Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversification of Schistosoma japonicum in Mainland China Revealed by Mitochondrial DNA

Background Schistosoma japonicum still causes severe parasitic disease in mainland China, but mainly in areas along the Yangtze River. However, the genetic diversity in populations of S. japonicum has not been well understood across its geographical distribution, and such data may provide insights into the epidemiology and possible control strategies for schistosomiasis. Methodology/Principal Findings In this study infected Oncomelania snails were collected from areas in the middle and lower (ML) reaches of the Yangtze River, including Hubei, Hunan, Anhui, Jiangxi and Jiangsu provinces, and in the upper reaches of the river, including Sichuan and Yunnan provinces in southwest (SW) China. The adult parasites obtained from experimentally infected mice using isolated cercariae were sequenced individually for several fragments of mitochondrial regions, including Cytb-ND4L-ND4, 16S-12S and ND1. Populations in the ML reaches exhibited a relatively high level of diversity in nucleotides and haplotypes, whereas a low level was observed for populations in the SW, using either each single fragment or the combined sequence of the three fragments. Pairwise analyses of F-statistics (Fst) revealed a significant genetic difference between populations in the ML reaches and those in the SW, with limited gene flow and no shared haplotypes in between. It is rather obvious that genetic diversity in the populations of S. japonicum was significantly correlated with the geographical distance, and the geographical separation/isolation was considered to be the major factor accounting for the observed difference between populations in the ML reaches and those in the SW in China. Conclusions S. japonicum in mainland China exhibits a high degree of genetic diversity, with a similar pattern of genetic diversity as observed in the intermediate host snails in the same region in China.
Mutations in the MutSα interaction interface of MLH1 can abolish DNA mismatch repair

MutLα, a heterodimer of MLH1 and PMS2, plays a central role in human DNA mismatch repair. It interacts ATP-dependently with the mismatch detector MutSα and assembles and controls further repair enzymes. We tested if the interaction of MutLα with DNA-bound MutSα is impaired by cancer-associated mutations in MLH1, and identified one mutation (Ala128Pro) which abolished interaction as well as mismatch repair activity. Further examinations revealed three more residues whose mutation interfered with interaction. Homology modelling of MLH1 showed that all residues clustered in a small accessible surface patch, suggesting that the major interaction interface of MutLα for MutSα is located on the edge of an extensive β-sheet that backs the MLH1 ATP binding pocket. Bioinformatic analysis confirmed that this patch corresponds to a conserved potential protein–protein interaction interface which is present in both human MLH1 and its E.coli homologue MutL. MutL could be site-specifically crosslinked to MutS from this patch, confirming that the bacterial MutL–MutS complex is established by the corresponding interface in MutL. This is the first study that identifies the conserved major MutLα–MutSα interaction interface in MLH1 and demonstrates that mutations in this interface can affect interaction and mismatch repair, and thereby can also contribute to cancer development.
Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots

For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the δ-band activity is much less recurrent than α-band activity. Moreover, α-activity is susceptible to pre-stimuli, while δ-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain.
Adjuvant Therapy With Sodium Alendronate for the Treatment of Experimental Periodontitis in Rats.

BACKGROUND This study assesses the effects of topical sodium alendronate (SA) as an adjuvant to the mechanical treatment of ligature-induced periodontitis in rats. METHODS Ninety animals were subjected to the induction of periodontitis via the installation of a ligature around the mandibular left first molar. After 7 days, the ligature was removed, and the animals were distributed into the following groups: 1) NT group (n = 30), no treatment; 2) SRP group (n = 30), scaling and root planing (SRP) and local irrigation with physiologic saline solution; and 3) SRP/SA group (n = 30), SRP and local irrigation with SA (10(-5) M). Ten animals from each group were euthanized at 7, 15, and 30 days after treatment. Histologic and histometric analyses were performed in the furcation region. The percentage of bone in the furcation (PBF) was measured. Immunohistochemical analyses for detecting the receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and activated caspase-3 were performed at the furcation region. RESULTS Compared with the other groups, the SRP/SA group showed less local inflammation and better tissue reparation during the entire experiment. There was more PBF in the SRP/SA group than in the other groups at days 7 and 15. Stronger OPG immunolabeling and weaker RANKL immunolabeling were observed in the SRP/SA group at 15 and 30 days. There were fewer TRAP-positive cells in the SRP/SA group than in the NT group at all of the time points. There was no difference in the number of activated caspase-3-positive osteocytes among groups and time points. CONCLUSION It can be concluded that topical use of SA as an adjuvant to SRP is effective in the treatment of experimental periodontitis.
Regulation of Rat Hepatic L-Pyruvate Kinase Promoter Composition and Activity by Glucose, n-3 Polyunsaturated Fatty Acids, and Peroxisome Proliferator-activated Receptor-α Agonist*

Carbohydrate regulatory element-binding protein (ChREBP), MAX-like factor X (MLX), and hepatic nuclear factor-4α (HNF-4α) are key transcription factors involved in the glucose-mediated induction of hepatic L-type pyruvate kinase (L-PK) gene transcription. n-3 polyunsaturated fatty acids (PUFA) and WY14643 (peroxisome proliferator-activated receptor α (PPARα) agonist) interfere with glucose-stimulated L-PK gene transcription in vivo and in rat primary hepatocytes. Feeding rats a diet containing n-3 PUFA or WY14643 suppressed hepatic mRNAL-PK but did not suppress hepatic ChREBP or HNF-4α nuclear abundance. Hepatic MLX nuclear abundance, however, was suppressed by n-3 PUFA but not WY14643. In rat primary hepatocytes, glucose-stimulated accumulation of mRNALPK and L-PK promoter activity correlated with increased ChREBP nuclear abundance. This treatment also increased L-PK promoter occupancy by RNA polymerase II (RNA pol II), acetylated histone H3 (Ac-H3), and acetylated histone H4 (Ac-H4) but did not significantly impact L-PK promoter occupancy by ChREBP or HNF-4α. Inhibition of L-PK promoter activity by n-3 PUFA correlated with suppressed RNA pol II, Ac-H3, and Ac-H4 occupancy on the L-PK promoter. Although n-3 PUFA transiently suppressed ChREBP and MLX nuclear abundance, this treatment did not impact ChREBP-LPK promoter interaction. HNF4α-LPK promoter interaction was transiently suppressed by n-3 PUFA. Inhibition of L-PK promoter activity by WY14643 correlated with a transient decline in ChREBP nuclear abundance and decreased Ac-H4 interaction with the L-PK promoter. WY14643, however, had no impact on MLX nuclear abundance or HNF4α-LPK promoter interaction. Although overexpressed ChREBP or HNF-4α did not relieve n-3 PUFA suppression of L-PK gene expression, overexpressed MLX fully abrogated n-3 PUFA suppression of L-PK promoter activity and mRNAL-PK abundance. Overexpressed ChREBP, but not MLX, relieved the WY14643 inhibition of L-PK. In conclusion, n-3 PUFA and WY14643/PPARα target different transcription factors to control L-PK gene transcription. MLX, the heterodimer partner for ChREBP, has emerged as a novel target for n-3 PUFA regulation.
WHAT THE HASHTAG?

Twitter is the latest social networking tool said to be reshaping politics. Twitter allows subscribers to write a 140-character status update, called a ‘tweet'. This research analyzes the intersection of microblogging and Canadian politics. There is little scholarship on the political aspects of Twitter. This paper seeks to fill this gap through a content analysis of the most popular Canadian political hashtag, #cdnpoli. Designated by a ‘hash' symbol (#), a hashtag is a keyword assigned to information that describes a tweet and aides in searching. With 50 million tweets per day, hashtags are central to organizing information on Twitter. Hashtags organize discussion around specific topics or events. Political hashtags came to prominence in events like the 2009 Iran presidential election. Indeed, #iranelection was the number one news topic on Twitter in 2009. The popular literature suggests that Twitter is a democratic media because it allows for on-the-ground reporting of breaking news and democratic activism. This analysis shows that informing is the primary function of a political hashtag such as #cdnpoli. Political dialogue and reporting is rare. Contributors scour the internet for relevant online information on Canadian politics and use #cdnpoli as a dissemination feed. The value of a political hashtag derives from the real-time nature of the information shared.
Violence and gender relations: Theories and interventions.

Introduction - Barbara Fawcett et al PART ONE: CURRENT ISSUES AND DEBATES Women and Violence - Jalna Hanmer Commonalities and Diversities Men's Violence to Known Women - Jeff Hearn Historical, Everyday and Theoretical Constructions by Men PART TWO: GENDERED ORGANIZATIONS The Organization(s) of Violence - Jeff Hearn Gender, Violence and Social Work Organizations - Elizabeth Harlow Gender and Power in Organizations - Wendy Hollway Women, Mental Health and Community Care - Barbara Fawcett An Abusive Combination? PART THREE: THE PROBLEM OF MEN'S VIOLENCE Men's Violence to Known Women - Jeff Hearn Men's Accounts and Men's Policy Developments Men's Resistance to Social Workers - Judith Milner Working with Men Who Sexually Abuse Children - Elizabeth Lancaster The Experience of the Probation Service PART FOUR: GENERATION AND GENDER Violence, Gender and Elder Abuse - Terri Whittaker Organized Abuse - Brid Featherstone and Elizabeth Harlow Themes and Issues Issues of Race and Culture in Child Abuse - Melody Mtezuka Victims or Villains? Women Who Physically Abuse Their Children - Brid Featherstone
Cerebrospinal Fluid Alzheimer's Disease Biomarkers Across the Spectrum of Lewy Body Diseases: Results from a Large Multicenter Cohort.

BACKGROUND Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers. OBJECTIVE We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB). METHODS We included 375 DLB patients, 164 Parkinson's disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau. RESULTS A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF. CONCLUSION A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.
Small Molecule Therapeutics Antiproliferative Effects of CDK 4 / 6 Inhibition in CDK 4-Ampli fi ed Human Liposarcoma In Vitro and In Vivo

Well-differentiated/dedifferentiated liposarcomas (WD/DDLPS) are among themost common subtypes of soft tissue sarcomas. Conventional systemic chemotherapy has limited efficacy and novel therapeutic strategies are needed to achieve better outcomes for patients. The cyclin-dependent kinase 4 (CDK4) gene is highly amplified in more than 95% of WD/DDLPS. In this study, we explored the role of CDK4 and the effects of NVP-LEE011 (LEE011), a novel selective inhibitor of CDK4/CDK6, on a panel of human liposarcoma cell lines and primary tumor xenografts. We found that both CDK4 knockdown by siRNA and inhibition by LEE011 diminished retinoblastoma (RB) phosphorylation and dramatically decreased liposarcoma cell growth. Cell-cycle analysis demonstrated arrest at G0–G1. siRNA-mediated knockdown of RB rescued the inhibitory effects of LEE011, demonstrating that LEE011 decreased proliferation through RB. Oral administration of LEE011 to mice bearing human liposarcoma xenografts resulted in approximately 50% reduction in tumor F-fluorodeoxyglucose uptake with decreased tumor biomarkers, including RB phosphorylation and bromodeoxyuridine incorporation in vivo. Continued treatment inhibited tumor growth or induced regression without detrimental effects on mouse weight. After prolonged continuous dosing, reestablishment of RB phosphorylation and cell-cycle progression was noted. These findings validate the critical role of CDK4 in maintaining liposarcoma proliferation through its ability to inactivate RB function, and suggest its potential function in the regulation of survival and metabolism of liposarcoma, supporting the rationale for clinical development of LEE011 for the treatment of WD/DDLPS. Mol Cancer Ther; 13(9); 2184–93. 2014 AACR.
Opioids Depress Cortical Centers Responsible for the Volitional Control of Respiration

Respiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensory-affective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem.
A novel gammaretroviral shuttle vector insertional mutagenesis screen identifies SHARPIN as a breast cancer metastasis gene and prognostic biomarker

Breast cancer (BC) is the second leading cause of malignancy among U.S. women. Metastasis results in a poor prognosis and increased mortality, but the molecular mechanisms by which metastatic tumors occur are not well understood. Identifying the genes that drive the metastatic process could provide targets for improved therapy and biomarkers to improve BC patient outcomes. Using a forward mutagenesis screen, BC cells mutagenized with a replication-incompetent gammaretroviral vector (γRV) were xenotransplanted into the mammary fat pad of immunodeficient mice. In this approach the vector provirus dysregulates nearby genes, providing a selective advantage to transduced cells to form metastases. Metastatic tumors were analyzed for proviral integration sites to identify nearby candidate metastasis genes. The γRV has a transgene cassette that allows for rescue in bacteria and rapid identification of vector integration sites. Using this approach, we identified the previously described metastasis gene WWTR1 (TAZ), and three other novel candidate metastasis genes including SHARPIN. SHARPIN was independently validated in vivo as a BC metastasis gene. Analysis of patient data showed that SHARPIN expression predicts metastasis-free survival after adjuvant therapy. Our approach has broad potential to identify genes involved in oncogenic processes for BC and other cancers. We show here it can identify both known (WWTR1) and novel (SHARPIN) BC metastasis genes.
ON THE WORST-CASE CONVERGENCE OF MR AND CG FOR SYMMETRIC POSITIVE DEFINITE TRIDIAGONAL TOEPLITZ MATRICES

We study the convergence of the minimal residual (MR) and the conjugate gradient (CG) method when applied to linear algebraic systems with symmetric positive definite tridiagonal Toeplitz matrices. Such systems arise, for example, from the discretization of one-dimensional reaction-diffusion equations with Dirichlet boundary conditions. Based on our previous results in [J. Liesen and P. Tichý, BIT, 44 (2004), pp. 79–98], we concentrate on the next-to-last iteration step, and determine the initial residuals and initial errors for the MR and CG method, respectively, that lead to the slowest possible convergence. By this we mean that the methods have made the least possible progress in the next-to-last iteration step. Using these worst-case initial vectors, we discuss which source term and boundary condition in the underlying reaction-diffusion equation are the worst in the sense that they lead to the worst-case initial vectors for the MR and CG methods. Moreover, we determine (or very tightly estimate) the worst-case convergence quantities in the next-to-last step, and compare these to the convergence quantities obtained from average (or unbiased) initial vectors. The spectral structure of the considered matrices allows us to apply our worst-case results for the next-to-last step to derive worst-case bounds also for other iteration steps. We present a comparison of the worst-case convergence quantities with the classical convergence bound based on the condition number of , and finally we discuss the MR and CG convergence for the special case of the one-dimensional Poisson equation with Dirichlet boundary conditions.
Evaluation of Peptide Nucleic Acid Probe-based Real-time PCR for Detection of Mycobacterium tuberculosis Complex and Nontuberculous Mycobacteria in Respiratory Specimens

Background A peptide nucleic acid (PNA) probe-based real-time PCR (PNAqPCR™ TB/NTM detection kit; PANAGENE, Korea) assay has been recently developed for the simultaneous detection of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) in clinical specimens. The study was aimed at evaluation of the performance of PNA probe-based real-time PCR in respiratory specimens. Methods To evaluate potential cross-reactivity, the extracted DNA specimens from Mycobacterium species and non-mycobacterial species were tested using PNA probe-based real-time PCR assay. A total of 531 respiratory specimens (482 sputum specimens and 49 bronchoalveolar washing fluid specimens) were collected from 230 patients in July and August, 2011. All specimens were analyzed for the detection of mycobacteria by direct smear examination, mycobacterial culture, and PNA probe-based real-time PCR assay. Results In cross-reactivity tests, no false-positive or false-negative results were evident. When the culture method was used as the gold standard test for comparison, PNA probe-based real-time PCR assay for detection of MTBC had a sensitivity and specificity of 96.7% (58/60) and 99.6% (469/471), respectively. Assuming the combination of culture and clinical diagnosis as the standard, the sensitivity and specificity of the new real-time PCR assay for detection of MTBC were 90.6% (58/64) and 99.6% (465/467), respectively. The new real-time PCR for the detection of NTM had a sensitivity and specificity of 69.0% (29/42) and 100% (489/489), respectively. Conclusions The new real-time PCR assay may be useful for the detection of MTBC in respiratory specimens and for discrimination of NTM from MTBC.
Parental Occupation and Neural Tube Defect–Affected Pregnancies Among Mexican Americans

In a case–control study, we examined whether parental occupational exposures were related to neural tube defect (NTD)–affected pregnancies among Mexican Americans living along the Texas–Mexico border. Case women were 184 Mexican-American women with NTD-affected pregnancies; control women were 225 study-area residents who delivered normal babies during the same period as the case women. The women were interviewed in person about maternal and paternal occupations and work exposures during the periconceptional period. Compared with control women, case women were more likely to have had occupational exposures to solvents (odds ratio [OR], ∞; 95% confidence interval [CI], 2.4−∞) and also were more likely to have worked in cleaning (OR 9.5; 95% CI, 1.1 to 82.2) or health care occupations (OR 3.0; 95% CI, 1.0 to 9.0) than control women. No compelling associations were found between paternal work exposures or occupations and NTDs in offspring in this population.
Bronchial wheezing predicts inflammation and respiratory failure in fire smoke victims

Acute fire smoke inhalation injury involves inflammatory mediators whose roles are poorly understood. We carried out a prospective observational study of fire smoke victims to identify clinical and biochemical markers that may predict pulmonary dysfunction and investigated possible correlations between dysfunction and cytokines in bronchoalveolar lavage (BAL) fluid and blood.