Miracle-dz/UniFAR-FTUs huggingface dataset:
Neisseria gonorrhoeae secretes chromosomal DNA via a novel type IV secretion system

The process of DNA donation for natural transformation of bacteria is poorly understood and has been assumed to involve bacterial cell death. Recently in Neisseria gonorrhoeae we found that mutations in three genes in the gonococcal genetic island (GGI) reduced the ability of a strain to act as a donor in transformation and to release DNA into the culture. To better characterize the GGI and the process of DNA donation, the 57 kb genetic island was cloned, sequenced and subjected to insertional mutagenesis. DNA sequencing revealed that the GGI has characteristics of a horizontally acquired genomic island and encodes homologues of type IV secretion system proteins. The GGI was found to be incorporated near the chromosomal replication terminus at the dif site, a sequence targeted by the site‐specific recombinase XerCD. Using a plasmid carrying a small region of the GGI and the associated dif site, we demonstrated that this model island could be integrated at the dif site in strains not carrying the GGI and was spontaneously excised from that site. Also, we were able to delete the entire 57 kb region by transformation with DNA from a strain lacking the GGI. Thus the GGI was likely acquired and integrated into the gonococcal chromosome by site‐specific recombination and may be lost by site‐specific recombination or natural transformation. We made mutations in six putative type IV secretion system genes and assayed these strains for the ability to secrete DNA. Five of the mutations greatly reduced or completely eliminated DNA secretion. Our data indicate that N. gonorrhoeae secretes DNA via a specific process. Donated DNA may be used in natural transformation, contributing to antigenic variation and the spread of antibiotic resistance, and it may modulate the host immune response.
Cyclic‐glycine‐proline accelerates mammary involution by promoting apoptosis and inhibiting IGF‐1 function

In rodents, post‐lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin‐like growth factor‐1 (IGF‐1). Overexpression of IGF‐1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic‐glycine‐proline (cGP), a metabolite of IGF‐1, normalizes IGF‐1 function under pathological conditions by regulating the bioavailability of IGF‐1. The present study investigated the effect of cGP on the physiological decline in IGF‐1 function during post‐lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post‐natal d8‐22. Before collecting tissue on post‐natal d23, a pair of mammary glands were sealed on d20 (72 hr‐engorgement, thus representative of late‐involution) and d22 (24 hr‐engorgement, thus representative of mid‐involution), while the remaining glands were allowed to involute naturally (early‐involution). During early‐involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up‐regulation of the cell survival factors, Bcl‐xl and IGF‐1R, in the early‐involution cGP glands compared with the control glands. During late‐involution, cGP reduced the bioactivity of IGF‐1, which was evident through decreased phosphorylation of IGF‐1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early‐, peak‐, or late‐stage of lactation. These data show that cGP accelerates post‐lactational involution by promoting apoptosis and the physiological decline in IGF‐1 function.
PTEN Signaling pathways in glioblastoma

Malignant gliomas are the most common primary brain tumor in adults, but the prognosis for patients with these tumors remains poor despite advances in diagnosis and standard therapies such as surgery, radiation therapy, and chemotherapy. Progress in the treatment of gliomas now depends to a great extent on an increased understanding of the biology of these tumors. Recent insights into the biology of gliomas include the finding that tyrosine kinase receptors and signal transduction pathways play a role in tumor initiation and maintenance. Deregulation of phosphatidylinositol 3-kinase (PI3K) signaling pathways resulting from genetic alterations in the PTEN tumor suppressor gene on 10q23 at the level of LOH, mutation and methylation have been identified in at least 60% of glioblastoma. Loss of PTEN function by mutation or LOH correlates with poor survival in anaplastic astrocytoma and glioblastoma, suggesting that PTEN plays a role in patient outcome. Interestingly, amplification of Epidermal growth factor receptor (EGFR) in the background of heterozygous PTEN knockout mice develop invasive glioma very similar to human glioblastoma, demonstrating the importance of PTEN in glioma progression and providing a model system to evaluate the efficacy of targeting PTEN in glioblastoma.
MEK/ERK‐dependent uPAR expression is required for motility via phosphorylation of P70S6K in human hepatocarcinoma cells

Motility and invasiveness events require specific intracellular signaling cascade activations. In cancer liver cells, one of these mechanisms could involve the MAPK MEK/ERK cascade activation which has been shown over expressed and activated in hepatocellular carcinoma. To study whether the MEK/ERK cascade is involved in the motility of HCC, we examined the effect of MEK inhibitor and ERK2 silencing using monolayer wound‐healing assays and fluoroblock invasion systems. Evidence was provided that the MAPK cascade is a key transduction pathway which controls HCC cells motility and invasiveness. We could disconnect proliferation to motility using mitomycin C and we established that RNAi‐mediated inhibition of ERK2 led to strongly reduced cell motility. To improve our understanding, we analysed the regulation and the role of urokinase receptor (uPAR) in this process. We provided evidence that uPAR was under a MEK/ERK dependent mechanism and blocking uPAR activity using specific antagonist or inhibiting its expression by RNA interference which resulted in complete inhibition of motility. Moreover, we found in MAPK inhibited cultures and in uPAR silencing cells that p70S6K phosphorylation on residue Thr‐389 was significantly reduced, whereas Ser‐421/Thr‐424 phosphorylation did not change. We highlighted that the FRAP/mTOR pathway did not affect motility and Thr‐389 phosphorylation. Furthermore, we demonstrated that p70S6K inhibition by RNA interference completely inhibited hepatocarcinoma cell motility. Therefore, targeting uPAR and/or MEK/ERK/S6K by RNA interference could be a major therapeutic strategy for the future treatment of invasive hepatocarcinoma cells. J. Cell. Physiol. 212: 526–536, 2007. © 2007 Wiley‐Liss, Inc.
AUV integrated navigation algorithm based on single beacon ranging

When the inertial navigation system is positioning underwater vehicle such as the AUV, it can be achieved without any outside information, and be real-time and autonomy for AUV navigation. It can navigate the AUV real-timely and independently without the help of any outside information. However, the positioning accuracy will reduce with the increasing cumulative error when the inertial navigation system working for a long time. Aiming at this problem, this paper presents a solution model based on the principle of indirect adjustment, using the single beacon ranging information, heading angle information and velocity information as the observation information. The theoretical deduction formula and the positioning accuracy analysis of the undetermined target are given. According to the method for solving the undetermined target as the true value, and reflect the positioning error correction. Using the undetermined target attained from the method as the true value to reflect the positioning error correction. The simulation results show that using single — beacon navigation based on indirect adjustment can effectively suppress the cumulative error caused by inertial navigation and achieve higher positioning accuracy.
Breast Cancer Blood Flow and Metabolism on Dual-Acquisition 18F-FDG PET: Correlation with Tumor Phenotype and Neoadjuvant Chemotherapy Response

Early changes in tumor glucose metabolism (SUVmax) and in tumor blood flow (BF) have been evaluated separately for monitoring breast cancer response to neoadjuvant chemotherapy (NAC). This study used a single 18F-FDG dual-acquisition PET examination to simultaneously assess these two imaging features and to determine whether they correlate with the same pretherapy tumor phenotypic features and whether they are comparable or complementary in predicting pathologic complete response (pCR). Methods: This prospective study included 150 women with breast cancer and an indication for NAC. A 2-min chest-centered dynamic PET acquisition was performed at the time of 18F-FDG injection, followed by a delayed static PET acquisition 90 min later. Tumor BF was calculated from the dynamic acquisition using a validated first-pass model, and tumor SUVmax was calculated from the delayed acquisition. This dual acquisition was repeated after the first cycle of NAC to measure early changes in tumor BF and SUVmax. Results: A weak correlation was found between SUVmax and BF at baseline (r = 0.22; P = 0.006). A high baseline SUVmax was associated with all biologic markers of tumor aggressiveness, including the triple-negative breast cancer subtype (P < 0.0001). In contrast, a high baseline BF was associated only with obesity (P = 0.002). The change in SUVmax (mean, −44.6% ± 27.4%) varied depending on the Scarff–Bloom–Richardson grade, overexpression of human epidermal growth factor receptor 2 (HER2-positive), and lack of hormone receptor expression (P = 0.04, P < 0.001, and P = 0.01, respectively). BF (mean change, −26.9% ± 54.3%) showed a drastic reduction only in HER2-positive subtypes (−58.7% ± 30.0%), supporting the antiangiogenic effect of trastuzumab. Changes in SUVmax outperformed changes in BF for predicting pCR in all tumor subtypes: the areas under the curve for change in SUVmax were 0.82, 0.65, and 0.90 in the triple-negative, HER2-positive, and luminal subtypes, respectively. Conclusion: Of the two biologic hallmarks of cancer evaluated in this study, a reduction in tumor glucose metabolism was more accurate than a reduction in tumor BF for predicting pCR in the different subtypes of breast cancer.
The Impact of Pre‐Operative Loco‐Regional Therapy on Outcome After Liver Transplantation for Hepatocellular Carcinoma

No prior studies have shown that pre‐operative loco‐regional therapy for hepatocellular carcinoma (HCC) improves survival following orthotopic liver transplantation (OLT). We performed subgroup analyses according to pathologic HCC stage among 168 patients who underwent OLT to test the hypothesis that pre‐operative loco‐regional therapy confers a survival advantage in a subgroup at intermediate risk for HCC recurrence. Patients with pathologic T3 HCC meeting the proposed UCSF expanded criteria (single lesion not exceeding 6.5 cm or two to three lesions none > 4.5 cm with total tumor diameter within 8 cm) had a similar 5‐year recurrence‐free survival as patients with pathologic T2 HCC (88.5% vs. 93.8%; p = 0.56). In the subgroup with pathologic T2 or T3 HCC, the 5‐year recurrence‐free survival was 93.8% for the 85 patients who received pre‐operative loco‐regional therapy, versus 80.6% for the other 41 patients without treatment (p = 0.049). The treatment benefit, according to 5‐year recurrence‐free survival, appeared greater for pathologic T3 (85.9% vs. 51.4%; p = 0.05) than T2 HCC (96.4% versus 87.1%; p = 0.12). In conclusion, although the lack of a randomized controlled design precludes drawing firm conclusions, our results suggest that pre‐operative loco‐regional therapy may confer a survival benefit after OLT in the subgroup with pathologic T2 and T3 HCC.
Do borrowers make homogeneous decisions in online P2P lending market? An empirical study of PPDai in China

In online P2P lending market, borrowers need to make strategic decisions, which will determine they will get the loans or not. In this study, we firstly investigate what and how the decisions made by borrowers influence the auction results. The empirical results display that borrower' decisions, e.g., loan amount, interest rate will determine whether she could successfully fund loan or not, especially loan amount requested by borrowers. Then, it is focus on analyzing the difference of two borrower's critical decisions (loan amount and interest rate) among successful, unsuccessful capable and incapable listings, and find out that borrowers of three types of listings make heterogeneous decisions. Finally, we provide some suggestions to online P2P lending market about borrowers' decisions aid services based on the results, which could be a contribution with the practical implementation of borrower decision support system.
Maternal and neonatal outcomes after induction of labor without an identified indication.

OBJECTIVE This study was undertaken to examine associations between induction of labor and maternal and neonatal outcomes among women without an identified indication for induction. STUDY DESIGN This was a population-based cohort study of 2886 women with induced labor and 9648 women with spontaneous labor who were delivered at 37 to 41 weeks' gestation, all without identified medical and obstetric indications for induction. RESULTS Among nulliparous women 19% of women with induced labor versus 10% of those with spontaneous labor underwent cesarean delivery (adjusted relative risk, 1.77; 95% confidence interval, 1.50-2.08). No association was seen in multiparous women (relative risk, 1.07; 95% confidence interval, 0. 81-1.39). Among all women induction was associated with modest increases in instrumental delivery (19% vs 15%; relative risk, 1.20; 95% confidence interval, 1.09-1.32) and shoulder dystocia (3.0% vs 1. 7%; relative risk, 1.32; 95% confidence interval, 1.02-1.69). CONCLUSION Among women who lacked an identified indication for induction of labor, induction was associated with increased likelihood of cesarean delivery for nulliparous but not multiparous women and with modest increases in the risk of instrumental delivery and shoulder dystocia for all women.
Neuregulin-1 potentiates agrin-induced acetylcholine receptor clustering through muscle-specific kinase phosphorylation

At neuromuscular synapses, neural agrin (n-agrin) stabilizes embryonic postsynaptic acetylcholine receptor (AChR) clusters by signalling through the muscle-specific kinase (MuSK) complex. Live imaging of cultured myotubes showed that the formation and disassembly of primitive AChR clusters is a dynamic and reversible process favoured by n-agrin, and possibly other synaptic signals. Neuregulin-1 is a growth factor that can act through muscle ErbB receptor kinases to enhance synaptic gene transcription. Recent studies suggest that neuregulin-1–ErbB signalling can modulate n-agrin-induced AChR clustering independently of its effects on transcription. Here we report that neuregulin-1 increased the size of developing AChR clusters when injected into muscles of embryonic mice. We investigated this phenomenon using cultured myotubes, and found that in the ongoing presence of n-agrin, neuregulin-1 potentiates AChR clustering by increasing the tyrosine phosphorylation of MuSK. This potentiation could be blocked by inhibiting Shp2, a postsynaptic tyrosine phosphatase known to modulate the activity of MuSK. Our results provide new evidence that neuregulin-1 modulates the signaling activity of MuSK and hence might function as a second-order regulator of postsynaptic AChR clustering at the neuromuscular synapse. Thus two classic synaptic signalling systems (neuregulin-1 and n-agrin) converge upon MuSK to regulate postsynaptic differentiation.
Explorer On the Genetic Interpretation of Disease Data

Background: The understanding of host genetic variation in disease resistance increasingly requires the use of field data to obtain sufficient numbers of phenotypes. We introduce concepts necessary for a genetic interpretation of field disease data, for diseases caused by microparasites such as bacteria or viruses. Our focus is on variance component estimation and we introduce epidemiological concepts to quantitative genetics. Methodology/Principal Findings: We have derived simple deterministic formulae to predict the impacts of incomplete exposure to infection, or imperfect diagnostic test sensitivity and specificity on heritabilities for disease resistance. We show that these factors all reduce the estimable heritabilities. The impacts of incomplete exposure depend on disease prevalence but are relatively linear with the exposure probability. For prevalences less than 0.5, imperfect diagnostic test sensitivity results in a small underestimation of heritability, whereas imperfect specificity leads to a much greater underestimation, with the impact increasing as prevalence declines. These impacts are reversed for prevalences greater than 0.5. Incomplete data recording in which infected or diseased individuals are not observed, e.g. data recording for too short a period, has impacts analogous to imperfect sensitivity. Conclusions/Significance: These results help to explain the often low disease resistance heritabilities observed under field conditions. They also demonstrate that incomplete exposure to infection, or suboptimal diagnoses, are not fatal flaws for demonstrating host genetic differences in resistance, they merely reduce the power of datasets. Lastly, they provide a tool for inferring the true extent of genetic variation in disease resistance given knowledge of the disease biology. Citation: Bishop SC, Woolliams JA (2010) On the Genetic Interpretation of Disease Data. PLoS ONE 5(1): e8940. doi:10.1371/journal.pone. 0008940 Editor: Syed A. Aziz, Health Canada, Canada Received September 8, 2009; Accepted November 3, 2009; Published January 28, 2010 Copyright: 2010 Bishop, Woolliams. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors were funded by the Biotechnology and Biological Sciences Research Council (BBSRC), via The Roslin Institute’s Institute Strategic Programme Grant (ISPG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: S.C. B. has on one occasion served as an academic editor (08-PONE-RA-04516) for a Plos One paper. * E-mail: Stephen.Bishop@roslin.ed.ac.uk
srfA is an operon required for surfactin production, competence development, and efficient sporulation in Bacillus subtilis

The srfA locus of Bacillus subtilis is defined by a transposon Tn917 insertion and is required for production of the peptide secondary metabolite surfactin. The srfA locus was isolated by cloning the DNA flanking srfA::Tn917 insertions followed by chromosome walking. The cloned region is an operon of over 25 kb which covers the transcription initiation region but not the intact 3' end of srfA. csh-293, which was previously identified as a Tn917lac mutation that impairs competence development and causes a conditional defect in sporulation, was known to be located in the vicinity of the srfA locus within the B. subtilis genome. The csh-293::Tn917lac mutation was discovered to cause a defect in surfactin production and was shown to be located in the srfA operon by its cotransformation with srfA mutations and by Southern hybridization analysis. Insertion mutations in srfA, created by the chromosomal integration of plasmids bearing overlapping srfA DNA fragments, were examined for their effects on surfactin production, competence, and sporulation. All three processes were found to require the intact 5' half of the srfA operon, whereas the 3' half of srfA was found to be required for sporulation and surfactin production but not competence. These experiments show that srfA gene products function in B. subtilis cell specialization and differentiation.
Gallstone Disease in North India: Clinical and Ultrasound Profile in a Referral Hospital

We studied the prevalence of gallstones in patients with upper abdominal pain, heaviness, or discomfort by ultrasound examination of the gallbladder. The actual ultrasound examination was performed by a clinical gastroenterologist blinded to the symptoms. Of 1,680 consecutive dyspeptic patients, 500 (29.8%) had gallstones. The gallbladder was contracted in 450 (91.2%), normal-size in 36 (7.2%), and distended in 8 (1.6%). Biliary colic was more frequently the presenting complaint in patients with a contracted gallbladder than in those with normal size gallbladder (p < 0.001). Dyspepsia was more frequent in the presence of a normal size gallbladder than a contracted one (p < 0.001). We conclude that ultrasonography of the gallbladder by the clinician has a high diagnostic yield, and the symptom complex has an excellent correlation with the sonographic appearance.
A review of teriparatide and its clinical efficacy in the treatment of osteoporosis

Until recently, antiresorptive medications such as bisphosphonates and raloxifene represented the main pharmacological treatment options for patients with osteoporosis. With the introduction of teriparatide (rhPTH(1–34)), a recombinant formulation of parathyroid hormone (PTH) consisting of the first 34 amino acids of the N-terminal region, bone-forming therapy has now become possible. Preclinical, as well as human studies, have shown increases in trabecular as well as cortical bone mass with subsequent improvements in bone microstructure and cortical thickness. The subcutaneous daily dose of teriparatide 20 μg has been shown to decrease the occurrence of new vertebral fractures in caucasian women (70 years of age) by 65%, in a large randomised, double-blind placebo-controlled trial. Moderate-to-severe fractures or multiple vertebral fractures could be reduced by 90 and 77%, respectively. There was also a significant beneficial effect on new nonvertebral fractures (-35%) by the end of the 21-month treatment period. The reduction in nonvertebral fractures became evident after ∼ 8 – 12 months of treatment. Smaller studies in men with low bone mass showed similar effects on bone mineral density and changes in bone turnover markers when compared to the results obtained in postmenopausal women. Recent data suggest that teriparatide is best given as monotherapy and not in combination with a bisphosphonate. Previous bisphosphonate treatment is also likely to diminish the bone anabolic potential of teriparatide. In order to preserve bone mass gained during the recommended 18- to 24-month treatment period, antiresorptive medication should be prescribed following teriparatide treatment. Studies so far have not shown serious PTH-related side effects. Hypercalcaemia is usually mild and transient and the osteosarcoma risk reported in rat toxicology studies is very unlikely to be predictive of a similar risk in humans. As teriparatide is expensive, its use at the moment should be limited to patients with more severe forms of osteoporosis, usually with the presence or history of one or more fractures because of those patients’ high risk for subsequent fractures.