The transmission networks of Plasmodium vivax characterize how the parasite transmits from one location to another, which are informative and insightful for public health policy makers to accurately predict the patterns of its geographical spread. However, such networks are not apparent from surveillance data because P. vivax transmission can be affected by many factors, such as the biological characteristics of mosquitoes and the mobility of human beings. Here, we pay special attention to the problem of how to infer the underlying transmission networks of P. vivax based on available tempo-spatial patterns of reported cases.
We first define a spatial transmission model, which involves representing both the heterogeneous transmission potential of P. vivax at individual locations and the mobility of infected populations among different locations. Based on the proposed transmission model, we further introduce a recurrent neural network model to infer the transmission networks from surveillance data. Specifically, in this model, we take into account multiple real-world factors, including the length of P. vivax incubation period, the impact of malaria control at different locations, and the total number of imported cases.
We implement our proposed models by focusing on the P. vivax transmission among 62 towns in Yunnan province, People's Republic China, which have been experiencing high malaria transmission in the past years. By conducting scenario analysis with respect to different numbers of imported cases, we can (i) infer the underlying P. vivax transmission networks, (ii) estimate the number of imported cases for each individual town, and (iii) quantify the roles of individual towns in the geographical spread of P. vivax.
The demonstrated models have presented a general means for inferring the underlying transmission networks from surveillance data. The inferred networks will offer new insights into how to improve the predictability of P. vivax transmission.
The transmission of Plasmodium vivax has induced enormous public health problems at the global level. Natural transmission of P. vivax depends on interactions between anopheles mosquitoes and human beings. There are two important factors that influence its geographical spread. First, different locations may have different risks of infection due to their heterogeneous environmental and demographical profiles. Second, human mobility may bring pathogens from high-transmission locations to low-transmission locations. In view of this, to effectively and efficiently control the geographical spread of P. vivax, it would be desirable for us to characterize how it transmits from one location to another. To achieve this, we first build a spatial transmission model to characterize both the heterogeneous infection risks at individual locations and the underlying mobility of infected populations. By doing so, we can further infer the underlying P. vivax transmission networks from tempo-spatial surveillance data by using a machine learning method (i.e., based on a recurrent neural network model). Our study offers new insights into malaria surveillance and control from the viewpoint of both system modeling and machine learning.
The objective of this study was to investigate the association between chronic back pain and urinary incontinence in women.
This study was a cross-sectional, observational study.
There are numerous factors associated with the development of back pain, yet little consideration has been given to the pelvic floor musculature and dysfunction of this musculature which may also cause urinary incontinence. Currently, limited research exists evaluating the relationship between back pain and urinary incontinence.
Methods and Measures
Data from a sample of 2,341 women from the Kentucky Women’s Health Registry were used for analysis. The primary variables of interest were self-reported chronic back pain (CBP) and stress urinary incontinence (SUI), with stress urinary incontinence serving as the primary dependent variable. Simple comparisons were performed using chi-square tests and two-sample t-tests, and multivariable associations were assessed using binary logistic regression.
Reports of stress urinary incontinence were higher in women reporting CBP than those not reporting CBP (49.0% vs. 35.2%, p<0.01). After controlling for potential confounders, the adjusted SUI odds ratio for CBP versus not was 1.44 (95% CI 1.11, 1.86).
Women who report CBP have an increased odds of having SUI. Therefore, clinicians must consider this association and the relationship of relevant trunk muscles, including pelvic floor musculature, in patients presenting with CBP and/or UI.
Objective: To clarify the precise characteristics of human hepatic progenitor cells (HPCs) for future cytotherapy in liver diseases.
Methods: Hepatic progenitor-like cells were isolated and cultured from the livers of patients who had undergone partial hepatectomy for various pathologies but displayed no sign of hepatic dysfunction. These cells were characterized by transcriptomic profiling, quantitative real-time PCR and immunocyto/histochemistry.
Results:Cultured HPCs contained polygonal, high nucleus/cytoplasm ratio and exhibited a global gene expression profile similar (67.8%) to that of primary hepatocytes. Among the genes with more than 20-fold higher expression in HPCs were a progenitor marker (CD90), a pentraxin-related gene (PTX3), collagen proteins (COL5A2, COL1A1 and COL4A2), cytokines (EGF and PDGFD), metabolic enzymes (CYBRD1, BCAT1, TIMP2 and PAM), a secreted protein (SPARC) and an endothelial protein C receptor (PROCR). Moreover, eight markers (ALB, AFP, CK8, CK18, CK19, CD90, CD117 and Oval-6) previously described as HPC markers were validated by qRT-PCR and/or immunocyto/histochemistry. Interestingly, human HPCs were also positive for the hematopoietic cell markers CD45 and CD109. Finally, we characterized the localization of HPCs in the canals of Hering and periportal areas with six previously described markers (Oval-6, CK8, CK18, CK19, CD90 and CD117) and two potential markers (CD45 and CD109).
Conclusion: The human HPCs are highly similar to primary hepatocytes in their transcriptional profiles. The CD45 and CD109 markers could potentially be utilized to identify and isolate HPCs for further cytotherapy of liver diseases.
Human hepatic progenitor cell; Immunocytochemistry; Transcriptional profile
By the end of 2012, China had launched 16 BeiDou-2 navigation satellites that include six GEOs, five IGSOs and five MEOs. This has provided initial navigation and precise pointing services ability in the Asia-Pacific regions. In order to assess the navigation and positioning performance of the BeiDou-2 system, Wuhan University has built up a network of BeiDou Experimental Tracking Stations (BETS) around the World. The Position and Navigation Data Analyst (PANDA) software was modified to determine the orbits of BeiDou satellites and provide precise orbit and satellite clock bias products from the BeiDou satellite system for user applications. This article uses the BeiDou/GPS observations of the BeiDou Experimental Tracking Stations to realize the BeiDou and BeiDou/GPS static and kinematic precise point positioning (PPP). The result indicates that the precision of BeiDou static and kinematic PPP reaches centimeter level. The precision of BeiDou/GPS kinematic PPP solutions is improved significantly compared to that of BeiDou-only or GPS-only kinematic PPP solutions. The PPP convergence time also decreases with the use of combined BeiDou/GPS systems.
BeiDou navigation satellite system; Position and Navigation Data Analyst (PANDA); BeiDou Experimental Tracking Stations (BETS); Precise Point Positioning (PPP)
Human facial morphology is a combination of many complex traits. Little is known about the genetic basis of common facial morphological variation. Existing association studies have largely used simple landmark-distances as surrogates for the complex morphological phenotypes of the face. However, this can result in decreased statistical power and unclear inference of shape changes. In this study, we applied a new image registration approach that automatically identified the salient landmarks and aligned the sample faces using high density pixel points. Based on this high density registration, three different phenotype data schemes were used to test the association between the common facial morphological variation and 10 candidate SNPs, and their performances were compared. The first scheme used traditional landmark-distances; the second relied on the geometric analysis of 15 landmarks and the third used geometric analysis of a dense registration of ∼30,000 3D points. We found that the two geometric approaches were highly consistent in their detection of morphological changes. The geometric method using dense registration further demonstrated superiority in the fine inference of shape changes and 3D face modeling. Several candidate SNPs showed potential associations with different facial features. In particular, one SNP, a known risk factor of non-syndromic cleft lips/palates, rs642961 in the IRF6 gene, was validated to strongly predict normal lip shape variation in female Han Chinese. This study further demonstrated that dense face registration may substantially improve the detection and characterization of genetic association in common facial variation.
Heritability of human facial appearance is an intriguing question to the general public and researchers. Although it is known that some facial features are highly heritable, the exact genetic basis is unknown. Previous studies used simple linear measurements such as landmark distances, to evaluate the facial shape variation. Such approaches, although easy to carry out, may lack statistical power and miss complex morphological changes. In this study, we utilized a new 3D face registration method that enables subtle differences to be detected at high resolution 3D images. Based on this, we tried to test and characterize the associations of 10 candidate genetic variants to common facial morphological variations. Different types of phenotype data were extracted and compared in the association tests. Our results show that geometry based data performed better than simple distance based data. Furthermore, high density geometric data outstood the others in capturing small shape changes and modeling the 3D face visualization. Interestingly, a genetic variant from IRF6 gene, which is also a well-known risk factor of non-syndrome cleft lip, was found to strongly predispose the mouth shape in Han Chinese females.
It is very difficult to prevent pulmonary tuberculosis (TB) due to the lack of specific and diagnostic markers, which could lead to a high incidence of pulmonary TB. We screened the differentially expressed serum microRNAs (miRNAs) as potential biomarkers for the diagnosis of pulmonary TB.
In this study, serum miRNAs were screened using the Solexa sequencing method as the potential biomarkers for the diagnosis of pulmonary TB. The stem-loop quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was used to verify differentially expressed serum miRNAs. The receiver operating characteristic (ROC) curve and logistic regression model were used to analyze the sensitivity and specificity of the single miRNA and a combination of miRNAs for diagnosis, respectively. Using the predicted target genes, we constructed the regulatory networks of miRNAs and genes that were related to pulmonary TB.
The Solexa sequencing data showed that 91 serum miRNAs were differentially expressed in pulmonary TB patients, compared to healthy controls. Following qRT-PCR confirmation, six serum miRNAs (hsa-miR-378, hsa-miR-483-5p, hsa-miR-22, hsa-miR-29c, hsa-miR-101 and hsa-miR-320b) showed significant difference among pulmonary TB patients, healthy controls (P<0.001) and differential diagnosis groups (including patients with pneumonia, lung cancer and chronic obstructive pulmonary disease) (P<0.05). The logistic regression analysis of a combination of six serum miRNAs revealed that the sensitivity and the specificity of TB diagnosis were 95.0% and 91.8% respectively. The miRNAs-gene regulatory networks revealed that several miRNAs may regulate some target genes involved in immune pathways and participate in the pathogenesis of pulmonary TB.
Our study suggests that a combination of six serum miRNAs have great potential to serve as non-invasive biomarkers of pulmonary TB.
Bone marrow-derived macrophages (BMMs) treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), differentiate into GM-CSF-induced mouse bone marrow-derived macrophages (GM-BMMs) or M-CSF-induced mouse bone marrow-derived macrophages (M-BMMs), which have an M1 or M2 profile, respectively. GM-BMMs produce large amounts of proinflammatory cytokines and mediate resistance to pathogens, whereas M-BMMs produce anti-inflammatory cytokines that contribute to tissue repair and remodeling. M-BMMs stimulated with lipopolysaccharide (LPS) are in an antiinflammatory state, with an IL-12low IL-10high phenotype. However, the regulation of this process remains unclear. Klf10 belongs to the family of Krüppel-like transcription factors and was initially described as a TGF-β inducible early gene 1. IL-12p40 is upregulated in LPS-stimulated M-BMMs from Klf10-deficient mice, but downregulated during Klf10 overexpression. Klf11, another member of the Krüppel-like factor family, can also repress the production of IL-12p40. Furthermore, Klf10 binds to the CACCC element of the IL-12p40 promoter and inhibits its transcription. We have therefore identified Klf10 as a transcription factor that regulates the expression of IL-12p40 in M-BMMs.
IL-12p40; Inflammatory factor; Klf10; Macrophage; Transcription factor
Many neurodegenerative diseases are characterized by the accumulation of insoluble protein aggregates, including neurofibrillary tangles comprised of tau in Alzheimer’s disease and Lewy bodies composed of α-synuclein in Parkinson’s disease. Moreover, different pathological proteins frequently codeposit in disease brains. To test whether aggregated α-synuclein can directly cross-seed tau fibrillization, we administered preformed α-synuclein fibrils assembled from recombinant protein to primary neurons and transgenic mice. Remarkably, we discovered two distinct strains of synthetic α-synuclein fibrils that demonstrated striking differences in the efficiency of cross-seeding tau aggregation, both in neuron cultures and in vivo. Proteinase K digestion revealed conformational differences between the two synthetic α-synuclein strains and also between sarkosyl-insoluble α-synuclein extracted from two subgroups of Parkinson’s disease brains. We speculate that distinct strains of pathological α-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies.
Objective: To observe the periodontal healing of autogenously transplanted teeth loaded orthodontically after autotransplantation in Beagle dogs. Methods: Forty-eight teeth were autogenously transplanted, 24 of which were loaded postoperatively with orthodontic force at different time points and for different durations. Periodontal healing was evaluated by probing pocket depth (PPD), the expression of relevant proteins, and histomorphometric analyses. Results: The dental pockets of loaded and non-loaded teeth were both much deeper after the first postoperative week than before transplantation (P<0.05). Later, the PPD, which was measured after postoperative weeks 1, 3, 5, 9 and 13, gradually became shallow. The expressions of alkaline phosphatase (ALP) and basic fibroblast growth factor (bFGF) were higher in loaded teeth than in non-loaded teeth (P<0.05), and in groups subjected to two weeks duration of loading than in other groups at the same load time point (P<0.05). For the same load duration, the expressions of ALP and bFGF in teeth loaded after postoperative week 4 were higher than those of other treatments (P<0.05). According to histomorphometric analyses, an orthodontic force on transplanted teeth applied after postoperative weeks 4 or 8 for two weeks duration should be favorable for periodontal healing. Conclusions: It is advisable to apply an appropriate magnitude of force on autotransplanted teeth, such as orthodontic force, at appropriate time points and for a suitable duration, to achieve the optimal clinical prognosis following autogenous tooth transplantation. These results may serve as a basis for subsequent studies in humans so as to make clinical improvements.
Autogenous tooth transplantation; Periodontium healing; Orthodontic load
Hypervitaminosis A and alcoholism can result in a low mineral density and compromised regenerative capacity of bone, thus delaying implant osteointegration. The inhibitory effect of all-trans retinoic acid on osteoblastogenesis is considered to be one of the mechanisms. We hypothesized that heterodimeric bone morphogenetic protein-2/7 could antagonize all-trans retinoic acid and enhance osteoblastogenesis, with an aim to accelerate and enhance bone regeneration and implant osteointegration.
Materials and Methods
We applied 5 ng/ml or 50 ng/ml bone morphogenetic protein-2/7 to restore the osteoblastogenesis of pre-osteoblasts (MC3T3-E1 cell line) that was inhibited by 1 µM all-trans retinoic acid. We evaluated the efficacy by assessing cell numbers (proliferation), alkaline phosphatase activity (a marker for early differentiation), osteocalcin (a marker for late differentiation), calcium deposition (a marker for final mineralization) and the expression of osteoblastogenic genes (such as Runx2, Collagen Ia, alkaline phosphatase and osteocalcin) at different time points.
All-trans retinoic acid significantly inhibited the expression of all the tested osteoblastogenic genes and proteins except alkaline phosphatase activity. In the presence of ATRA, 50 ng/ml bone morphogenetic protein-2/7 not only completely restored but also significantly enhanced all the osteoblastogenic genes and proteins. On the 28th day, mineralization was completely inhibited by all-trans retinoic acid. In contrast, 50 ng/ml BMP-2/7 could antagonize ATRA and significantly enhance the mineralization about 2.5 folds in comparison with the control treatment (no ATRA, no BMP2/7).
Heterodimeric bone morphogenetic protein-2/7 bears a promising application potential to significantly promote bone regeneration and implant osteointegration for the patients with hypervitaminosis A and alcoholism.
Previous studies had shown that sagittal spinal and pelvic morphology may be associated with the development and progression of adolescent idiopathic scoliosis, but the predictive value of initial spinal and pelvic morphology on the curve progression during brace treatment is unknown. The objective of this study was to evaluate the relation between initial spinopelvic morphology and the risk of curve progression of adolescent idiopathic scoliosis with the Milwaukee brace.
Materials and methods
From 2002 to 2007, adolescent idiopathic scoliosis (single thoracic curve with apex at or above T8) was treated with the Milwaukee brace in 60 girls. Initial standing, full-length lateral radiographs were made and seven sagittal radiographic parameters of spinal and pelvic alignment were measured. Patients were followed until skeletal maturity or progression of Cobb angle >45°. The progression of curve was defined as an increase of Cobb angle ≥6° at final follow-up or progression to surgery during brace treatment.
The 45 patients (75.0 %) who had successful control of curve progression were initially significantly more skeletally mature (higher mean Risser sign) than the 15 patients (25.0 %) who had curve progression. The initial mean Cobb angle was similar between the stable and progressed groups. The mean pelvic tilt, T1-spinopelvic inclination and T9-spinopelvic inclination angles were significantly greater in the stable group than in the progressed group and these three angles were independent predictors for curve progression during brace treatment. There were no significant differences between the stable and progressed groups in initial mean pelvic incidence, sacral slope, thoracic kyphosis or lumbar lordosis angles. Pre-bracing pelvic tilt ≤−0.5° was strongly predictive and T1-spinopelvic inclination ≤3.5° was moderately predictive of curve progression during the Milwaukee brace treatment.
Initial pelvic tilt and spinopelvic inclination angles may predict the curve progression and treatment outcome of adolescent idiopathic scoliosis with the Milwaukee brace.
Adolescent idiopathic scoliosis; Spinopelvic morphology; Brace treatment; Curve progression
Objectives. To investigate the six-week influence of acupuncture on sleep quality and daytime functioning in primary insomnia. Methods. The study was a double-dummy, single-blinded, randomized, placebo-controlled clinical trial. A total of 180 patients with primary insomnia were randomly assigned to 3 groups: verum group underwent verum acupuncture plus placebo; estazolam group underwent estazolam plus sham acupuncture; sham group underwent sham acupuncture plus placebo. The outcome was measured by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the 36-item short-form health survey (SF-36). Results. The three groups showed significant improvement compared with the pretreatment baseline. Compared with the other two groups, the verum group reported improved sleep quality (SQ) and vitality (VT), decreased daytime dysfunction (DD) and sleepiness (ESS score). The differences were kept from the treatment period to the end of the trial. Discussion. Verum acupuncture appeared to be more effective in increasing sleep quality and daytime functioning than sham acupuncture and estazolam. Trial Registration. The trial is registeded with ClinicalTrials.gov ISRCTN12585433.
Microbial fuel cells (MFCs) are a class of ideal technologies that function via anaerobic respiration of electricigens, which bring current generation and environmental restoration together. An in-depth understanding of microbial metabolism is of great importance in engineering microbes to further improve their respiration. We employed flux balance analysis and selected Fe(iii) as a substitute for the electrode to simulate current-generating metabolism of Geobacter sulfurreducens PCA with a fixed acetate uptake rate. Simulation results indicated the fluxes of reactions directing acetate towards dissimilation to generate electrons increased under the suboptimal growth condition, resulting in an increase in the respiration rate and a decrease in the growth rate. The results revealed the competitive relationship between oxidative respiration and cell growth during the metabolism of microbe current generation. The results helped us quantitatively understand why microbes growing slowly have the potential to make good use of fuel in MFCs. At the same time, slow growth does not necessarily result in speedy respiration. Alternative respirations may exist under the same growth state due to redundant pathways in the metabolic network. The big difference between the maximum and minimum respiration mainly results from the total formate secretion. With iterative flux variability analysis, a relatively ideal model of variant of G. sulfurreducens PCA was reconstructed by deleting several enzymes in the wild model, which could reach simultaneous suboptimal growth and maximum respiration. Under this ideal condition, flux towards extracellular electron transfer rather than for biosynthesis is beneficial for the conversion of organic matter to electricity without large accumulations of biomass and electricigens may maximize utilization of limited fuel. Our simulations will provide an insight into the enhanced current-generating mechanism and identify theoretical range of respiration rates for guiding strain improvement in MFCs.
Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone (LH) or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague–Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin-releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7α-methyl-nortestosterone (MENT), which is an androgen resistant to metabolism by 5α-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. 3H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igf1, Lifr, Pdgfra, Bcl2, Ccnd3 and Pcna were upregulated by MENT, and those of Pdgfra, Ccnd3 and Pcna were upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.
luteinizing hormone; progenitor Leydig cell; proliferation; testosterone
The emergence of superconductivity in the iron pnictide or cuprate high temperature superconductors usually accompanies the suppression of a long-ranged antiferromagnetic (AFM) order state in a corresponding parent compound by doping or pressurizing. A great deal of effort by doping has been made to find superconductivity in Mn-based compounds, which are thought to bridge the gap between the two families of high temperature superconductors, but the AFM order was not successfully suppressed. Here we report the first observations of the pressure-induced elimination of long-ranged AFM order at ~ 34 GPa and a crossover from an AFM insulating to an AFM metallic state at ~ 20 GPa in LaMnPO single crystals that are iso-structural to the LaFeAsO superconductor by in-situ high pressure resistance and ac susceptibility measurements. These findings are of importance to explore potential superconductivity in Mn-based compounds and to shed new light on the underlying mechanism of high temperature superconductivity.
Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen.
Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤10 years (P<0.05). Multivariate analysis confirmed that presence of other infected family member (P<0.001), low household monthly income (P = 0.003), using unsafe sources for drinking water (P = 0.003), living nearby stream/spring (P = 0.006) and living nearby pool/pond (P = 0.002) were the key factors significantly associated with schistosomiasis among these children.
This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused by schistosomiasis. Screening and treating other infected family members should also be adopted by the public health authorities in combating this infection in these communities.
Schistosomiasis remains one of the most serious and prevalent diseases worldwide. Despite intensive control efforts by the government and international bodies, schistosomiasis is the second cause of death, after malaria, in Yemen, with an estimated 3 million cases. We screened 400 children in rural areas of five provinces in Yemen for the presence of schistosomiasis. Overall, 31.8% of the children were found to be positive for schistosomiasis; 23.8% were infected by Schistosoma haematobium, and 9.3% were infected by S. mansoni. The study identified the presence of other family members infected with schistosomiasis, low household monthly income, using unsafe water supply as a source for drinking water, living nearby stream/spring and/or pool/pond as the key factors significantly associated with schistosomiasis in these communities. Innovative and integrated control measures to control this infection should be implemented among this population. Periodic school-based and community-based drug distribution, health education, provision of clean and safe drinking water, introduction of proper sanitation will help to reduce the prevalence and morbidity of schistosomiasis among these communities.
Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm, which is the first reported for any flatworm, indeed for the superphylum Lophotrochozoa. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signaling pathways for growth, development and maturation. Having a complex nervous system and a well developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteinases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.
Long non-coding RNAs (lncRNAs) as a key group of non-coding RNAs have gained widely attention. Though lncRNAs have been functionally annotated and systematic explored in higher mammals, few are under systematical identification and annotation. Owing to the expression specificity, known lncRNAs expressed in embryonic brain tissues remain still limited. Considering a large number of lncRNAs are only transcribed in brain tissues, studies of lncRNAs in developmental brain are therefore of special interest. Here, publicly available RNA-sequencing (RNA-seq) data in embryonic brain are integrated to identify thousands of embryonic brain lncRNAs by a customized pipeline. A significant proportion of novel transcripts have not been annotated by available genomic resources. The putative embryonic brain lncRNAs are shorter in length, less spliced and show less conservation than known genes. The expression of putative lncRNAs is in one tenth on average of known coding genes, while comparable with known lncRNAs. From chromatin data, putative embryonic brain lncRNAs are associated with active chromatin marks, comparable with known lncRNAs. Embryonic brain expressed lncRNAs are also indicated to have expression though not evident in adult brain. Gene Ontology analysis of putative embryonic brain lncRNAs suggests that they are associated with brain development. The putative lncRNAs are shown to be related to possible cis-regulatory roles in imprinting even themselves are deemed to be imprinted lncRNAs. Re-analysis of one knockdown data suggests that four regulators are associated with lncRNAs. Taken together, the identification and systematic analysis of putative lncRNAs would provide novel insights into uncharacterized mouse non-coding regions and the relationships with mammalian embryonic brain development.
Cerebral viscoelastic constants can be measured in a noninvasive, image-based way by magnetic resonance elastography (MRE) for the detection of neurological disorders. However, MRE brain maps of viscoelastic constants are still limited by low spatial resolution. Here we introduce three-dimensional multifrequency MRE of the brain combined with a novel reconstruction algorithm based on a model-free multifrequency inversion for calculating spatially resolved viscoelastic parameter maps of the human brain corresponding to the dynamic range of shear oscillations between 30 and 60 Hz. Maps of two viscoelastic parameters, the magnitude and the phase angle of the complex shear modulus, |G*| and φ, were obtained and normalized to group templates of 23 healthy volunteers in the age range of 22 to 72 years. This atlas of the anatomy of brain mechanics reveals a significant contrast in the stiffness parameter |G*| between different anatomical regions such as white matter (WM; 1.252±0.260 kPa), the corpus callosum genu (CCG; 1.104±0.280 kPa), the thalamus (TH; 1.058±0.208 kPa) and the head of the caudate nucleus (HCN; 0.649±0.101 kPa). φ, which is sensitive to the lossy behavior of the tissue, was in the order of CCG (1.011±0.172), TH (1.037±0.173), CN (0.906±0.257) and WM (0.854±0.169). The proposed method provides the first normalized maps of brain viscoelasticity with anatomical details in subcortical regions and provides useful background data for clinical applications of cerebral MRE.
The current investigation aimed to evaluate the transdermal potential of novel testosterone propionate (TP) ethosomes and liposomes prepared by surfactant modification. The effect of hexadecyl trimethyl ammonium bromide and cremophor EL-35 on the particle size and zeta potential of the prepared vesicles was investigated. The entrapment efficiency and stability, as well as in vitro and in vivo skin permeation, were studied with the various techniques, such as differential scanning calorimetry, confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, and so on. The results indicated that the ethosomes were defined as spherical, unilamellar structures with low polydispersity (0.100 ± 0.015) and nanometric size (156.5 ± 3.5 nm). The entrapment efficiency of TP in ethosomal and liposomal carriers was 92.7% ± 3.7% and 64.7% ± 2.1%, respectively. The stability profile of the prepared TP ethosomal system assessed for 120 days revealed very low aggregation and very low growth in vesicular size. TP ethosomes also provided an enhanced transdermal flux of 37.85 ± 2.8 μg/cm2/hour and a decreased lag time of 0.18 hours across mouse skin. The skin permeation efficiency of the TP ethosomes as further assessed by confocal laser scanning microscopy revealed enhanced permeation of rhodamine red-loaded formulations to the deeper layers of the skin (260 μm) than that of the liposomal formation (120 μm).
Testosterone propionate; surfactant-modified ethosomes; liposomes; confocal laser scanning microscopy
An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity.
The epidemic of H7N9 bird flu in eastern China in early 2013 has caused much attention from researchers as well as public health workers. The issue on modeling the transmission risks is very interesting topic. In this article, this issue is debated and discussed in order to promote further researches on prediction and prevention of avian influenza viruses supported by better interdisciplinary datasets from the surveillance and response system.
H7N9; Bird flu; Transmission; Modeling; Priorities
The discovery of cell free fetal DNA (cff-DNA) in maternal plasma has brought new insight for noninvasive prenatal diagnosis. Combining with the rapidly developed massively parallel sequencing technology, noninvasive prenatal detection of chromosome aneuploidy and single base variation has been successfully validated. However, few studies discussed the possibility of noninvasive pathogenic CNVs detection.
A novel algorithm for noninvasive prenatal detection of fetal pathogenic CNVs was firstly tested in 5 pairs of parents with heterozygote α-thalassemia of Southeast Asian (SEA) deletion using target region capture sequencing for maternal plasma. Capture probes were designed for α-globin (HBA) and β-globin (HBB) gene, as well as 4,525 SNPs selected from 22 automatic chromosomes. Mixed adaptors with 384 different barcodes were employed to construct maternal plasma DNA library for massively parallel sequencing. The signal of fetal CNVs was calculated using the relative copy ratio (RCR) of maternal plasma combined with the analysis of R-score and L-score by comparing with normal control. With mean of 101.93× maternal plasma sequencing depth for the target region, the RCR value combined with further R-score and L-score analysis showed a possible homozygous deletion in the HBA gene region for one fetus, heterozygous deletion for two fetus and normal for the other two fetus, which was consistent with that of invasive prenatal diagnosis.
Our study showed the feasibility to detect pathogenic CNVs using target region capture sequencing, which might greatly extend the scope of noninvasive prenatal diagnosis.
Many published data on the association between single nucleotide polymorphisms (SNPs) in the ESR1 gene and prostate cancer susceptibility are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of this relationship.
A literature search of PubMed, Embase, Web of Science and Chinese Biomedical (CBM) databases was conducted from their inception through July 1st, 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association.
Twelve case-control studies were included with a total 2,165 prostate cancer cases and 3,361 healthy controls. When all the eligible studies were pooled into the meta-analysis, ESR1 PvuII (C>T) and XbaI (A>G) polymorphisms showed no association with the risk of prostate cancer. However, in the stratified analyses based on ethnicity and country, the results indicated that ESR1 PvuII (C>T) polymorphism was significantly associated with increased risk of prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may significantly increase the risk of prostate cancer among American population. Furthermore, we also performed a pooled analysis for all eligible case-control studies to explore the role of codon 10 (T>C), codon 325 (C>G), codon 594 (G>A) and +261G>C polymorphisms in prostate cancer risk. Nevertheless, no significant associations between these polymorphisms and the risk of prostate cancer were observed.
Results from the current meta-analysis indicate that ESR1 PvuII (C>T) polymorphism may be a risk factor for prostate cancer among Asian populations, especially among Indian population; while ESR1 XbaI (A>G) polymorphism may increase the risk of prostate cancer among American population.
Currently very few noninvasive molecular genetic approaches are available to determine zygosity for twin pregnancies in clinical laboratories. This study aimed to develop a novel method to determine zygosity by using maternal plasma target region sequencing.
We constructed a statistic model to calculate the possibility of each zygosity type using likelihood ratios (Li) and empirical dynamic thresholds targeting at 4,524 single nucleotide polymorphisms (SNPs) loci on 22 autosomes. Then two dizygotic (DZ) twin pregnancies,two monozygotic (MZ) twin pregnancies and two singletons were recruited to evaluate the performance of our novel method. Finally we estimated the sensitivity and specificity of the model in silico under different cell-free fetal DNA (cff-DNA) concentration and sequence depth.
We obtained 8.90 Gbp sequencing data on average for six clinical samples. Two samples were classified as DZ with L values of 1.891 and 1.554, higher than the dynamic DZ cut-off values of 1.162 and 1.172, respectively. Another two samples were judged as MZ with 0.763 and 0.784 of L values, lower than the MZ cut-off values of 0.903 and 0.918. And the rest two singleton samples were regarded as MZ twins, with L values of 0.639 and 0.757, lower than the MZ cut-off values of 0.921 and 0.799. In silico, the estimated sensitivity of our noninvasive zygosity determination was 99.90% under 10% total cff-DNA concentration with 2 Gbp sequence data. As the cff-DNA concentration increased to 15%, the specificity was as high as 97% with 3.50 Gbp sequence data, much higher than 80% with 10% cff-DNA concentration.
This study presents the feasibility to noninvasively determine zygosity of twin pregnancy using target region sequencing, and illustrates the sensitivity and specificity under various detecting condition. Our method can act as an alternative approach for zygosity determination of twin pregnancies in clinical practice.