of Smart Microgels and Hybrid Microgels on Graphene Sheets for Catalytic Reduction of Nitroarenes

Poly (N-isopropylacrylamide-acrylic acid) [p(NIPAM-AAc)] microgel was successfully fabricated using the precipitation polymerization method. Silver (Ag) nanoparticles and graphene oxide (G) were used to fabricate the following hybrid microgels: Ag-p(NIPAM-AAc) (Ag-HMG), Ag-G-p(NIPAM-AAc) (Ag-G-HMG), and G-p(NIPAM-AAc) (G-HMG). Ag-HMG, Ag-G-HMG, and G-HMG were characterized using a Zetasizer and UV-Vis spectroscopy. The reduction of a series of different compounds with comparable and distinct chemical structures was catalyzed by synthesized Ag-HMG, Ag-G-HMG, and G-HMG hybrid microgels. The average size of Ag nanoparticles was found to be ~50 nm. Ag nanoparticles were synthesized within microgels attached to G sheets. Ag-p(NIPAM-AAc), Ag-G-p(NIPAM-AAc), and G-p(NIPAM-AAc) hybrid microgels were used for the catalytic reduction of nitroarenes and dyes. By comparing their apparent rate constant (kapp), reduction duration, and percentage reduction, the activity of HMG (hybrid microgel) as a catalyst towards different substrates was investigated. Graphene sheets play role in electron relay among Ag nanoparticles and microgels.publishedVersio

Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature

Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype‐up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrom

In Silico Bioinformatics Followed by Molecular Validation Using Archival FFPE Tissue Biopsies Identifies a Panel of Transcripts Associated with Severe Asthma and Lung Cancer

Severe asthma and lung cancer are both heterogeneous pathological diseases affecting the lung tissue. Whilst there are a few studies that suggest an association between asthma and lung cancer, to the best of our knowledge, this is the first study to identify common genes involved in both severe asthma and lung cancer. Publicly available transcriptomic data for 23 epithelial brushings from severe asthmatics and 55 samples of formalin-fixed paraffin-embedded (FFPE) lung cancer tissue at relatively early stages were analyzed by absolute gene set enrichment analysis (GSEA) in comparison to 37 healthy bronchial tissue samples. The key pathways enriched in asthmatic patients included adhesion, extracellular matrix, and epithelial cell proliferation, which contribute to tissue remodeling. In the lung cancer dataset, the main pathways identified were receptor tyrosine kinase signaling, wound healing, and growth factor response, representing the early cancer pathways. Analysis of the enriched genes derived from the pathway analysis identified seven genes expressed in both the asthma and lung cancer sets: BCL3, POSTN, PPARD, STAT1, MYC, CD44, and FOSB. The differential expression of these genes was validated in vitro in the cell lines retrieved from different lung cancer and severe asthma patients using real-time PCR. The effect of the expression of the seven genes identified in the study on the overall survival of lung cancer patients (n = 1925) was assessed using a Kaplan–Meier plot. In vivo validation performed in the archival biopsies obtained from patients diagnosed with both the disease conditions provided interesting insights into the pathogenesis of severe asthma and lung cancer, as indicated by the differential expression pattern of the seven transcripts in the mixed group as compared to the asthmatics and lung cancer samples alone

IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans

Motile and non-motile cilia play critical roles in mammalian development and health. These organelles are composed of a 1000 or more unique proteins, but their assembly depends entirely on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). In mammals, malfunction of non-motile cilia due to IFT dysfunction results in complex developmental phenotypes that affect most organs. In contrast, disruption of motile cilia function causes subfertility, disruption of the left-right body axis, and recurrent airway infections with progressive lung damage. In this work, we characterize allele specific phenotypes resulting from IFT74 dysfunction in human and mice. We identified two families carrying a deletion encompassing IFT74 exon 2, the first coding exon, resulting in a protein lacking the first 40 amino acids and two individuals carrying biallelic splice site mutations. Homozygous exon 2 deletion cases presented a ciliary chondrodysplasia with narrow thorax and progressive growth retardation along with a mucociliary clearance disorder phenotype with severely shorted cilia. Splice site variants resulted in a lethal skeletal chondrodysplasia phenotype. In mice, removal of the first 40 amino acids likewise results in a motile cilia phenotype but with little effect on primary cilia structure. Mice carrying this allele are born alive but are growth restricted and developed hydrocephaly in the first month of life. In contrast, a strong, likely null, allele of Ift74 in mouse completely blocks ciliary assembly and causes severe heart defects and midgestational lethality. In vitro studies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia resulting from increased mechanical stress and repair needs could account for the motile cilia phenotype observed in human and mice