Cerebral Infarction in an Elderly Patient with Coronavirus Disease

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Whole Genome Sequence of a Turkish Individual

Although whole human genome sequencing can be done with readily available technical and financial resources, the need for detailed analyses of genomes of certain populations still exists. Here we present, for the first time, sequencing and analysis of a Turkish human genome. We have performed 35x coverage using paired-end sequencing, where over 95% of sequencing reads are mapped to the reference genome covering more than 99% of the bases. The assembly of unmapped reads rendered 11,654 contigs, 2,168 of which did not reveal any homology to known sequences, resulting in,1 Mbp of unmapped sequence. Single nucleotide polymorphism (SNP) discovery resulted in 3,537,794 SNP calls with 29,184 SNPs identified in coding regions, where 106 were nonsense and 259 were categorized as having a high-impact effect. The homo/ hetero zygosity (1,415,123:2,122,671 or 1:1.5) and transition/transversion ratios (2,383,204:1,154,590 or 2.06:1) were within expected limits. Of the identified SNPs, 480,396 were potentially novel with 2,925 in coding regions, including 48 nonsense and 95 high-impact SNPs. Functional analysis of novel high-impact SNPs revealed various interaction networks, notably involving hereditary and neurological disorders or diseases. Assembly results indicated 713,640 indels (1:1.09 insertion/ deletion ratio), ranging from 252 bp to 34 bp in length and causing about 180 codon insertion/deletions and 246 frame shifts. Using paired-end- and read-depth-based methods, we discovered 9,109 structural variants and compared our variant findings with other populations. Our results suggest that whole genome sequencing is a valuable tool for understanding variations in the human genome across different populations. Detailed analyses of genomes of diverse origins greatly benefits research in genetics and medicine and should be conducted on a larger scale

Synthesis and Characterization of Some 2-Azetidinones and Unexpected Azet-2(1H)-ones

2-Azetidinone (2b–e) and some unexpected azet-2(1H)-one derivatives (3b–f) were synthesized in two steps from the substitution of 2-aminobenzothiazole and different substituted aromatic aldehydes. Firstly, the Schiff bases were prepared via reaction of different 2-aminobenzothiazoles with different aromatic aldehydes. Second step was the formation of corresponding 2-azetidinone and some unexpected azet-2(1H)-one analogues by cyclocondensation of the Schiff bases with chloroacetyl chloride and phenoxy acetyl chloride in the presence of triethylamine. The chemical structures of the newly synthesized compounds were confirmed by FTIR, 1H NMR, 13C NMR, HMQC, elemental analysis and mass spectroscopic analysis. This work is licensed under a Creative Commons Attribution 4.0 International License

Comparative analysis of single-cell transcriptomics in human and Zebrafish oocytes

Background: Zebrafish is a popular model organism, which is widely used in developmental biology research. Despite its general use, the direct comparison of the zebrafish and human oocyte transcriptomes has not been well studied. It is significant to see if the similarity observed between the two organisms at the gene sequence level is also observed at the expression level in key cell types such as the oocyte. Results: We performed single-cell RNA-seq of the zebrafish oocyte and compared it with two studies that have performed single-cell RNA-seq of the human oocyte. We carried out a comparative analysis of genes expressed in the oocyte and genes highly expressed in the oocyte across the three studies. Overall, we found high consistency between the human studies and high concordance in expression for the orthologous genes in the two organisms. According to the Ensembl database, about 60% of the human protein coding genes are orthologous to the zebrafish genes. Our results showed that a higher percentage of the genes that are highly expressed in both organisms show orthology compared to the lower expressed genes. Systems biology analysis of the genes highly expressed in the three studies showed significant overlap of the enriched pathways and GO terms. Moreover, orthologous genes that are commonly overexpressed in both organisms were involved in biological mechanisms that are functionally essential to the oocyte. Conclusions: Orthologous genes are concurrently highly expressed in the oocytes of the two organisms and these genes belong to similar functional categories. Our results provide evidence that zebrafish could serve as a valid model organism to study the oocyte with direct implications in human

Proteomic Identification of Interleukin-2 Therapy Response in Metastatic Renal Cell Cancer

Introduction—To detect a predictive protein profile that distinguishes between IL-2 therapy responders and non-responders among metastatic RCC patients we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). Materials and Methods—Protein extracts of 56 metastatic clear cell RCC patients obtained from radical nephrectomy specimens and prior to IL-2 therapy were applied to protein chip arrays of different chromatographic properties and analyzed using SELDI TOF-MS. A class prediction algorithm was applied to identify a subset of protein peaks whose expression values were associated with IL-2 response status. Multivariate analysis was performed to assess the association between the proteomic profile and the IL-2 response status controlling for the effect of lymphadenopathy. Results—From a total of 513 protein peaks we discovered a predictor set of 11 peaks that performed optimally for predicting IL-2 response status (86 % accuracy, Fisher’s p\u3c0.004, permutation p\u3c0.01). The results were validated on an independent data set with an overall accuracy of 72% (p \u3c 0.05, permutation p\u3c0.01). On multivariate analysis the proteomic profile was significantly associated with IL-2 response when corrected for lymph node status (p\u3c 0.04). Conclusions—We have identified and validated a proteomic pattern that is an independent predictor of IL-2 response. The ability to predict the probability of IL-2 response could permit targeted selection of patients most likely to respond to IL-2, while avoiding unwanted toxicities in patients less likely to respond. This proteomic predictor has the potential to significantly aid clinicians in the decision making of appropriate therapy for metastatic RCC patients

Serum Protein Signatures Using Aptamer-Based Proteomics for Minimal Change Disease and Membranous Nephropathy

Introduction: Minimal change disease (MCD) and membranous nephropathy (MN) are glomerular diseases (glomerulonephritis [GN]) that present with the nephrotic syndrome. Although circulating PLA2R antibodies have been validated as a biomarker for MN, the diagnosis of MCD and PLA2R-negative MN still relies on the results of kidney biopsy or empirical corticosteroids in children. We aimed to identify serum protein biomarker signatures associated with MCD and MN pathogenesis using aptamer-based proteomics. Methods: Quantitative SOMAscan proteomics was applied to the serum of adult patients with MCD (n = 15) and MN(n = 37) and healthy controls (n = 20). Associations between the 1305proteins detected with SOMAscan were assessed using multiple statistical tests, expression pattern analysis, and systems biology analysis. Results: A total of 208 and 244 proteins were identified that differentiated MCD and MN, respectively, with high statistical significance from the healthy controls (Benjamin-Hochberg [BH] P \u3c 0.0001). There were 157 proteins that discriminated MN from MCD (BH P \u3c 0.05). In MCD, 65 proteins were differentially expressed as compared with MN and healthy controls. When compared with MCD and healthy controls, 44 discriminatory proteins were specifically linked to MN. Systems biology analysis of these signatures identified cell death and inflammation as key pathways differentiating MN from MCD and healthy controls. Dysregulation of fatty acid metabolism pathways was confirmed in both MN and MCD as compared with the healthy subjects. Conclusion: SOMAscan represents a promising proteomic platform for biomarker development in GN. Validation of a greater number of discovery biomarkers in larger patient cohorts is needed before these data can be translated for clinical care

Archaeogenomic analysis of the first steps of Neolithization in Anatolia and the Aegean

The Neolithic transition in west Eurasia occurred in two main steps: the gradual development of sedentism and plant cultivation in the Near East and the subsequent spread of Neolithic cultures into the Aegean and across Europe after 7000 cal BCE. Here, we use published ancient genomes to investigate gene flow events in west Eurasia during the Neolithic transition. We confirm that the Early Neolithic central Anatolians in the ninth millennium BCE were probably descendants of local hunter-gatherers, rather than immigrants from the Levant or Iran. We further study the emergence of post-7000 cal BCE north Aegean Neolithic communities. Although Aegean farmers have frequently been assumed to be colonists originating from either central Anatolia or from the Levant, our findings raise alternative possibilities: north Aegean Neolithic populations may have been the product of multiple westward migrations, including south Anatolian emigrants, or they may have been descendants of local Aegean Mesolithic groups who adopted farming. These scenarios are consistent with the diversity of material cultures among Aegean Neolithic communities and the inheritance of local forager know-how. The demographic and cultural dynamics behind the earliest spread of Neolithic culture in the Aegean could therefore be distinct from the subsequent Neolithization of mainland Europe.WoSScopu

Characteristics of food allergy in children: National multicenter study

Conference: Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) Location: Lisbon, PORTUGAL Date: JUN 01-05, 2019Background : Food allergies impose a significant burden on the life of the child and the family. In this study, to determine the demographic characteristics of food allergies, we investigated the characteristics of patients with food allergies in different regions of Pediatric Allergy- Immunology departments in Turkey. Method : Turkey ' s National Study of Allergy and Clinical Immunology Society has conducted a Study Group on Food Allergies. 25 centers participated in this multicenter, cross- sectional and descriptive study.European Academy of Allergy and Clinical Immunolog