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Abstract Background B cell affinity maturation enables B cells to generate high-affinity antibodies. This process involves somatic hypermutation of B cell immunoglobulin receptor (BCR) genes and selection by their ability to bind antigens. Lineage trees are used to describe this microevolution of B cell immunoglobulin genes. In a lineage tree, each node is one BCR sequence that mutated from the germinal center and each directed edge represents a single base mutation, insertion or deletion. In BCR sequencing data, the observed data only contains a subset of BCR sequences in this microevolution process. Therefore, reconstructing the lineage tree from experimental data requires algorithms to build the tree based on partially observed tree nodes. Results We developed a new algorithm named Grow Lineages along Minimum Spanning Tree (GLaMST), which efficiently reconstruct the lineage tree given observed BCR sequences that correspond to a subset of the tree nodes. Through comparison using simulated and real data, GLaMST outperforms existing algorithms in simulations with high rates of mutation, insertion and deletion, and generates lineage trees with smaller size and closer to ground truth according to tree features that highly correlated with selection pressure. Conclusions GLaMST outperforms state-of-art in reconstruction of the BCR lineage tree in both efficiency and accuracy. Integrating it into existing BCR sequencing analysis frameworks can significant improve lineage tree reconstruction aspect of the analysis.

Abstract Background Gene expression is complex and regulated by multiple molecular mechanisms, such as miRNA-mediated gene inhibition and alternative-splicing of pre-mRNAs. However, the coordination of interaction between miRNAs with different splicing isoforms, and the change of splicing isoform in response to different cellular environments are largely unexplored in plants. In this study, we analyzed the miRNA and mRNA transcriptome from lotus (Nelumbo nucifera), an economically important flowering plant. Results Through RNA-seq analyses on miRNAs and their target genes (isoforms) among six lotus tissues, expression of most miRNAs seem to be negatively correlated with their targets and tend to be tissue-specific. Further, our results showed that preferential interactions between miRNAs and hub gene isoforms in one coexpression module which is highly correlated with leaf. Intriguingly, for many genes, their corresponding isoforms were assigned to different co-expressed modules, and they exhibited more divergent mRNA structures including presence and absence of miRNA binding sites, suggesting functional divergence for many isoforms is escalated by both structural and expression divergence. Further detailed functional enrichment analysis of miRNA targets revealed that miRNAs are involved in the regulation of lotus growth and development by regulating plant hormone-related pathway genes. Conclusions Taken together, our comprehensive analyses of miRNA and mRNA transcriptome elucidate the coordination of interaction between miRNAs and different splicing isoforms, and highlight the functional divergence of many transcript isoforms from the same locus in lotus.

Purpose. Inflammation and apoptosis after spinal cord contusion (SCC) are important causes of irreversible spinal cord injury. Interleukin-1β (IL-1β) is a key inflammatory factor that promotes the aggravation of spinal cord contusion. However, the specific role and regulatory mechanism of IL-1β in spinal cord contusion is still unclear. Therefore, this study applied bioinformatics to analyze and mine potential gene targets interlinked with IL-1β, animal experiments and lentiviral interference technology were used to explore whether IL-1β affected the recovery of motor function in spinal cord contusion by interfering with PI3K/AKT1 signaling pathway. Method. This study used bioinformatics to screen and analyze gene targets related to IL-1β. The rat SCC animal model was established by the Allen method, and the Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the spinal cord-injured rats. Immunohistochemistry and immunofluorescence were used to localize the expression of IL-1β and AKT1 proteins in spinal cord tissue. Quantitative polymerase chain reaction and Western blot were used to detect the gene and protein expressions of IL-1β, PI3K, and AKT1. RNAi technology was used to construct lentivirus to inhibit the expression of IL-1β, lentiviral interference with IL-1β was used to investigate the effect of IL-1β and AKT1 on the function of spinal cord contusion and the relationship among IL-1β, AKT1, and downstream signaling pathways. Results. Bioinformatics analysis suggested a close relationship between IL-1β and AKT1. Animal experiments have confirmed that IL-1β is closely related to the functional recovery of spinal cord contusion. Firstly, from the phenomenological level, the BBB score decreased after SCC, IL-1β and AKT1 were located in the cytoplasm of neurons in the anterior horn of the spinal cord, and the expression levels of IL-1β gene and protein in the experimental group were higher than those in the sham operation group. At the same time, the expression of AKT1 gene decreased, the results suggested that the increase of IL-1β affected the functional recovery of spinal cord contusion. Secondly, from the functional level, after inhibiting the expression of IL-1β with a lentivirus-mediated method, the BBB score was significantly increased, and the motor function of the spinal cord was improved. Thirdly, from the mechanistic level, bioinformatics analysis revealed the relationship between IL-1β and AKT1. In addition, the experiment further verified that in the PI3K/AKT1 signaling pathway, inhibition of IL-1β expression upregulated AKT1 gene expression, but PI3K expression was unchanged. Conclusion. Inhibition of IL-1β promotes recovery of motor function after spinal cord injury in rats through upregulation of AKT1 expression in the PI3K/AKT1 signaling pathway. Bioinformatics analysis suggested that IL-1β may affect apoptosis and regeneration by inhibiting the expression of AKT1 in the PI3K/AKT1 signaling pathway to regulate the downstream FOXO, mTOR, and GSK3 signaling pathways; thereby hindering the recovery of motor function in rats after spinal cord contusion. It provided a new perspective for clinical treatment of spinal cord contusion in the future.

Objective: Autophagy influences a wide range of physiological and pathological processes in the human body. In this study, we aimed to investigate the role of autophagy in early-onset preeclampsia (EOPE); autophagy activation by hypoxia could rescue impaired angiogenesis and apoptosis in preeclampsia, leading by ox-LDL.Methods: Transmission electron microscopy was applied to identify autolysosomes in trophoblast cells of the placenta apical region. Quantitative real-time polymerase chain reaction, Western blot, flow cytometry, and wound-healing assays were adopted to determine autophagy activity, angiogenesis, and apoptosis in placenta tissues or HTR8/SVneo cells.Results: Autophagy activity was inhibited in the placenta of women who experienced EOPE; autophagy activation by hypoxia enhanced the migration ability, rescued ox-LDL–mediated impaired angiogenesis in HTR8/SVneo cells [vascular endothelial growth factor A (VEGFA) downregulation and FMS-like tyrosine kinase-1 (FLT1) upregulation], and protected against cell apoptosis (BAX downregulation).Conclusion: Autophagy could maintain the function of trophoblast cells by differentially regulating the expression of VEGFA and FLT1 and protecting against cell apoptosis at the maternal–fetal interface, potentially related to prevention of preeclampsia.

Presented in this paper is a method of bidirectional real and reactive power control of a three-phase grid-connected inverter under unbalanced grid situations. Unbalanced three-phase load and unbalanced grid impedance are illustrations of unbalanced grid issues that have been investigated. As a result, both grid currents and point-of-common-coupling (PCC) voltages will be unbalanced. The real and reactive power that is delivered to the grid oscillates by a significant amount in these unbalanced conditions. A time-domain symmetrical components extraction approach is used to calculate the inverter’s reference currents from the negative- and zero-sequence components of the measured currents. The suggested approach corrects unbalanced grid currents and unbalanced PCC voltages, and provides the desired real and reactive power to the grid when unbalanced situations exist. As a consequence, power oscillations will be eliminated, and power control will be possible. The suggested method’s performance is supported by simulation, and various experimental results are obtained utilizing the dSPACE DS1202 real-time interface platform.

Proposed in this article is bidirectional real and reactive power control of a three-phase grid-connected inverter under unbalanced grid conditions using a proportional-resonance controller. Different unbalanced grid conditions have been studied, such as unbalanced three-phase load and unbalanced grid impedance. These unbalanced scenarios generate unbalanced grid currents and unbalanced point-of-common-coupling (PCC) voltages, causing large oscillations in both real and reactive power transferred to the grid. The purposes of the suggested technique are to balance the grid currents and point-of-common-coupling voltages as well as control the power injected into the grid. As a result, balanced PCC voltages are guaranteed, the oscillation in real and reactive power is reduced, and power control is achieved. The proposed method’s performance has been verified in MATLAB/SIMULINK simulation software, and different experimental results have been obtained using a real-time interface platform, dSPACE DS1202.

Considering the system deformation, a procedure to predict the mesh behaviors for face-hobbed hypoid gear pair in car rear axle was proposed based on the tooth surface model and the finite element analysis (FEA) tooth contact model. The mathematical model of face-hobbed hypoid gear was derived based on the manufacturing process. The systematic model of the whole rear axle was developed in Masta, and the misalignments caused by system deformation of the hypoid gear pair was calculated. The impacts of the comprehensive misalignments and independent misalignments on mesh behaviors of hypoid gear were studied, respectively. Results show that the comprehensive misalignments under the rated load level have less influence on the contact characteristics. However, for the parametric studies of independent misalignment, the offset misalignment, and the gear axial misalignment have obvious influences on the contact pattern and transmission error. The peak-to-peak value for angular transmission error with the offset misalignment decreases significantly, when misalignment change from negative to positive. While that with the gear axial misalignment increases progressively. For shaft angle misalignment has an obvious impact on the location of the contact area and it causes a little increase of the peak-to-peak value for transmission error. Relatively, the pinion axial misalignment has diminutive impacts on the contact pattern and transmission error.

Taking the NW planetary gear transmission of an electric wheel hub as the research object, the mesh model was developed to calculate the mesh parameters using Masta. Then the lump parameter method was used to establish the dynamic model of the NW planetary transmission system considering the time-varying mesh stiffness, transmission error and bearing stiffness. The impacts of the torque load on the dynamic characteristics including the dynamic mesh force, center trajectory, offsets and load sharing coefficients were investigated. Results show that the dynamic mesh force waveform and spectral characteristics of each planetary gear at high and low speeds under the rated and maximum torque load are almost identical. Compared to the peak response at speed 485 rpm and 1770 rpm, both the magnitude and location of the third response at relative high speed about 4300 rpm are increased due to the load increasing. The mean and fluctuation range of the offsets in the radial direction are both larger than the tangential direction. As the load increases, the mean value of the radial offset increases and the magnitude decreases significantly. The mean value of the tangential offset decreases significantly, but the magnitude increases first and then decreases. The load sharing characteristics of the low-speed stage of the NW planetary gear is better than the first stage. With the increase of the load, the load sharing performance of a two-stage planetary transmission gets better and the difference in load sharing between the high-speed and low-speed stages also decreases.

Posterior circulation aneurysms have been regarded as the most challenging for endovascular coiling and microsurgical occlusion. The role of microsurgical treatment is gradually being overlooked and diminishing in the trend of endovascular treatment. As microsurgical occlusion of posterior circulation aneurysms is decreasing, we present our relevant experience to evaluate treatment options and surgical approaches. A retrospective study was conducted in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University between 2016 and 2021. Patients with posterior circulation aneurysms treated by clipping, bypass, and trapping were enrolled and followed up for at least six months. We included 50 patients carrying 53 posterior circulation aneurysms, 43 of whom had aneurysm ruptures. The posterior cerebral artery and posterior inferior cerebellar artery were the most common aneurysm locations. Direct clipping was performed in 43 patients, while bypass and trapping was performed in six patients. The retrosigmoid, far-lateral, and midline or paramedian suboccipital approaches were performed for those aneurysms in the middle and lower thirds. Aneurysms in the upper third required the lateral supraorbital approach, pterional approach, subtemporal approach, and occipital craniotomy. The lateral supraorbital approach was utilized in seven patients for aneurysms above the posterior clinoid process. Thirty-four patients recovered well with modified Rankin score 0–3 at discharge. No patient experienced aneurysm recurrence during the mean follow-up period of 3.57 years. Microsurgery clipping and bypass should be considered in conjunction with endovascular treatment as a treatment option in posterior circulation aneurysms. The lateral supraorbital approach is a feasible, safe, and simple surgical approach for aneurysms above the posterior clinoid process.

In this study, a deep learning model is proposed to predict groundwater levels. The model is able to accurately complete the prediction task even when the data utilized are insufficient. The hybrid model that we have developed, CNN-LSTM-ML, uses a combined network structure of convolutional neural networks (CNN) and long short-term memory (LSTM) network to extract the time dependence of groundwater level on meteorological factors, and uses a meta-learning algorithm framework to ensure the network’s performance under sample conditions. The study predicts groundwater levels from 66 observation wells in the middle and lower reaches of the Heihe River in arid regions and compares them with other data-driven models. Experiments show that the CNN-LSTM-ML model outperforms other models in terms of prediction accuracy in both the short term (1 month) and long term (12 months). Under the condition that the training data are reduced by 50%, the MAE of the proposed model is 33.6% lower than that of LSTM. The results of ablation experiments show that CNN-LSTM-ML is 26.5% better than the RMSE of the original CNN-LSTM structure. The model provides an effective method for groundwater level prediction and contributes to the sustainable management of water resources in arid regions.

ObjectiveThe etiology and pathogenesis of preeclampsia (PE) remain unclear, and ideal biomarkers for the early detection of PE are scarce. The involvement of the competing endogenous RNA (ceRNA) hypothesis in PE is only partially understood. The present study aimed to delineate a regulatory network in PE comprised of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) via ceRNA profiles from human umbilical vein endothelial cells (HUVECs) to further reveal the pathogenesis of PE and potential biomarkers.MethodsDifferentially expressed mRNAs, circRNAs, and lncRNAs were detected in HUVECs from early onset preeclampsia (EOPE) cases (n = 4) and normal pregnancies (n = 4) by microarray analysis. Bioinformatics analysis was performed to systematically analyze the data, and a relevant ceRNA network was constructed. RNAs (ANGPT2, LIPG, hsa_circ_0025992, hsa_circ_0090396, hsa_circ_0066955, hsa_circ_0041203, hsa_circ_0018116, lnc-C17orf64-1:1, lnc-SLC27A2-2:1, and lnc-UEVLD-5:1) were validated by quantitative real-time PCR (qRT-PCR) in 10 pairs of HUVECs and placental tissues from PE patients and normal pregnancies. Furthermore, expression of hsa_circ_0025992 was detected in maternal peripheral blood samples from PE patients (n = 24) and normal pregnancies (n = 30) to confirm its potential as a novel biomarker. The receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value.ResultsCompared with HUVECs from normal pregnancies, HUVECs from EOPE cases had 33 differentially expressed mRNAs (DEmRNAs), 272 DEcircRNAs, and 207 DElncRNAs. GO and KEGG analyses of the DERNAs revealed the biological processes and pathways involved in PE. Based on the microarray data and the predicted miRNAs, a ceRNA network was constructed with four mRNAs, 34 circRNAs, nine lncRNAs, and 99 miRNAs. GO and KEGG analyses of the network reinforced the crucial roles of metabolic disorders, the p53 and JAK/STAT signaling pathways in PE. In addition, ROC analysis indicated that hsa_circ_0025992 could be used as a novel biomarker for PE.ConclusionA novel ceRNA network was revealed in PE, and the potential of hsa_circ_0025992 to serve as a new biomarker was confirmed.

Background and Purpose: Fluoxetine is a drug commonly used to treat mental disorders, such as depression and obsessive–compulsive disorder, and some studies have shown that fluoxetine can improve motor and function recovery after stroke. Therefore, we performed a meta-analysis to investigate the efficacy and safety of fluoxetine in the treatment of post-stroke neurological recovery.Methods: PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) that were performed to assess the efficacy and safety of fluoxetine for functional and motor recovery in subacute stroke patients up to October 2020. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and standardized mean difference (SMD) were analyzed and calculated with a fixed effects model.Results: We pooled 6,788 patients from nine RCTs. The primary endpoint was modified Rankin Scale (mRS). Fluoxetine did not change the proportion of mRS ≤ 2 (P = 0.47). The secondary endpoints were Fugl-Meyer Motor Scale (FMMS), Barthel Index (BI), and National Institutes of Health Stroke Scale (NIHSS). Fluoxetine improved the FMMS (P < 0.00001) and BI(P < 0.0001) and showed a tendency of improving NIHSS (P = 0.08). In addition, we found that fluoxetine reduced the rate of new-onset depression (P < 0.0001) and new antidepressants (P < 0.0001).Conclusion: In post-stroke treatment, fluoxetine did not improve participants' mRS and NIHSS but improved FMMS and BI. This difference could result from heterogeneities between the trials: different treatment duration, clinical scales sensitivity, patient age, delay of inclusion, and severity of the deficit.

With the ever-increasing quality and quantity of imaging data in biomedical research comes the demand for computational methodologies that enable efficient and reliable automated extraction of the quantitative information contained within these images. One of the challenges in providing such methodology is the need for tailoring algorithms to the specifics of the data, limiting their areas of application. Here we present a broadly applicable approach to quantification and classification of complex shapes and patterns in biological or other multi-component formations. This approach integrates the mapping of all shape boundaries within an image onto a global information-rich graph and machine learning on the multidimensional measures of the graph. We demonstrated the power of this method by (1) extracting subtle structural differences from visually indistinguishable images in our phenotype rescue experiments using the endothelial tube formations assay, (2) training the algorithm to identify biophysical parameters underlying the formation of different multicellular networks in our simulation model of collective cell behavior, and (3) analyzing the response of U2OS cell cultures to a broad array of small molecule perturbations.

Calcium-dependent protein kinases (CDPKs) are crucial calcium ions (Ca2+) sensors in plants with important roles in signal transduction, plant growth, development, and stress responses. Here, we identified 24 genes encoding CDPKs in Dendrobium officinale using genome-wide analysis. The phylogenetic analysis revealed that these genes formed four groups, with similar structures in the same group. The gene expression patterns following hormone treatments and yeast two-hybrid of homologous CDPK gene pairs with Rbohs showed differences, indicating functional divergence between homologous genes. In addition, the rapid accumulation of hydrogen peroxide (H2O2) and stomatal closure was observed in response to salicylic acid (SA)/jasmonic acid (JA) stress. Our data showed that CDPK9-2 and CDPK20-4 interacted with Rboh D and Rboh H, respectively, and were implicated in the generation of H2O2 and regulation of the stomatal aperture in response to salicylic acid/jasmonic acid treatment. We believe these results can provide a foundation for the functional divergence of homologous genes in D. officinale.

Abstract Background Recombinant chromosome 4 syndrome (rec 4 syndrome) is a rare genetic disorder, predominately resulting from a parental pericentric inversion of chromosome 4. To date, a total of 18 cases of rec (4) syndrome were published in literature. We report the first kindred of rec (4) syndrome analyzed using copy number variation sequencing (CNV-seq). Results A woman with two adverse fetal outcomes was described in the present study. The first fetus presented with severe intrauterine growth restriction, hyposarca, hydrothorax and ascites. The CNV-seq revealed a dup 4q and del 4p. The second fetus presented with cardiovascular disease of ventricular septal defect, overriding aorta and persistent trunk. The CNV-seq revealed a dup 4p and del 4q. We collected 18 rec (4) cases through literature review. Genotype-phenotype correlation analysis was also performed. Conclusion Recombinant 4 syndrome is a rare genetic disorder. It should be divided into two categories according to the alternative recombinant types. The clinical manifestations of rec (4) cases with dup 4q and del 4p are consistent with the Wolf-Hirschhorn syndrome. For cases harboring dup 4p and del 4q, the high incidence of congenital heart disease is prominent.

Environmental pollution due to uncontrolled e-waste recycling activities has been reported in a number of locations in China. In this study, heavy metal pollution from primitive e-waste processing facilities was investigated. The pollution is due to high concentrations of metals present in the surrounding soils and vegetables. The highest enrichment factor values due to e-waste wastewater and waste discharges were found at Anqiaotou Village and Beian Village. Vegetables from the vicinity of the e-waste processing sites were found to have higher heavy metal pollution index values in comparison with those from the background site. The bioaccessibilities of heavy metals were decreased in the order of Cd > Pb > Sn > Zn > Ni > Cr. The e-waste processing site was badly polluted by Cd, Pb, Zn, Ni and Cr, with its pollution level decreased in the following order: Cd > Pb > Cr > Ni > Zn > Sn. Additionally, the greatest risk among six metals in the e-waste processing areas is caused by Cd and Pb. The risks associated with the consumption of contaminated vegetables grown in e-waste processing regions may be a potential health concern.

With the rapid increase of power supply demand, a large amount of stockpiles of coal have been formed during the process of coal excavation and transportation between the mines, ports, power plants and etc. Quantitative parameters, especially the volume of stockpile are important for the planning of coal production and consumption. Although laser scanning can collect the dense 3D coordinates of the stockpile surface for its quantification, stockpiles of coal have irregular shape, size, height, and base conditions, and may be overlapped with each other, which makes it hard to measure the different stockpiles automatically and accurately. This paper proposes an algorithm to extract and measure the stockpiles from the 3D point cloud data using the multi-scale directional curvature. Firstly, the second-order directional curvature analysis along multiple directions and at multiple scales is proposed to extract the distinctive ridge of crest in the point cloud of stockpiles. Then, starting with the crest points, a competitive growing strategy is proposed to accurately locate the points of slope in the stockpile. Finally, the stockpile’s volume is calculated by reconstructing the complete points of crest and slope with many meshes and triangular prisms through the subsurface fitting and surface reconstruction. Experiments on both the synthetic and real point cloud of stockpiles demonstrate that the proposed algorithm can extract the stockpiles with the average accuracy over 93.5% and measure the volume of stockpiles with the average precision over 93.7%. It is promising for automatically measuring the stockpiles like sand, soybean, etc., and facilitating the scientific storage and transportation management, as well as the maintenance of safety inventory during operation.

In this paper, a potential energy based slice grouping method was proposed to calculate the mesh stiffness for straight beveloid gears with parallel axes. The mathematical mesh stiffness model was derived. The finite element tooth contact model was developed and the loaded tooth contact analysis was conducted to calculate the mesh stiffness. The verification for the mesh stiffness was conducted with the error 3 %, which proves the feasibility and accuracy. Then, the effects of parameters such as pressure angle, pitch cone angle, and profile shift coefficient on the mesh stiffness were investigated. Results show that the normal pressure angle and the tooth width have obvious effects both on the single tooth and synthesized mesh stiffness. When pressure angle is less than 20°, mesh stiffness will be increased with the increase of pressure angle. However, it decreases rapidly when the pressure angle exceeds 20°. Both the single tooth and synthesized mesh stiffness increase obviously as the tooth width increases. The increase of the cone angle and addendum coefficient have a little effect on the single tooth mesh stiffness, but have the obvious incremental effects on the synthesized mesh stiffness. The contact ratio increases obviously with the increase of the addendum coefficient. The profile shift coefficient and the clearance coefficient have unsubstantial effects both on the single and synthesized mesh stiffness.

The mathematical beveloid gear tooth surface model considering machine tool adjustment errors was derived. The definition and calculation process of tooth surface deviations along the tooth trace and profile directions for beveloid gear were proposed. Also, the solid model and the finite element mesh model of a paralleled beveloid gear pair were developed. Then, the effects of the machine tool adjustment errors including independent helix angle error, independent cone angle error and combined helix and cone angle errors on tooth surface deviation and contact characteristics were investigated. Results show that all the machine tool adjustment errors cause an incremental trend for the tooth profile and tooth trace deviations. And positive errors have the opposite impact on the surface deviation compared with the negative errors. The independent helix angle error has a stronger impact on the tooth surface deviations than the independent cone angle error and combined angle errors. Also, the tooth surface deviations caused by the independent helix angle error, independent cone angle error and combined angle errors have the similar magnitude level as the tooth surface modifications. All the independent helix angle error, independent cone angle error and combined angle errors tend to have deteriorative effects on the mesh characteristics, making edge contact worse, decreasing the contact area, increasing the contact pressure and the transmission error. The independent helix angle error has the strongest impact both on the contact pattern and transmission error, which is similar to the impact on the tooth surface deviations. However, the independent cone angle error shows less effects on the mesh characteristics. Thus the machine tool adjustment errors should be strictly controlled especially for the helix angle error during manufacturing.

Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation) responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV), a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR

c-Rel plays important roles in many inflammatory diseases. Revealing the dynamic expression of c-Rel in disease processes in vivo is critical for understanding c-Rel functions and for developing anti-inflammatory drugs. In this paper, a transgenic mouse line, B6-Tg(c-Rel-luc)(Mlit), which incorporated the transgene firefly luciferase driven by a 14.5-kb fragment containing mouse c-Rel gene Rel promoter, was generated to monitor Rel expression in vivo. Luciferase expression could be tracked in living mice by the method of bioluminescence imaging in a variety of inflammatory processes, including LPS induced sepsis and EAE disease model. The luciferase expression in transgenic mice was comparable to the endogenous Rel expression and could be suppressed by administration of anti-inflammatory drug dexamethasone or aspirin. These results indicate that the B6-Tg(c-Rel-luc)(Mlit) mouse is a valuable animal model to study Rel expression in physiological and pathological processes, and the effects of various drug treatments in vivo.

We introduce the compound interest rate into the continuous version of the online leasing problem and discuss the generalized model by competitive analysis. On the one hand, the optimal deterministic strategy and its competitive ratio are obtained; on the other hand, a nearly optimal randomized strategy is constructed and a lower bound for the randomized competitive ratios is proved by Yao's principle. With the help of numerical examples, the theoretical results show that the interest rate puts off the purchase date and diminishes the uncertainty involved in the decision making.

Background As a new indicator of glycemic management, time in range (TIR) is significantly related to short-term glycemic variability, but whether it is also associated with long-term glycemic variability is still unclear. Objective To investigate the relationship of TIR with coefficient of variability (CV) of HbA1c and HbA1c variability score (HVS) during a long-term follow-up in elderly male patients with type 2 diabetes. Methods Two hundred elderly male type 2 diabetic inpatients from the Second Medical Center of PLA General Hospital were enrolled from January 2007 to January 2011. All of them underwent continuous glucose monitoring (CGM) during hospitalization, and by the baseline TIR derived from CGM, they were divided into TIR≥85% group (n=141) and TIR

The −2/−1 programmed ribosomal frameshifting (−2/−1 PRF) mechanism in porcine reproductive and respiratory syndrome virus (PRRSV) leads to the translation of two additional viral proteins, nonstructural protein 2TF (nsp2TF) and nsp2N. This −2/−1 PRF mechanism is transactivated by a viral protein, nsp1β, and cellular poly(rC) binding proteins (PCBPs). Critical elements for −2/−1 PRF, including a slippery sequence and a downstream C-rich motif, were also identified in 11 simarteriviruses. However, the slippery sequences (XXXUCUCU instead of XXXUUUUU) in seven simarteriviruses can only facilitate −2 PRF to generate nsp2TF. The nsp1β of simian hemorrhagic fever virus (SHFV) was identified as a key factor that transactivates both −2 and −1 PRF, and the universally conserved Tyr111 and Arg114 in nsp1β are essential for this activity. In vitro translation experiments demonstrated the involvement of PCBPs in simarterivirus −2/−1 PRF. Using SHFV reverse genetics, we confirmed critical roles of nsp1β, slippery sequence, and C-rich motif in −2/−1 PRF in SHFV-infected cells. Attenuated virus growth ability was observed in SHFV mutants with impaired expression of nsp2TF and nsp2N. Comparative genomic sequence analysis showed that key elements of −2/−1 PRF are highly conserved in all known arteriviruses except equine arteritis virus (EAV) and wobbly possum disease virus (WPDV). Furthermore, −2/−1 PRF with SHFV PRF signal RNA can be stimulated by heterotypic nsp1βs of all non-EAV arteriviruses tested. Taken together, these data suggest that −2/−1 PRF is an evolutionarily conserved mechanism employed in non-EAV/-WPDV arteriviruses for the expression of additional viral proteins that are important for viral replication. IMPORTANCE Simarteriviruses are a group of arteriviruses infecting nonhuman primates, and a number of new species have been established in recent years. Although these arteriviruses are widely distributed among African nonhuman primates of different species, and some of them cause lethal hemorrhagic fever disease, this group of viruses has been undercharacterized. Since wild nonhuman primates are historically important sources or reservoirs of human pathogens, there is concern that simarteriviruses may be preemergent zoonotic pathogens. Thus, molecular characterization of simarteriviruses is becoming a priority in arterivirology. In this study, we demonstrated that an evolutionarily conserved ribosomal frameshifting mechanism is used by simarteriviruses and other distantly related arteriviruses for the expression of additional viral proteins. This mechanism is unprecedented in eukaryotic systems. Given the crucial role of ribosome function in all living systems, the potential impact of the in-depth characterization of this novel mechanism reaches beyond the field of virology. [ABSTRACT FROM AUTHOR]