Molecular characterization of a mosaic locus in the genome of 'Candidatus Liberibacter asiaticus'

<p>Abstract</p> <p>Background</p> <p>Huanglongbing (HLB) is a highly destructive disease of citrus production worldwide. '<it>Candidatus </it>Liberibacter asiaticus', an unculturable alpha proteobacterium, is a putative pathogen of HLB. Information about the biology and strain diversity of '<it>Ca</it>. L. asiaticus' is currently limited, inhibiting the scope of HLB research and control.</p> <p>Results</p> <p>A genomic region (CLIBASIA_05640 to CLIBASIA_05650) of '<it>Ca</it>. L. asiaticus' showing hyper-sequence variation or locus mosaicism was identified and investigated using 262 bacterial strains (188 from China and 74 from Florida). Based on the characteristic electrophoretic profiles of PCR amplicons generated by a specific primer set, eight electrophoretic types (E-types) were identified, six E-types (A, B, C, D, E, and F) in China and four E-types (A, C, G, and H) in Florida. The '<it>Ca</it>. L. asiaticus' strains from China consisted predominately of E-type A (71.3%) and E-type B (19.7%). In contrast, the '<it>Ca</it>. L. asiaticus' strains from Florida was predominated by E-type G (82.4%). Diversity of '<it>Ca</it>. L. asiaticus' in China was also evidenced. Strains from the high altitude Yunnan Province consisted of five E-types with E-type B being the majority (62.8%), whereas strains from the low altitude coastal Guangdong Province consisted of only two E-types with E-type A as the majority (97.0%). Sequence analyses revealed that variation of DNA amplicons was due to insertion/deletion events at CLIBASIA_05650 and the downstream intergenic region.</p> <p>Conclusions</p> <p>This study demonstrated the genomic mosaicism of '<it>Ca</it>. L. asiaticus' resulted from active DNA insertion/deletion activities. Analyses of strain variation depicted the significant inter- and intra-continent diversity of '<it>Ca</it>. L. asiaticus'.</p

The human parvovirus B19 non-structural protein 1 N-terminal domain specifically binds to the origin of replication in the viral DNA

The non-structural protein 1 (NS1) of human parvovirus B19 plays a critical role in viral DNA replication. Previous studies identified the origin of replication in the viral DNA, which contains four DNA elements, namely NSBE1 to NSBE4, that are required for optimal viral replication (Guan et al, 2009, J. Virology, 83, 9541-9553). Here we have demonstrated in vitro that the NS1 N-terminal domain (NS1N) binds to the origin of replication in a sequence-specific, length-dependent manner that requires NSBE1 and NSBE2, while NSBE3 and NSBE4 are dispensable. Mutagenesis analysis has identified nucleotides in NSBE1 and NSBE2 that are critical for NS1N binding. These results suggest that NS1 binds to the NSBE1-NSBE2 region in the origin of replication, while NSBE3 and NSBE4 may provide binding sites for potential cellular factors. Such a specialized nucleoprotein complex may enable NS1 to nick the terminal resolution site and separate DNA strands during replication

The human parvovirus B19 non-structural protein 1 N-terminal domain specifically binds to the origin of replication in the viral DNA

The non-structural protein 1 (NS1) of human parvovirus B19 plays a critical role in viral DNA replication. Previous studies identified the origin of replication in the viral DNA, which contains four DNA elements, namely NSBE1 to NSBE4, that are required for optimal viral replication (Guan et al, 2009, J. Virology, 83, 9541-9553). Here we have demonstrated in vitro that the NS1 N-terminal domain (NS1N) binds to the origin of replication in a sequence-specific, length-dependent manner that requires NSBE1 and NSBE2, while NSBE3 and NSBE4 are dispensable. Mutagenesis analysis has identified nucleotides in NSBE1 and NSBE2 that are critical for NS1N binding. These results suggest that NS1 binds to the NSBE1-NSBE2 region in the origin of replication, while NSBE3 and NSBE4 may provide binding sites for potential cellular factors. Such a specialized nucleoprotein complex may enable NS1 to nick the terminal resolution site and separate DNA strands during replication

3D Stretchable Arch Ribbon Array Fabricated via Grayscale Lithography.

Microstructures with flexible and stretchable properties display tremendous potential applications including integrated systems, wearable devices and bio-sensor electronics. Hence, it is essential to develop an effective method for fabricating curvilinear and flexural microstructures. Despite significant advances in 2D stretchable inorganic structures, large scale fabrication of unique 3D microstructures at a low cost remains challenging. Here, we demonstrate that the 3D microstructures can be achieved by grayscale lithography to produce a curved photoresist (PR) template, where the PR acts as sacrificial layer to form wavelike arched structures. Using plasma-enhanced chemical vapor deposition (PECVD) process at low temperature, the curved PR topography can be transferred to the silicon dioxide layer. Subsequently, plasma etching can be used to fabricate the arched stripe arrays. The wavelike silicon dioxide arch microstructure exhibits Young modulus and fracture strength of 52 GPa and 300 MPa, respectively. The model of stress distribution inside the microstructure was also established, which compares well with the experimental results. This approach of fabricating a wavelike arch structure may become a promising route to produce a variety of stretchable sensors, actuators and circuits, thus providing unique opportunities for emerging classes of robust 3D integrated systems

Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways

Human bocavirus 1 (HBoV1) belongs to the genus Bocaparvovirus of the Parvoviridae family, and is an emerging human pathogenic respiratory virus. In vitro, HBoV1 infects well-differentiated/polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). Although it is well known that autonomous parvovirus replication depends on the S phase of the host cells, we demonstrate here that the HBoV1 genome amplifies efficiently in mitotically quiescent airway epithelial cells of HAE-ALI cultures. Analysis of HBoV1 DNA in infected HAE-ALI revealed that HBoV1 amplifies its ssDNA genome following a typical parvovirus rolling-hairpin DNA replication mechanism. Notably, HBoV1 infection of HAE-ALI initiates a DNA damage response (DDR) with activation of all three phosphatidylinositol 3-kinase–related kinases (PI3KKs). We found that the activation of the three PI3KKs is required for HBoV1 genome amplification; and, more importantly, we identified that two Y-family DNA polymerases, Pol η and Pol κ, are involved in HBoV1 genome amplification. Overall, we have provided an example of de novo DNA synthesis (genome amplification) of an autonomous parvovirus in non-dividing cells, which is dependent on the cellular DNA damage and repair pathways

Mobility-Aware Joint User Scheduling and Resource Allocation for Low Latency Federated Learning

As an efficient distributed machine learning approach, Federated learning (FL) can obtain a shared model by iterative local model training at the user side and global model aggregating at the central server side, thereby protecting privacy of users. Mobile users in FL systems typically communicate with base stations (BSs) via wireless channels, where training performance could be degraded due to unreliable access caused by user mobility. However, existing work only investigates a static scenario or random initialization of user locations, which fail to capture mobility in real-world networks. To tackle this issue, we propose a practical model for user mobility in FL across multiple BSs, and develop a user scheduling and resource allocation method to minimize the training delay with constrained communication resources. Specifically, we first formulate an optimization problem with user mobility that jointly considers user selection, BS assignment to users, and bandwidth allocation to minimize the latency in each communication round. This optimization problem turned out to be NP-hard and we proposed a delay-aware greedy search algorithm (DAGSA) to solve it. Simulation results show that the proposed algorithm achieves better performance than the state-of-the-art baselines and a certain level of user mobility could improve training performance

Specifying cycles of minimal length for commonly used linear layers in block ciphers

With the advances of Internet-of-Things (IoT) applications in smart cities and the pervasiveness of network devices with limited resources, lightweight block ciphers have achieved rapid development recently. Due to their relatively simple key schedule, nonlinear invariant attacks have been successfully applied to several families of lightweight block ciphers. This attack relies on the existence of a nonlinear invariant g:\F_2^n \rightarrow \F_2 for the round function $F_k$ so that $g(x) + g(F_k(x))$ is constant for any input value $x$. Whereas invariants of the entire $S$-box layer has been studied in terms of the corresponding cycle structure [TLS16,WRP20] (assuming the use of bijective S-boxes), a similar analysis for the linear layer has not been performed yet. In this article, we provide a theoretical analysis for specifying the minimal length of cycles for commonly used linear permutations (implementing linear layers) in lightweight block ciphers. Namely, using a suitable matrix representation, we exactly specify the minimal cycle lengths for those (efficiently implemented) linear layers that employ ShiftRows, Rotational-XOR and circular Boolean matrix operations which can be found in many well-known families of block ciphers. These results are practically useful for the purpose of finding nonlinear invariants of the entire encryption rounds since these can be specified using the intersection of cycles corresponding to the linear and S-box layer. We also apply our theoretical analysis practically and specify minimal cycle lengths of linear layers for certain families of block ciphers including some NIST candidates

The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress

Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail.Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated.Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways.Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy