Miracle-dz/UniFAR-FTUs huggingface dataset:
MATERNAL-FETAL DISPOSITION OF BISPHENOL A IN PREGNANT SPRAGUE-DAWLEY RATS

This study describes the maternal-fetal disposition of bisphenol A and its distribution into the placenta and amniotic fluid after iv injection (2 mg/kg) to pregnant Sprague-Dawley rats. Bisphenol A was distributed extensively to the placenta and fetus, with their respective AUC values 4.4- and 2.2-fold greater than AUC for the maternal serum. In contrast, the distribution of bisphenol A into the amniotic fluid was low, with the mean amniotic fluid-to-maternal serum AUC ratio of 0.2. The decay curves of bisphenol A in the placenta, fetus, and amniotic fluid paralleled that of the maternal serum during the terminal elimination phase. A five-compartment open model consisting of the maternal central, maternal peripheral, placental, fetal, and amniotic fluid compartments was used to describe the disposition of bisphenol A in pregnant rats, with the elimination occurring from the maternal central and fetal compartments. Based on this model, bisphenol A delivered to the placenta was transferred primarily to the fetus [ k pf /( k pf + k pc + k pa ) = 65.4%], with the remaining fraction transported to the maternal central (33.2%) and amniotic fluid (1.4%) compartments. Bisphenol A was eliminated from the amniotic fluid by the fetal (63.9%) and placental (36.1%) routes. On the other hand, bisphenol A was eliminated from the fetus primarily by the placental route back to mother [ k fp /( k fp + k fa + k fo ) = 100%], with the amniotic route playing an insignificant role in fetal elimination. The percent contribution of the fetal elimination to the total elimination in the maternal-fetal unit was 0.05% [CL fo AUC fetus /(CL co AUC maternal serum + CL fo AUC fetus )]. The pharmacokinetic model used in this study provides insights into the routes of elimination of bisphenol A in the maternal-fetal rat upon maternal administration.
Assessment of circulating serum DNA integrity in colorectal cancer patients.

UNLABELLED Background /Aim: Studies evaluating the integrity of cell-fee DNA (cfDNA) in colorectal cancer (CRC) have led to inconsistent results. Herein, we analyzed the utility of two different DNA integrity indexes (ACTB(384)/ACTB(106) and ALU(247)/ALU(115)) to assess cfDNA fragmentation in Turkish CRC patients. The correlation of circulating nucleosomes (cNUC) with the fragment sizes was also evaluated. MATERIALS AND METHODS Seventy two CRC patients and 42 CRC-free control individuals were enrolled in the study. cfDNA was analyzed by quantitative polymerase chain reaction (qPCR). RESULTS While with ALU(247)/ALU(115)there was a small difference between the groups, an approximately 3-fold (median values=0.12 and 0.34) lower integrity was found in the patients using the ACTB(384)/ACTB(106) ratio (p=0.06). The correlation between cNUC and qPCR threshold cycles was much higher for shorter fragments. CONCLUSION Lower DNA integrity and the predominance of mononuclesomes in serum reveal high fragmentation of cfDNA in CRC patients.
The Effect of Maternal Hypothyroidism on the Carbohydrate Metabolism and Insulin Secretion of Isolated Islets in Adult Male Offspring of Rats

Thyroid hormones have crucial developmental effect during fetal life. This study investigates the effects of maternal hypothyroidism on the carbohydrate metabolism and insulin secretion capacity of islets of the adult male offspring of rats. One group of pregnant mothers (fetal hypothyroid) of Wistar rats drank water containing 0.02% of 6-propyl-2-thiouracil during pregnancy, while the control group consumed only tap water. After delivery, survival and weight of the neonates from both groups were followed. In adult male offspring, the intravenous glucose tolerance test was performed and 5-6 weeks later, glucose-stimulated insulin secretion of isolated islets was assessed. Plasma glucose concentration of the fetal hypothyroid group during intravenous glucose tolerance test was significantly higher (p=0.003) at 5-20 min as compared to the control group, whereas plasma insulin concentration was significantly lower (p=0.012) at 5-20 min. Insulin secretion of the isolated islets stimulated with 16 mM glucose of the offspring in the fetal hypothyroid group (376.2 ± 57.1 pmol/islet/60 min) was significantly lower (p=0.02) as compared to the control group (618.1 ± 85.2). Although adult offspring born from hypothyroid mothers were euthyroid, their glucose tolerance and glucose stimulated insulin secretion of islets were altered, which may eventually contribute to the development of diabetes.
Receptor for Advanced Glycation End Products and Its Ligands: A Journey from the Complications of Diabetes to Its Pathogenesis

Abstract: Many studies have suggested that the expression of RAGE (receptor for advanced glycation end products) is upregulated in human tissues susceptible to the long‐term complications of diabetes. From the kidneys to the macrovessels of the aorta, RAGE expression is upregulated in a diverse array of cell types, from glomerular epithelial cells (podocytes) to endothelial cells, vascular smooth muscle cells, and inflammatory mononuclear phagocytes and lymphocytes. Although RAGE was first described as a receptor for advanced glycation end products (AGEs), the key finding that RAGE was also a signaling receptor for proinflammatory S100/calgranulins and amphoterin, led to the premise that even in euglycemia, ligand‐RAGE interaction propagated inflammatory mechanisms linked to chronic cellular perturbation and tissue injury. Indeed, such considerations suggested that RAGE might even participate in the pathogenesis of type 1 diabetes. Our studies have shown that pharmacological and/or genetic deletion/mutation of the receptor attenuates the development of hyperglycemia in NOD mice; in mice with myriad complications of diabetes, interruption of ligand‐RAGE interaction prevents or delays the chronic complications of the disease in both macro‐ and microvessel structures. Taken together, these findings suggest that RAGE is “at the right place and time” to contribute to the pathogenesis of diabetes and it complications. Studies are in progress to test the premise that antagonism of this interaction is a logical strategy for the prevention and treatment of diabetes.
An assessment of the impact of public health activities to reduce the prevalence of the prone sleeping position during infancy: the Tasmanian Cohort Study.

BACKGROUND An intervention to reduce the prevalence of the prone sleeping position during infancy was implemented in Tasmania particularly from 1991 onward. The purpose of this report is to assess the impact of public health activities in promoting avoidance of the prone infant sleeping position among cohort study participants. METHODS The prospective cohort study involved the one-fifth of Tasmanian live births who are assessed perinatally as being at higher risk for Sudden Infant Death Syndrome (SIDS). From 1 January 1988 until 30 April 1992, 5,403 infants participated in the hospital (4 days postnatal age) and home interviews (5 weeks postnatal age) (88% of eligible infants). After the finding that cohort infants who usually slept prone were at significantly greater risk for SIDS, additional questions on awareness and choice of infant sleep position were asked. RESULTS The proportion of infants usually sleeping prone declined from 29.9% in the cohort prior to publication of the cohort findings (1 May 1988-30 April 1991) to 5.4% in the post publication cohort (1 May 1991-30 April 1992), RR = 0.18 (0.15, 0.22). Teenage motherhood was associated with non-awareness (RR = 2.39 (1.41, 3.24)) of an association between prone position and SIDS. After adjusting for maternal age, nonawareness remained positively associated with maternal smoking, maternal education (< Year 12), and paternal unemployment, while mothers who read books to prepare for the baby and who were married were more likely to be aware. In the period after the cohort study publication, the most common reasons given for the usual prone position were that the baby preferred that position and slept better. CONCLUSION Public health activities to reduce the prevalence of the prone sleeping position have had a significant impact, with a dramatic reduction in the proportion of cohort infants usually sleeping prone. The identification of characteristics of nonaware mothers and the reasons for choosing a particular sleeping position will be used to maintain and improve health education in this area.
4-Methoxybenzamidinium bromide

The title salt, C8H11N2O+·Br−, was synthesized by the reaction between 4-methoxybenzamidine (4-amidinoanisole) and hydrobromic acid. In the cation, the amidinium group has two similar C—N bonds [1.304 (2) and 1.316 (2) Å], and its plane forms a dihedral angle of 31.08 (5)° with the benzene ring. The ions are associated in the crystal into a three-dimension hydrogen-bonded supramolecular network featuring N—H+⋯Br− interactions.
Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis

Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation.
A Study of Single Nucleotide Polymorphisms of Tumour Necrosis Factor α-1031 And Tumour Necrosis Factor β+ 252 in Chronic Rhinosinusitis

Objectives This case-controlled study aimed to identify the association of tumor necrosis factor (TNF)α-1031 and TNFβ+ 252 gene polymorphisms between chronic rhinosinusitis (CRS) and healthy controls. Another purpose of this study was to investigate the associations of these gene polymorphisms with factors related to CRS. Methods All deoxyribonucleic acid (DNA) samples were genotyped for TNFα-1031 and TNFβ+252 genes by mean of polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP). The statistical analysis were carried out using chi-square test or Fisher exact test to determine the associations of these gene polymorphisms in CRS. Multiple logistic regression was performed to evaluate the associations of these gene polymorphisms in CRS and its related risk factors. Results The genotype and allele frequencies of TNFα-1031 and TNFβ+252 gene did not show any significant associations between CRS and healthy controls. However, a significantly statistical difference of TNFα-1031 was observed in CRS participants with atopy (P-value, 0.045; odds ratio, 3.66) but not in CRS with asthma or aspirin intolerance. Conclusion Although the presence of TNFα-1031 and TNFβ+252 gene polymorphisms did not render any significant associations between CRS and healthy control, this study suggests that TNFα-1031 gene polymorphisms in CRS patients with atopy may be associated with increase susceptibility towards CRS.
Homicides with Mutilation of the Victim’s Body

Abstract: Information on homicide offenders guilty of mutilation is sparse. The current study estimates the rate of mutilation of the victim’s body in Finnish homicides and compares sociodemographic characteristics, crime history, life course development, psychopathy, and psychopathology of these and other homicide offenders. Crime reports and forensic examination reports of all offenders subjected to forensic examination and convicted for a homicide in 1995–2004 (n = 676) were retrospectively analyzed for offense and offender variables and scored with the Psychopathy Check List Revised. Thirteen homicides (2.2%) involved mutilation. Educational and mental health problems in childhood, inpatient mental health contacts, self‐destructiveness, and schizophrenia were significantly more frequent in offenders guilty of mutilation. Mutilation bore no significant association with psychopathy or substance abuse. The higher than usual prevalence of developmental difficulties and mental disorder of this subsample of offenders needs to be recognized.
Understanding the gastrointestinal manifestations of Fabry disease: promoting prompt diagnosis

Fabry disease is a rare X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement such as diarrhea, abdominal pain, early satiety and nausea. The gastrointestinal symptoms of Fabry disease are thought to be due to neuropathic and myopathic changes leading to symptoms of dysmotility that are encountered in many other disorders. The gastrointestinal symptoms can often be one of the presenting signs of the disease in childhood, but can be misdiagnosed by gastroenterologists for many years due to their nonspecific presentation. As the chief treatment for Fabry is enzyme-replacement therapy that has been shown to stabilize and possibly reverse disease course, recognition of these symptoms and early diagnosis in an attempt to prevent progression with treatment, is critical.
Widespread Occurrence of Bacterial Human Virulence Determinants in Soil and Freshwater Environments

ABSTRACT The occurrence of 22 bacterial human virulence genes (encoding toxins, adhesins, secretion systems, regulators of virulence, inflammatory mediators, and bacterial resistance) in beech wood soil, roadside soil, organic agricultural soil, and freshwater biofilm was investigated by nested PCR. The presence of clinically relevant bacterial groups known to possess virulence genes was tested by PCR of 16S and 23S rRNA genes. For each of the virulence genes detected in the environments, sequencing and NCBI BLAST analysis confirmed the identity of the PCR products. The virulence genes showed widespread environmental occurrence, as 17 different genes were observed. Sixteen genes were detected in beech wood soil, and 14 were detected in roadside and organic agricultural soils, while 11 were detected in the freshwater biofilm. All types of virulence traits were represented in all environments; however, the frequency at which they were detected was variable. A principal-component analysis suggested that several factors influenced the presence of the virulence genes; however, their distribution was most likely related to the level of contamination by polycyclic aromatic hydrocarbons and pH. The occurrence of the virulence genes in the environments generally did not appear to be the result of the presence of clinically relevant bacteria, indicating an environmental origin of the virulence genes. The widespread occurrence of the virulence traits and the high degree of sequence conservation between the environmental and clinical sequences suggest that soil and freshwater environments may constitute reservoirs of virulence determinants normally associated with human disease.
Postnatal Loss of Kindlin-2 Leads to Progressive Heart Failure

Background—The striated muscle costamere, a multiprotein complex at the boundary between the sarcomere and the sarcolemma, plays an integral role in maintaining striated muscle structure and function. Multiple costamere-associated proteins, such as integrins and integrin-interacting proteins, have been identified and shown to play an increasingly important role in the pathogenesis of human cardiomyopathy. Kindlin-2 is an adaptor protein that binds to the integrin &bgr; cytoplasmic tail to promote integrin activation. Genetic deficiency of Kindlin-2 results in embryonic lethality, and knockdown of the Kindlin-2 homolog in Caenorhabditis elegans and Danio rerio suggests that it has an essential role in integrin function and normal muscle structure and function. The precise role of Kindlin-2 in the mammalian cardiac myocyte remains to be determined. Methods and Results—The current studies were designed to investigate the role of Kindlin-2 in the mammalian heart. We generated a series of cardiac myocyte–specific Kindlin-2 knockout mice with excision of the Kindlin-2 gene in either developing or adult cardiac myocytes. We found that mice lacking Kindlin-2 in the early developing heart are embryonic lethal. We demonstrate that deletion of Kindlin-2 at late gestation or in adult cardiac myocytes resulted in heart failure and premature death, which were associated with enlargement of the heart and extensive fibrosis. In addition, integrin &bgr;1D protein expression was significantly downregulated in the adult heart. Conclusions—Kindlin-2 is required to maintain integrin &bgr;1D protein stability. Postnatal loss of Kindlin-2 from cardiac myocytes leads to progressive heart failure, showing the importance of costameric proteins like Kindlin-2 for homeostasis of normal heart function.
Significance of granulation tissue in torn supraspinatus insertions: An immunohistochemical study with antibodies against interleukin‐1β, cathepsin D, and matrix metalloprotease‐1

The pathophysiology of rotator cuff tears can be elucidated by examining the tendinous insertion of the supraspinatus musele. As seen by light microscopy, the granulation tissue around the insertion of a torn supraspinatus tendon appears to induce osteochondral destruction by means of multinucleated giant cells and chemical mediators. The purpose of this study was to examine the contribution of certain chemical mediators to osteochondral destruction using immunohistochemical analysis of interleukin‐β, cathepsin D, and matrix metalloprotease‐1. Sixteen supraspinatus insertions with portions of the greater tuberosity, including eight complete‐thickness tears and eight incomplete‐thickness tears, were obtained during surgery. Six fresh cadaveric supraspinatus tendons without grossly evident tears served as normal controls. Strong immunoreactivity was found in all 16 torn supraspinatus insertions but not in the six insertions of apparently intact tendons. Macrophages and multinucleated giant cells, which showed immunoreactivity for all three chemical mediators, were often found at the interface between the osteochondral margin of the enthesis and the granulation tissue, suggesting that they may be involved in osteochondral destruction. We therefore concluded that, in addition to repetitive subacromial impingement, this granulation tissue may contribute to the development of rotator cuff tears by weakening the insertion.
Structural Transformation and Comparative Advantage: Implications for Small Open Economies

Data from the last half-century show that revealed comparative advantage in agriculture (manufacturing) is negatively (positively) associated with the rate of decline in labour share in agriculture. Motivated by this finding, the author constructs and calibrates a simple open-economy model, where there is learning-by-doing in manufacturing and industry-supplied inputs to agricultural production. This paper focuses on the effects of comparative advantage and learning-by-doing on structural transformation and calibrate the model to the US and the UK data to estimate key parameters of the model. Quantitative experiments show that holding constant other factors a small difference in a country's comparative advantage can account for a large variation in structural transformation for open economies, which does not require nearly as much differential productivity growth as in closed-economy models.
Glycine site agonists of the N‐methyl‐d‐aspartate receptor and Parkinson's disease: A hypothesis

Limitations of current pharmacological approaches to Parkinson's disease (PD) highlight the need for the development of nondopaminergic therapeutic strategies. The potential role of glutamatergic neurotransmission modulators, including those active at the N‐methyl‐D‐aspartate receptor (NMDAR), is presently under investigation. Most literature proposes the use of NMDAR antagonists based on neurodegenerative theories of NMDAR function. Nevertheless, NMDAR antagonism has proven disappointing in clinical trials and may be associated with serious adverse events. More recent theories indicate that NMDAR target selectivity may be a cardinal prerequisite for efficacy, with present efforts being devoted primarily to development of NMDAR‐NR2B subunit antagonists. We propose a novel hypothesis according to which NMDAR stimulation, accomplished through allosteric modulation via the glycine modulatory site, may be beneficial in late‐phase PD. This hypothesis stems from: (1) meta‐analysis of randomized controlled trials performed in schizophrenia, indicating that glycine site agonists (eg, glycine, D‐serine) alleviate antipsychotic‐induced parkinsonian symptoms; (2) clinical observations indicating that NMDAR hypofunction is associated with motor disturbances; (3) results of a preliminary D‐serine trial in PD; (4) data indicating glycine efficacy in a rat tardive dyskinesia model; and (5) no evidence of excitotoxic damage following chronic high‐dose glycine nutritional supplementation. This hypothesis is discussed in the context of glycine site agonist effects on intrasynaptic NMDAR subunits and striatal synaptic plasticity. © 2013 Movement Disorder Society
Expression of the inactive C145A mutant human O6-alkylguanine-DNA alkyltransferase in E.coli increases cell killing and mutations by N-methyl-N'-nitro-N-nitrosoguanidine.

Human O6-alkylguanine-DNA alkyltransferase (AGT) counteracts the mutagenic and toxic effects of methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by removing the methyl group from O6-methylguanine lesions in DNA. The methyl group is transferred to a cysteine acceptor residue in the AGT protein, which is located at residue 145. The C145A mutant of AGT in which this cysteine is converted to an alanine residue is therefore inactive. When this C145A mutant was expressed in an Escherichia coli strain lacking endogenous alkyltransferase activity, the number of G:C-->A:T mutations actually increased and the toxicity of the MNNG treatment was enhanced. These effects were not seen when an E.coli strain also lacking nucleotide excision repair (NER) was used. The enhancement of mutagenesis and toxicity of MNNG produced by the C145A mutant AGT was not seen with another inactive mutant Y114E that contains a mutation preventing DNA binding, and the double mutant C145A/Y114E was also ineffective. These results suggest that the C145A mutant AGT binds to O6-methylguanine lesions in DNA and prevents their repair by NER. The inactive C145A mutant AGT also increased the number of A:T-->G:C transition mutations in MNNG-treated cells. These mutations are likely to arise from the minor methylation product, O4-methylthymine. However, expression of wild-type AGT also increased the incidence of these mutations. These results support the hypothesis that mammalian AGTs bind to O4-methylthymine but repair the lesion so slowly that they effectively shield it from more efficient repair by NER.