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Comparative genomics of closely related bacterial isolates is a powerful method for uncovering virulence and other important genome elements. We determined draft sequences (8-fold coverage) of the genomes of strains JD1 and N40 of Borrelia burgdorferi sensu stricto, the causative agent of Lyme disease, and we compared the predicted genes from the two genomes with those from the previously sequenced B31 genome. The three genomes are closely related and are evolutionarily approximately equidistant ( ≈ 0.5% pairwise nucleotide differences on the main chromosome). We used a Poisson model of nucleotide substitution to screen for genes with elevated levels of nucleotide polymorphisms. The three-way genome comparison allowed distinction between polymorphisms introduced by mutations and those introduced by recombination using the method of phylogenetic partitioning. Tests for recombination suggested that patches of high-density nucleotide polymorphisms on the chromosome and plasmids arise by DNA exchange. The role of recombination as the main mechanism driving B. burgdorferi diversification was confirmed by multilocus sequence typing of 18 clinical isolates at 18 polymorphic loci. A strong linkage between the multilocus sequence genotypes and the major alleles of outer-surface protein C (ospC) suggested that balancing selection at ospC is a dominant force maintaining B. burgdorferi diversity in local populations. We conclude that B. burgdorferi undergoes genome-wide genetic exchange, including plasmid transfers, and previous reports of its clonality are artifacts from the use of geographically and ecological isolated samples. Frequent recombination implies a potential for rapid adaptive evolution and a possible polygenic basis of B. burgdorferi pathogenicity. [ABSTRACT FROM AUTHOR]

Reports on the derivation of a maximum-likelihood estimator (MLE) of bacterial allele frequencies designed for use with presence-absence data. Employment of an explicit stochastic model of the host infection process; Use of the methods to estimate allele frequencies at two outer surface protein loci of the Lyme disease spirochete, Borrelia burgdorferi.

Background: Atherosclerosis (AS) is a chronic progressive inflammatory disease, and plaque stability plays a critical role in preventing acute events. Tanyu Tongzhi formula (TTF), a traditional Chinese medicine, has potential therapeutic effects on AS. Methods: We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40+ monocyte differentiation. AS plaque area, collagen content, and lipid area were assessed using histological staining. AS plaque-related biomarkers (monocyte chemoattractant protein 1 (MCP-1), monocyte plus macrophage (MOMA-2), von Willebrand factor (vWF), CD31, and alpha-smooth muscle actin (a-SMA)) were detected using immunohistochemistry. Inflammatory cytokines were determined using enzyme-linked immunosorbent assay. CD40 mRNA expression was detected by real-time quantitative PCR. CD40+ monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/- mice and peripheral blood mononuclear cells (PBMCs). AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting. Results: TTF treatment reduced AS plaque area, collagen content, and lipid area in AS model mice. Levels of MCP-1, MOMA-2, vWF, and CD31 were decreased, while a-SMA level was increased by TTF in model mice. TTF reduced inflammatory cytokines levels, including tumor necrosis factor receptor-a (TNF-a), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). TTF inhibited CD40+ monocyte differentiation and decreased the number of CD40+/CD40- and Ly6C+/Ly6C- cells and M1/M2 ratio in AS model mice and human PBMCs. Additionally, TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs. Conclusion: TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40+ monocyte differentiation, possibly through the regulation of the AMPK/NF-κB signaling pathway. These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS. [ABSTRACT FROM AUTHOR]

The research is meant to analyze the development of Cheerleading at the new period in our country and to discuss the background. Meanwhile, it is hopeful to layout features and the marketing operation base of" National Cheerleading Compulsory Routine". To render the promotion of "National Cheerleading Compulsory Routine" as the entry point, it is poi nted out such following strategies as to build the extending system, training system, competition system event and culture packaging system. These measures are to provide the reference for marketizational operation of Cheerleading in china and to promote the Cheerleading populruization and development. [ABSTRACT FROM AUTHOR]

Background/aim: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. Materials and methods: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≤ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≥ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). Results: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2DS2-VASc score ≥ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492-3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. Conclusion: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting. [ABSTRACT FROM AUTHOR]

We investigate the temperature-dependent infrared spectroscopy of SrMnSb2, which is a semimetal with multiple Fermi surfaces. A notable blue shift of the plasma minimum in reflectivity upon cooling indicates that the carrier density varies with temperature. In the real part of the optical conductivity , a linearly-increased component which extrapolates to zero conductivity at finite frequency has been identified, which suggests dispersion of gapped Dirac band structures near the Fermi level. A two-Drude model, representing two different types of carriers, is introduced to describe the real part of optical conductivity. We separate the contributions of two-Drude model in dc conductivity, and demonstrate that the transport properties of SrMnSb2 are mainly affected by the narrow-Drude quasiparticles. Compared with the similar phenomena observed in CaMnSb2 and SrMnBi2, we can infer that the two-Drude model is an appropriate approach to investigate the multiband materials in AMnSb2 and AMnBi2 families. [ABSTRACT FROM AUTHOR]

We present an infrared spectroscopy study of charge dynamics in CaCo2As2 single crystal. In this material, the optical conductivity can be described by two Drude components with different scattering rates (1/τ): a broad incoherent background and a narrow Drude component. By monitoring the temperature dependence, we find that only the narrow Drude component is temperature-dependent and determines the transport properties. Especially a Fermi liquid behavior of carriers is revealed by the T2 behavior in the dc resistivity ρn and scattering rate 1/τn, indicating a coherent nature of quasiparticles in the narrow Drude subsystem. [ABSTRACT FROM AUTHOR]

We present magnetotransport studies on a series of BaFe2−xNixAs2 (0.03 ≤ x ≤ 0.10) single crystals. In the underdoped (x = 0.03) non-superconducting sample, the temperature-dependent resistivity exhibits a peak at 22 K, which is associated with the onset of filamentary superconductivity (FLSC). FLSC is suppressed by an external magnetic field in a manner similar to the suppression of bulk superconductivity in an optimally-doped (x = 0.10) compound, suggesting the same possible origin as the bulk superconductivity. Our magnetoresistivity measurements reveal that FLSC persists up to the optimal doping and disappears in the overdoped regime where the long-range antiferromagnetic order is completely suppressed, pointing to a close relation between FLSC and the magnetic order. [ABSTRACT FROM AUTHOR]

Motion recognition provides movement information for people with physical dysfunction, the elderly and motion-sensing games production, and is important for accurate recognition of human motion. We employed three classical machine learning algorithms and three deep learning algorithm models for motion recognition, namely Random Forests (RF), K-Nearest Neighbors (KNN) and Decision Tree (DT) and Dynamic Neural Network (DNN), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). Compared with the Inertial Measurement Unit (IMU) worn on seven parts of body. Overall, the difference in performance among the three classical machine learning algorithms in this study was insignificant. The RF algorithm model performed best, having achieved a recognition rate of 96.67%, followed by the KNN algorithm model with an optimal recognition rate of 95.31% and the DT algorithm with an optimal recognition rate of 94.85%. The performance difference among deep learning algorithm models was significant. The DNN algorithm model performed best, having achieved a recognition rate of 97.71%. Our study validated the feasibility of using multidimensional data for motion recognition and demonstrated that the optimal wearing part for distinguishing daily activities based on multidimensional sensing data was the waist. In terms of algorithms, deep learning algorithms based on multi-dimensional sensors performed better, and tree-structured models still have better performance in traditional machine learning algorithms. The results indicated that IMU combined with deep learning algorithms can effectively recognize actions and provided a promising basis for a wider range of applications in the field of motion recognition.

We performed detailed temperature-dependent optical measurements on optimally doped Ba0.6K0.4Fe2As2 single crystal. We examine the changes of the in-plane optical conductivity spectral weight in the normal state and the evolution of the superconducting condensate in the superconducting state. In the normal state, the low-frequency spectral weight shows a metallic response with an arctan (T) dependence, indicating a T-linear scattering rate behavior for the carriers. A high energy spectral weight transfer associated with the Hund's coupling occurs from the low frequencies below 4000 cm−1 ∼ 5000 cm−1 to higher frequencies up to at least 10 cm−1. Its temperature dependence analysis suggests that the Hund's coupling strength is continuously enhanced as the temperature is reduced. In the superconducting state, the FGT sum rule is conserved according to the spectral weight estimation within the conduction bands, only about 40% of the conduction bands participates in the superconducting condensate indicating that Ba0.6K0.4Fe2As2 is in dirty limit. [ABSTRACT FROM AUTHOR]

Abstract Background De Winter electrocardiograph (ECG) pattern is an atypical presentation of acute myocardial infarction (AMI) due to severe stenosis of the left anterior descending (LAD). Complications of acute aortic dissection (AD) in the setting of acute myocardial infarction (AMI) with de Winter sign are relatively rare and physicians may easily miss the diagnosis of AD. We report a case of patient with acute chest pain and de Winter ECG pattern due to AD involving the left main coronary artery (LM), LAD and left circumflex artery (LCX). Case presentation A 57-year-old male patient was initially diagnosed with AMI and then the diagnosis of acute AD was supported by transthoracic echocardiograph (TTE). After two stents were implanted respectively into the proximal LM-LAD and LM-LCX, he recovered from cardiogenic shock. Two months later, the patient underwent the surgery of ascending aorta replacement. After the surgery, there was no obvious chest discomfort during follow-up. Conclusions When an ECG shows a “de Winter pattern”, we should also consider the possibility of AD which result in LAD occlusion. TTE is a useful tool in screening for AD. Further research is needed to prove that percutaneous coronary intervention (PCI) may be a useful treatment strategy in the case of AD leading to severe LAD occlusion and unstable hemodynamics when there’s no condition to perform aortic replacement surgery immediately.

Abstract The aim of this study was to evaluate the effectiveness and safety of AngioJet rheolytic thrombectomy among patients with high thrombus burden. Routine manual thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) does not improve clinical outcomes and was associated with an increased rate of stroke. However, the safety of mechanical thrombus aspiration is still unknown. This was a retrospective, single-center study involving 621 patients with Thrombolysis In Myocardial Infarction thrombus grade 5. The primary outcome was the composite of major adverse cardiovascular events (MACE) within 12 months. The safety outcome was stroke within 1-year. Propensity matching score was calculated due to the significant baseline differences between the AngioJet rhelytic thrombectomy group and the routine treatment group. AngioJet rheolytic thrombectomy was performed in 117 patients. After propensity-score matching, there was no significant difference both in the incidence of MACE (11.1% vs 17.9%, hazard ratio, 1.641; 95% confidence interval [CI] 0.822 to 3.277, p = 0.161) and the incidences of stroke (1.7% vs 2.6%, hazard ratio 1.522; 95% confidence interval [CI] 0.254 to 9.107, p = 0.646) between two groups at 1-year follow-up. In patients with Thrombolysis In Myocardial Infarction thrombus grade 5, AngioJet rheolytic thrombectomy did not improve clinical outcomes at 1 year. However, AngioJet rheolytic thrombectomy did not increase the risk of stroke in patients with high thrombus burden.

ObjectiveEarly identifying arteriosclerosis in newly diagnosed type 2 diabetes (T2D) patients could contribute to choosing proper subjects for early prevention. Here, we aimed to investigate whether radiomic intermuscular adipose tissue (IMAT) analysis could be used as a novel marker to indicate arteriosclerosis in newly diagnosed T2D patients.MethodsA total of 549 patients with newly diagnosed T2D were included in this study. The clinical information of the patients was recorded and the carotid plaque burden was used to indicate arteriosclerosis. Three models were constructed to evaluate the risk of arteriosclerosis: a clinical model, a radiomics model (a model based on IMAT analysis proceeded on chest CT images), and a clinical-radiomics combined model (a model that integrated clinical-radiological features). The performance of the three models were compared using the area under the curve (AUC) and DeLong test. Nomograms were constructed to indicate arteriosclerosis presence and severity. Calibration curves and decision curves were plotted to evaluate the clinical benefit of using the optimal model.ResultsThe AUC for indicating arteriosclerosis of the clinical-radiomics combined model was higher than that of the clinical model [0.934 (0.909, 0.959) vs. 0.687 (0.634, 0.730), P < 0.001 in the training set, 0.933 (0.898, 0.969) vs. 0.721 (0.642, 0.799), P < 0.001 in the validation set]. Similar indicative efficacies were found between the clinical-radiomics combined model and radiomics model (P = 0.5694). The AUC for indicating the severity of arteriosclerosis of the combined clinical-radiomics model was higher than that of both the clinical model and radiomics model [0.824 (0.765, 0.882) vs. 0.755 (0.683, 0.826) and 0.734 (0.663, 0.805), P < 0.001 in the training set, 0.717 (0.604, 0.830) vs. 0.620 (0.490, 0.750) and 0.698 (0.582, 0.814), P < 0.001 in the validation set, respectively]. The decision curve showed that the clinical-radiomics combined model and radiomics model indicated a better performance than the clinical model in indicating arteriosclerosis. However, in indicating severe arteriosclerosis, the clinical-radiomics combined model had higher efficacy than the other two models.ConclusionRadiomics IMAT analysis could be a novel marker for indicating arteriosclerosis in patients with newly diagnosed T2D. The constructed nomograms provide a quantitative and intuitive way to assess the risk of arteriosclerosis, which may help clinicians comprehensively analyse radiomics characteristics and clinical risk factors more confidently.

BackgroundCerebral microbleeds (CMBs) are common in the hypertensive population and can only be detected with magnetic resonance imaging (MRI). The anticoagulation and thrombolytic regimens for patients with >5 CMBs are different from those for patients with ≤ 5 CMBs. However, MRI is not suitable for evaluating CMBs in patients with MRI contraindications or acute ischemic stroke urgently requiring thrombolysis. We aimed to develop and validate a nomogram combining clinical and brain computed tomography (CT) characteristics for predicting >5 CMBs in a hypertensive population.Materials and methodsIn total, 160 hypertensive patients from 2016 to 2020 who were confirmed by MRI to have >5 (77 patients) and ≤ 5 CMBs (83) were retrospectively analyzed as the training cohort. Sixty-four hypertensive patients from January 2021 to February 2022 were included in the validation cohort. Multivariate logistic regression was used to evaluate >5 CMBs. A combined nomogram was constructed based on the results, while clinical and CT models were established according to the corresponding characteristics. Receiver operating characteristic (ROC) and calibration curves and decision curve analysis (DCA) were used to verify the models.ResultsIn the multivariable analysis, the duration of hypertension, level of homocysteine, the number of lacunar infarcts (LIs), and leukoaraiosis (LA) score were included as factors associated with >5 CMBs. The clinical model consisted of the duration of hypertension and level of homocysteine, while the CT model consisted of the number of LIs and LA. The combined model consisted of the duration of hypertension, level of homocysteine, LI, and LA. The combined model achieved an area under the curve (AUC) of 0.915 (95% confidence interval [CI]: 0.860–0.953) with the training cohort and 0.887 (95% CI: 0.783–0.953) with the validation cohort, which were higher than those of the clinical model [training cohort: AUC, 0.797 (95% CI: 0.726, 0.857); validation cohort: AUC, 0.812 (95% CI: 0.695, 0.899)] and CT model [training cohort: AUC, 0.884 (95% CI: 0.824, 0.929); validation cohort: AUC, 0.868 (95% CI: 0.760, 0.940)]. DCA showed that the clinical value of the combined model was superior to that of the clinical model and CT model.ConclusionA combined model based on clinical and CT characteristics showed good diagnostic performance for predicting >5 CMBs in hypertensive patients.

The incidence of esophageal cancer has obvious genetic susceptibility. Identifying esophageal cancer-related genes plays a huge role in the prevention and treatment of esophageal cancer. Through various sequencing methods, researchers have found only a small number of genes associated with esophageal cancer. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. This method fuses graph convolutional network and logical matrix factorization to effectively identify esophageal cancer-related genes through the association between genes. We call this method GCNLMF which achieved AUC as 0.927 and AUPR as 0.86. Compared with other five methods, GCNLMF performed best. We conducted a case study of the top three predicted genes. Although the association of these three genes with esophageal cancer has not been reported in the database, studies by other reseachers have shown that these three genes are significantly associated with esophageal cancer, which illustrates the accuracy of the prediction results of GCNLMF.

Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad(-/-)) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad(-/-) mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens-1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad(-/-) mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants.Design: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019.Setting: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved.Participants: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations).Interventions: None.Measurements and Main Results: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist.Conclusions: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes. [ABSTRACT FROM AUTHOR]

Given its excellent performance against the pathogens, UV disinfection has been applied broadly in different fields. However, only limited studies have comprehensively investigated the response of bacteria surviving UV irradiation to the environmental antibiotic stress. Here, we investigated the antibiotic susceptibility of Pseudomonas aeruginosa suffering from the UV irradiation. Our results revealed that UV exposure may decrease the susceptibility to tetracycline, ciprofloxacin, and polymyxin B in the survival P. aeruginosa. Mechanistically, UV exposure causes oxidative stress in P. aeruginosa and consequently induces dysregulation of genes contributed to the related antibiotic resistance genes. These results revealed that the insufficient ultraviolet radiation dose may result in the decreased antibiotic susceptibility in the pathogens, thus posing potential threats to the environment and human health.

Background/Aims: Interference with endothelial progenitor cell (EPC) neovascularization is a novel therapeutic target for neovascular-related diseases. Angiotensin Ⅱ (Ang Ⅱ) was found to enhance new vessel formation and aggravated neovascular-related diseases. In this study, we investigated the effects of Ang Ⅱ on EPC neovascular-related functions and explored the underlying mechanisms. Methods: EPCs were cultured from bone marrow derived mononuclear cells. The effects of Ang Ⅱ on EPC proliferation, adhesion, migration, and in vitro tube formation were investigated using the MTT assay, adhesion assay, transwell chamber assay, and in vitro tube formation assay respectively. The underlying mechanisms were explored using Western blotting assay. Results: EPC adhesion, migration and in vitro tube formation were promoted by Ang Ⅱ, and the effects were reversed by RhoA/Rho-associated kinases (ROCK) signaling pathway inhibitors including C3 exoenzyme, GGTI-286 and Y-27632. The active form of RhoA was up-regulated by Ang Ⅱ and this effect was abolished by C3 exoenzyme. Moreover, RhoA silencing resulted in a notable inhibition of EPC adhesion, migration and in vitro tube formation, suggesting that RhoA activation played a pivotal role in Ang Ⅱ angiogenic effect. The results also demonstrated that phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun-NH2 kinase was elevated by Ang Ⅱ and attenuated by C3 exoenzyme, GGTI-286 and Y-27632. The enhancing effects of Ang Ⅱ on EPC adhesion, migration and in vitro vasculogenesis were reversed by p38 inhibitor SB202190 and JNK inhibitor SP600125. Conclusion: Ang Ⅱ may enhance EPC neovascular-related functions through activating RhoA/ ROCK and MAPK signaling pathway.

Abstract Background With approximately one-third of their genomes consisting of linear and circular plasmids, the Lyme disease agent cluster of species has the most complex genomes among known bacteria. We report here a comparative analysis of plasmids in eleven Borreliella (also known as Borrelia burgdorferi sensu lato) species. Results We sequenced the complete genomes of two B. afzelii, two B. garinii, and individual B. spielmanii, B. bissettiae, B. valaisiana and B. finlandensis isolates. These individual isolates carry between seven and sixteen plasmids, and together harbor 99 plasmids. We report here a comparative analysis of these plasmids, along with 70 additional Borreliella plasmids available in the public sequence databases. We identify only one new putative plasmid compatibility type (the 30th) among these 169 plasmid sequences, suggesting that all or nearly all such types have now been discovered. We find that the linear plasmids in the non-B. burgdorferi species have undergone the same kinds of apparently random, chaotic rearrangements mediated by non-homologous recombination that we previously discovered in B. burgdorferi. These rearrangements occurred independently in the different species lineages, and they, along with an expanded chromosomal phylogeny reported here, allow the identification of several whole plasmid transfer events among these species. Phylogenetic analyses of the plasmid partition genes show that a majority of the plasmid compatibility types arose early, most likely before separation of the Lyme agent Borreliella and relapsing fever Borrelia clades, and this, with occasional cross species plasmid transfers, has resulted in few if any species-specific or geographic region-specific Borreliella plasmid types. Conclusions The primordial origin and persistent maintenance of the Borreliella plasmid types support their functional indispensability as well as evolutionary roles in facilitating genome diversity. The improved resolution of Borreliella plasmid phylogeny based on conserved partition-gene clusters will lead to better determination of gene orthology which is essential for prediction of biological function, and it will provide a basis for inferring detailed evolutionary mechanisms of Borreliella genomic variability including homologous gene and plasmid exchanges as well as non-homologous rearrangements.

Abstract Background Automated bioinformatics workflows are more robust, easier to maintain, and results more reproducible when built with command-line utilities than with custom-coded scripts. Command-line utilities further benefit by relieving bioinformatics developers to learn the use of, or to interact directly with, biological software libraries. There is however a lack of command-line utilities that leverage popular Open Source biological software toolkits such as BioPerl (http://bioperl.org) to make many of the well-designed, robust, and routinely used biological classes available for a wider base of end users. Results Designed as standard utilities for UNIX-family operating systems, BpWrapper makes functionality of some of the most popular BioPerl modules readily accessible on the command line to novice as well as to experienced bioinformatics practitioners. The initial release of BpWrapper includes four utilities with concise command-line user interfaces, bioseq, bioaln, biotree, and biopop, specialized for manipulation of molecular sequences, sequence alignments, phylogenetic trees, and DNA polymorphisms, respectively. Over a hundred methods are currently available as command-line options and new methods are easily incorporated. Performance of BpWrapper utilities lags that of precompiled utilities while equivalent to that of other utilities based on BioPerl. BpWrapper has been tested on BioPerl Release 1.6, Perl versions 5.10.1 to 5.25.10, and operating systems including Apple macOS, Microsoft Windows, and GNU/Linux. Release code is available from the Comprehensive Perl Archive Network (CPAN) at https://metacpan.org/pod/Bio::BPWrapper. Source code is available on GitHub at https://github.com/bioperl/p5-bpwrapper. Conclusions BpWrapper improves on existing sequence utilities by following the design principles of Unix text utilities such including a concise user interface, extensive command-line options, and standard input/output for serialized operations. Further, dozens of novel methods for manipulation of sequences, alignments, and phylogenetic trees, unavailable in existing utilities (e.g., EMBOSS, Newick Utilities, and FAST), are provided. Bioinformaticians should find BpWrapper useful for rapid prototyping of workflows on the command-line without creating custom scripts for comparative genomics and other bioinformatics applications.

Accumulating evidence has demonstrated that endothelial progenitor cells (EPCs) could facilitate the reendothelialization of injured arteries by replacing the dysfunctional endothelial cells, thereby suppressing the formation of neointima. Meanwhile, other findings suggest that EPCs may be involved in the pathogenesis of age-related vascular remodeling. This review is presented to summarize the characteristics of EPCs and age-related vascular remodeling. In addition, the role of EPCs in age-related vascular remodeling and possible solutions for improving the therapeutic effects of EPCs in the treatment of age-related diseases are discussed.

In December, 2006, a group of 26 software developers from some of the most widely used life science programming toolkits and phylogenetic software projects converged on Durham, North Carolina, for a Phyloinformatics Hackathon, an intense five-day collaborative software coding event sponsored by the National Evolutionary Synthesis Center (NESCent). The goal was to help researchers to integrate multiple phylogenetic software tools into automated workflows. Participants addressed deficiencies in interoperability between programs by implementing “glue code” and improving support for phylogenetic data exchange standards (particularly NEXUS) across the toolkits. The work was guided by use-cases compiled in advance by both developers and users, and the code was documented as it was developed. The resulting software is freely available for both users and developers through incorporation into the distributions of several widely-used open-source toolkits. We explain the motivation for the hackathon, how it was organized, and discuss some of the outcomes and lessons learned. We conclude that hackathons are an effective mode of solving problems in software interoperability and usability, and are underutilized in scientific software development.

The mycobactin siderophore system is present in many Mycobacterium species, including M. tuberculosis and other clinically relevant mycobacteria. This siderophore system is believed to be utilized by both pathogenic and nonpathogenic mycobacteria for iron acquisition in both in vivo and ex vivo iron-limiting environments, respectively. Several M. tuberculosis genes located in a so-called mbt gene cluster have been predicted to be required for the biosynthesis of the core scaffold of mycobactin based on sequence analysis. A systematic and controlled mutational analysis probing the hypothesized essential nature of each of these genes for mycobactin production has been lacking. The degree of conservation of mbt gene cluster orthologs remains to be investigated as well. In this study, we sought to conclusively establish whether each of nine mbt genes was required for mycobactin production and to examine the conservation of gene clusters orthologous to the M. tuberculosis mbt gene cluster in other bacteria. We report a systematic mutational analysis of the mbt gene cluster ortholog found in Mycobacterium smegmatis. This mutational analysis demonstrates that eight of the nine mbt genes investigated are essential for mycobactin production. Our genome mining and phylogenetic analyses reveal the presence of orthologous mbt gene clusters in several bacterial species. These gene clusters display significant organizational differences originating from an intricate evolutionary path that might have included horizontal gene transfers. Altogether, the findings reported herein advance our understanding of the genetic requirements for the biosynthesis of an important mycobacterial secondary metabolite with relevance to virulence. [ABSTRACT FROM AUTHOR]

Trophoblast fusion in placenta is an important event for preservation of a healthy pregnancy. This process takes place throughout the pregnancy and is crucial for the formation of syncytiotrophoblast layer. Syncytin-1 and syncytin-2 are strong candidate regulators of fusion from retroviral origin. Syncytin-A and syncytin-B are other candidates from retroviral origin in Muridae. The active role of syncytin in driving fusion of trophoblast has been identified, but its fusion mechanism is still unclear. As an intact retroviral envelope protein, syncytin-A shares similar structure profiling with other viral envelope fusion proteins, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR, respectively). In this paper, we showed that SynA 1 + 2 of syncytin-A (residues 445-536, including predicted NHR, CHR, and a natural linker) could form trimer and exhibited significant α-helix structure and high thermo-stability. Limited proteolysis result identified a stable protease-resistant core of SynA 1 + 2, which was in good agreement with computational modeling data. NHR and CHR could interact with each other in vitro, too. Different from the previous studies, the disulfide-bonded linker was apparently vital to the stability of fusion core structure. By biological assays, NHR was shown to be inhibitive to cell-cell fusion, with IC50 value about 5.4 µM, but CHR seemed to have no inhibitory activity even at 50 µM. From both biochemical and functional data, we first gave an explanation how syncytin-A mediated cell fusion. The insight into the mechanism of syncytin-A-mediated cell-cell fusion may provide a crucial clue to placental cytotrophoblast morphogenesis. [ABSTRACT FROM AUTHOR]

The prevalence of congenital heart disease (CHD) in Tibet has not been fully investigated. The aim of this study was to illustrate and compare the prevalence of symptomatic CHD and its major subtypes in Tibetan children at different altitudes. A total of 5,790 children from regions at altitudes of 3,500 to 4,100 m (group L) and 4,548 children from 4,200 to 4,900 m (group H) were compared for CHD prevalence. Group H had greater prevalence of total CHD (12.09 vs 4.32 per 1,000, p <0.001), patent ductus arteriosus (PDA, 7.70 vs 1.38 per 1,000, p <0.001), and atrial septal defect (ASD, 3.52 vs 2.25 per 1,000, p = 0.23) than group L. The differences were more remarkable in women (CHD, 18.63 vs 4.88 per 1,000, p <0.001; PDA, 11.53 vs 1.74 per 1,000, p <0.001; ASD, 5.32 vs 2.79 per 1,000, p = 0.15). No significant difference was observed in the prevalence of ventricular septal defect between the 2 groups (0.44 vs 0.35 per 1,000, p >0.05). The most common cardiac defect was ASD (52.0%) in group L compared with PDA (63.6%) in group H. In group L, women had slightly and insignificantly greater prevalence of total CHD, PDA, and ASD than men. In contrast, the prevalence was almost threefold greater in women than men in group H. In conclusion, the CHD prevalence and composition differed significantly between populations of school children living above and below 4,200 m. [ABSTRACT FROM AUTHOR]

Human Lyme disease is caused by a number of related Borrelia burgdorferi sensu lato species. We report here the complete genome sequence of Borrelia sp. isolate SV1 from Finland. This isolate is to date the closest known relative of B. burgdorferi sensu stricto, but it is sufficiently genetically distinct from that species that it and its close relatives warrant its candidacy for new-species status. We suggest that this isolate should be named "Borrelia finlandensis." [ABSTRACT FROM AUTHOR]

This study aimed to develop an anthelmintic that leaves no residues and is safe and efficient for use in cows. We constructed classical pseudoternary phase diagrams using experimental animal data to optimize and characterize the eprinomectin nanoemulsion formulas. The emulsion samples prepared with ethyl acetate, polysorbate 80, and 1-propanediol as the main components were transparent and uniform when observed under a Hitachi transmission electron microscope (TEM) system. A Mastersizer 3000 laser particle size analyzer was used to determine the particle sizes of the prepared nanoemulsions. The nanoemulsions were homogeneously dispersed, with an average particle size of 12.61 nm and a polydispersity index of (PDI) 0.297. High-performance liquid chromatography confirmed no statistically significant changes in the samples after 24 months at 4 °C, 25 °C, and 37 °C; the samples exhibited long-term stability. The PK/PD studies confirmed that the injection of eprinomectin nanoemulsions at a dose of 0.2 mg/kg body weight was effective, with a withdrawal period of 0 days for dairy cows. The total extermination rate of the nanoemulsions against adult nematodes was 98.40±1.52%. The AUC milk/plasma ratio was 0.67±0.03. The optimal dose was found to be 0.2 mg/kg body weight.

Aim: To investigate the seroprevalence and evolutionary dynamics of hepatitis E virus (HEV) and assess the ancestor of HEVs in China's Shandong Province., Methods: A total of 2028 serum, 60 fecal and 82 bile samples were collected from the general human population, patients and swine, respectively. This seroepidemiological study was conducted using an immunnosorbent assay and HEV RNA was detected by the reverse transcription-nested polymerase chain reaction (RT-nPCR) method. Complete genome sequences of the prevalent strains (CH-YT-HEV01, CH-YT-HEV02 and CH-YT-sHEV01) were determined, and the sequences were analyzed phylogenetically. In addition, the evolutionary dynamics of three HEV isolates were determined using the framework of coalescent analysis in the program package BEAST, and the time of the most recent common ancestors (TMRCAs) of China-indigenous genotype 4 HEV isolates was calculated., Results: The overall viral burden in the general human population was 0.1%, and the positive rates of anti-HEV IgG and IgM in the serum specimens were 25.1% (509/2028) and 2.3% (51/2028), respectively. In addition, IgG positivity increased with age. The phylogenetic analysis based on the full-length nucleotide sequences showed that the strain CH-YT-HEV02 was directly related to CH-YT-sHEV01 with a 94% identity, suggesting that they were involved in cross-species transmission. The isolate CH-YT-HEV01 was close to HB-3 and CHN-SD-sHEV with a bootstrap value of 100%, sharing a 96.1%-96.4% identity with each other. Surprisingly, the HB-3 strain was a representative strain prevalent in swine in Hubei, and the isolate CHN-SD-sHEV was obtained from swine in Shandong in a previous report. TMRCA for the clade of CH-YT-HEV01 and HB-3 was 2003, which was consistent with the TMRCA for the clade of CHN-SD-sHEV and HB-3, and they were both earlier than the TMRCA for the clade of CH-YT-HEV01 and CHN-SD-sHEV (2004)., Conclusion: The strains CH-YT-HEV01, CHN-SD-sHEV and HB-3 are involved in trans-regional transmission, and the ancestors of HEVs in Shandong come from Hubei Province.