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, a large inversion and a retrotransposon insertion, which were not seen in 33 controls. Although we considered that they are benign SVs, this finding suggests that our pipeline using long-read WGS is useful for investigating various types of potentially pathogenic SVs. In conclusion, we identified a 97-kb deletion, which causes haploinsufficiency of MBD5 in a patient with neurodevelopmental disorder, demonstrating that long-read WGS is a powerful technique to discover pathogenic SVs.Western Kazakhstan is populated by three clans totaling 2 million people. Since the clans are patrilineal, the Y-chromosome is the most informative genetic system for tracing their origin. We genotyped 40 Y-SNP and 17 Y-STR markers in 330 Western Kazakhs. High phylogenetic resolution within haplogroup C2a1a2-M48 was achieved by using additional SNPs. Three lines of evidence indicate that the Alimuly and Baiuly clans (but not the Zhetiru clan) have a common founder placed 700 ± 200 years back by the STR data and 500 ± 200 years back by the sequencing data. This supports traditional genealogy claims about the descent of these clans from Emir Alau, who lived 650 years ago and whose lineage might be carried by two-thirds of Western Kazakhs. There is accumulation of specific haplogroups in the subclans representing other lineages, confirming that the clan structure corresponds with the paternal genetic structure of the steppe population.We present a new methodology for measuring few-femtosecond electronic and nuclear dynamics in both atoms and polyatomic molecules using multidimensional high harmonic generation (HHG) spectroscopy measurements, in which the spectra are recorded as a function of the laser intensity to form a two-dimensional data set. The method is applied to xenon atoms and to benzene molecules, the latter exhibiting significant fast nuclear dynamics following ionization. We uncover the signature of the sub-cycle evolution of the returning electron flux in strong-field ionized xenon atoms, implicit in the strong field approximation but not previously observed directly. We furthermore extract the nuclear autocorrelation function in strong field ionized benzene cations, which is determined to have a decay of [Formula see text] fs, in good agreement with the [Formula see text] fs obtained from direct dynamics variational multi-configuration Gaussian calculations. Our method requires minimal assumptions about the system, and is applicable even to un-aligned polyatomic molecules.We report an experimental demonstration of positive-negative sub-wavelength interference without correlation. Typically, people can achieve sub-wavelength effects with correlation measurement no matter by using bi-photon or thermal light sources. In this paper, we adopt a thermal light source, and we count the realizations in which the intensities of the definite symmetric points are above or below a certain threshold. The distribution of numbers of these realizations which meet the restriction will show a sub-wavelength effect. With proper constrictions, positive and negative interference patterns are demonstrated.A deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.During sporulation Bacillus subtilis Mfd couples transcription to nucleotide excision repair (NER) to eliminate DNA distorting lesions. Here, we report a significant decline in sporulation following Mfd disruption, which was manifested in the absence of external DNA-damage suggesting that spontaneous lesions activate the function of Mfd for an efficient sporogenesis. Accordingly, a dramatic decline in sporulation efficiency took place in a B. subtilis strain lacking Mfd and the repair/prevention guanine oxidized (GO) system (hereafter, the ∆GO system), composed by YtkD, MutM and MutY. Furthermore, the simultaneous absence of Mfd and the GO system, (i) sensitized sporulating cells to H2O2, and (ii) elicited spontaneous and oxygen radical-induced rifampin-resistance (Rifr) mutagenesis. Epifluorescence (EF), confocal and transmission electron (TEM) microscopy analyses, showed a decreased ability of ∆GO ∆mfd strain to sporulate and to develop the typical morphologies of sporulating cells. Remarkably, disruption of sda, sirA and disA partially, restored the sporulation efficiency of the strain deficient for Mfd and the ∆GO system; complete restoration occurred in the RecA- background. Overall, our results unveil a novel Mfd mechanism of transcription-coupled-repair (TCR) elicited by 8-OxoG which converges in the activation of a RecA-dependent checkpoint event that control the onset of sporulation in B. subtilis.While the androgen receptor (AR) may influence the progression of clear cell renal cell carcinoma (ccRCC), its role to impact vasculogenic mimicry (VM) to alter the ccRCC progression and metastasis remains obscure. Here, we demonstrated that elevated AR expression was positively correlated with tumor-originated vasculogenesis in ccRCC patients. Consistently, in vitro research revealed AR promoted VM formation in ccRCC cell lines via modulating lncRNA-TANAR/TWIST1 signals. Mechanism dissection showed that AR could increase lncRNA-TANAR (TANAR) expression through binding to the androgen response elements (AREs) located in its promoter region. Moreover, we found that TANAR could impede nonsense-mediated mRNA decay (NMD) of TWIST1 mRNA by direct interaction with TWIST1 5'UTR. A preclinical study using in vivo mouse model with orthotopic xenografts of ccRCC cells further confirmed the in vitro data. Together, these results illustrated that AR-mediated TANAR signals might play a crucial role in ccRCC VM formation and metastasis, and targeting this newly identified AR/TANAR/TWIST1 signaling may help in the development of a novel anti-angiogenesis therapy to better suppress the ccRCC progression.Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of "size" (number of edges and minimum vertex cover) of the JAK/STAT network with treatment effect in rheumatoid arthritis (RA), phenotype of viral infection and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK/STAT pathway Measles, Influenza A, West Nile virus, Japanese B virus, Yellow Fever virus, respiratory syncytial virus, Kaposi's sarcoma virus, Hepatitis B and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho = - 0.815, R2 = 0.676, p = 0.007, for vertex cover rho = - 0.793, R2 = 0.635, p = 0.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections. In the JAK/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection.Identifying distinct normal extracellular matrix (ECM) features from pathology is of the upmost clinical importance for laryngeal diagnostics and therapy. Despite remarkable histological contributions, our understanding of the vocal fold (VF) physiology remains murky. The emerging field of non-invasive 3D optical imaging may be well-suited to unravel the complexity of the VF microanatomy. This study focused on characterizing the entire VF ECM in length and depth with optical imaging. A quantitative morphometric evaluation of the human vocal fold lamina propria using two-photon excitation fluorescence (TPEF), second harmonic generation (SHG), and optical coherence tomography (OCT) was investigated. Fibrillar morphological features, such as fiber diameter, orientation, anisotropy, waviness and second-order statistics features were evaluated and compared according to their spatial distribution. The evidence acquired in this study suggests that the VF ECM is not a strict discrete three-layer structure as traditionally described but instead a continuous assembly of different fibrillar arrangement anchored by predominant collagen transitions zones. We demonstrated that the ECM composition is distinct and markedly thinned in the anterior one-third of itself, which may play a role in the development of some laryngeal diseases. We further examined and extracted the relationship between OCT and multiphoton imaging, promoting correspondences that could lead to accurate 3D mapping of the VF architecture in real-time during phonosurgeries. As miniaturization of optical probes is consistently improving, a clinical translation of OCT imaging and multiphoton imaging, with valuable qualitative and quantitative features, may have significant implications for treating voice disorders.Idiopathic pulmonary fibrosis (IPF) is an independent risk factor for lung cancer (LC) development; however, there are currently no clinical guidelines for LC surveillance in IPF. This study aimed to investigate the cumulative incidence and survival outcomes of LC in IPF. Using the National Health Insurance Service database, including medical information on people aged ≥ 40 years between 2011 and 2016, we identified IPF patients and confirmed the presence of comorbid LC. Patients diagnosed with IPF in 2011 were washed out, and mortality data were analyzed from 2012 to 2018. A total of 7277 newly diagnosed IPF patients were identified among Korean citizens aged ≥ 40 years (about 50 million people) between 2011 and 2016. XMU-MP-1 nmr Their average age was 71.5 years and 72.8% of them were male. The prevalence of LC in the IPF cases was 6.4%. The cumulative incidence rates of LC in IPF patients who did not have LC at the time of IPF diagnosis were 1.7%, 4.7%, and 7.0%, at 1, 3, and 5 years, respectively. The median time from IPF diagnosis to LC development was 16.
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