Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the nisin gene cluster nisABTCIPR of Lactococcus lactis. Requirement of expression of the nisA and nisI genes for development of immunity.

The nisin gene cluster nisABTCIPR of Lactococcus lactis, located on a 10-kbp DNA fragment of the nisin-sucrose transposon Tn5276, was characterized. This fragment was previously shown to direct nisin-A biosynthesis and to contain the nisP and nisR genes, encoding a nisin leader peptidase and a positive regulator, respectively [van der Meer, J. R. , Polman, J., Beerthuyzen, M. M. , Siezen, R. J., Kuipers, O. P. & de Vos, W. M. (1993) J. Bacteriol. 175, 2578-2588]. Further sequence analysis revealed the presence of four open-reading frames, nisB, nisT, nisC and nisI, downstream of the structural gene nisA. The nisT, nisC and nisI genes were subcloned and expressed individually in Escherichia coli, using the T7-RNA-polymerase system. This resulted in the production of radiolabelled proteins with sizes of 45 kDa (NisC) and 32 kDa (NisI). The nisT gene product was not detected, possibly because of protein instability. The deduced amino acid sequence of NisI contained a consensus lipoprotein signal sequence, suggesting that this protein is a lipid-modified extracellular membrane-anchored protein. Expression of nisI in L. lactis provided the cells with a significant level of protection against exogenously added nisin, indicating that NisI plays a role in the immunity mechanism. In EDTA-treated E. coli cells, expression of nisI conferred up to a 170-fold increase in immunity against nisin A compared to controls. Moreover, a lactococcal strain deficient in nisin-A production, designated NZ9800, was created by gene replacement of nisA by a truncated nisA gene and was 10-fold less resistant to nisin A than the wild-type strain. A wild-type immunity level to nisin and production of nisin was obtained in strain NZ9800 harboring complementing nisA and nisZ plasmids. Transcription analyses of several L. lactis strains indicated that an expression product of the nisA gene, together with NisR, is required for the activation of nisA transcription.
Toward a better understanding of implementation performance in the EU multilevel system

ABSTRACT The results of this collection allow for preliminary conclusions about the nuanced interplay between Europeanization and domestication forces in European Union (EU) implementation, which await testing in different contexts. Some policies lend themselves more to a strategy allowing for extensive domestication than others; but to be effective, decentralized implementing actors need both power and capabilities. Europeanization dynamics strongly influence the direction of domestication of EU policy, but if EU requirements are incompatible with national political preferences domestication trumps Europeanization. Domestication equally prevails if the relationship between EU and national policy is ambiguous and frontline implementers have high discretion. The trend toward the Europeanization of direct EU enforcement challenges its legitimacy. This has implications for EU researchers and practitioners, and suggests methodological challenges and future research trajectories for a performance perspective on EU implementation. More comparative research is needed about the trade-offs between conformance, diversity, and performance in EU multilevel governance.
Cutaneous Low-Dose Radiation Increases Tissue Vascularity through Upregulation of Angiogenic and Vasculogenic Pathways

Background/Aims: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. Methods: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. Results: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. Conclusion: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally.
TNF Signaling through RIP1 Kinase Enhances SN38-Induced Death in Colon Adenocarcinoma

Elucidation of TNF-directed mechanisms for cell death induction and maintenance of tumor growth has revealed a role for receptor-interacting protein kinases 1 and 3 (RIPK1/RIP1 and RIPK3/RIP3), components of the necrosome complex, as determinants of cell fate. Here, the participation of TNF signaling was analyzed with regard to the cytotoxic action of different DNA-damaging agents in a panel of colon cancer cells. While most of these cell lines were insensitive to TNF, combination with these drugs increased sensitivity by inducing cell death and DNA damage, especially in the case of the topoisomerase inhibitor SN38. Changes in levels of RIP1 and RIP3 occurred following monotherapy with SN38 or in combination with TNF. Downregulation of RIP1 resulted in increased resistance to SN38, implying a requirement for RIP1 in mediating cytotoxicity through the TNF/TNFR signaling pathway. Downregulation of RIP1 in a xenograft model impaired tumor growth inhibition from SN38 treatment, suggesting the potential of RIP1 to determine the clinical outcome of irinotecan treatment. These results indicate that TNF plays a key role in determining the cytotoxic effectiveness of SN38 in colorectal cancer and suggests a re-evaluation of TNF-based interventions to enhance therapeutic efficacy. Implications: The capacity of RIP1 to influence drug sensitivity suggests RIP1 may have biomarker potential. Mol Cancer Res; 15(4); 395–404. ©2017 AACR.
Surface Composition as Bridging

The development of explicit theories of dynamic context change has led to a fundamentally new perspective on the interpretation of discourse. In this paper I show that this development also opens up the possibility of approaching subclausal composition along similar lines. More specifically, I propose a dynamic Bridging Theory, where type-driven rules apply directly to overt surface structures and proceed by building anaphoric bridges. I then present three arguments that this dynamic approach is more faithful to natural language semantics than static Montagovian theories. First, the Bridging Theory explains how dynamic phenomena, such as temporal anaphora, generalize across different levels - from discourse all the way down to the lexicon - in typologically distant languages. Second, it explains the shift from defeasible defaults in discourse to structural determinism lower down, in terms of the type diversity needed to support type-driven bridging. Deterministic type-driven bridging also makes detailed predictions about the exact impact of the structure on top-level anaphora, in various domains, and other presuppositional phenomena that it mediates. And last but not least, the Bridging Theory combines a strong claim that semantics is universal - bridgeable basic meanings are typically universal and type-driven bridges, all universal - with the ideal of strict surface composition.
IL-10-Producing Lymphocytes in Inflammatory Disease

IL-10 is an anti-inflammatory cytokine that plays a significant role in controlling inflammation and modulating adaptive immune responses that cause tissue damage. IL-10-producing lymphocytes contribute to the delicate balance between inflammation and immunoregulation, and are thus regarded as a kind of “regulatory cells. ” Dysregulation of these cells is linked with susceptibility to numerous inflammatory diseases. In this review, we summarized what is known about the regulatory effects of IL-10 produced by lymphocytes, including T cells, B cells and natural killer cells, in inflammatory diseases. We hope to augment immune responses or prevent immunopathology through making some small changes in the levels of IL-10 produced by lymphocytes, or in the cellular location where it is produced.
Osteoporosis‐Related Kyphosis and Impairments in Pulmonary Function: A Systematic Review

We conducted a systematic review to examine the relationship between osteoporotic vertebral fractures, kyphosis, and pulmonary function. Findings suggest modest but predictable declines in vital capacity related to the degree of kyphosis. However, there were only four studies, and all had significant methodologic limitations. Further high‐quality research is needed.
Intraganglionic injection of a nitric oxide donator induces afferent mechanical sensitization that is attenuated by palmitoylethanolamide

Aim The aim of this article is to investigate whether the nitric oxide (NO) donator diethylenetriamine/nitric oxide (DETA/NO) affects trigeminal sensory processing through the trigeminal ganglion in part by activating trigeminal satellite glial cells (SGCs) and whether this effect is attenuated by the anti-inflammatory compound palmitoylethanolamide (PEA). Methods DETA/NO was administered to isolated rat trigeminal SGCs in vitro, and injected into the rat trigeminal ganglion in vivo, in the presence or absence of PEA. Results Administration of DETA/NO (1000 µM) increased the release of prostaglandin E2 by SGCs. PEA (1 and 10 µM) significantly attenuated prostaglandin E2 release. Two intraganglionic injections of DETA/NO (10 mM, 3 µl) or prostaglandin E2 at a 30-minute interval did not evoke discharge in trigeminal ganglion neurons that innervate the rat jaw-closer muscles, but did reduce the mechanical activation threshold of their peripheral endings by 30%–50%. Intravenous administration of PEA (1 mg/kg) or ketorolac (0.5 mg/kg) prevented DETA/NO-induced afferent mechanical sensitization. Conclusions Elevation of NO in the trigeminal ganglion results in the sensitization of the peripheral endings of masticatory muscle nociceptors to mechanical stimulation through a mechanism that involves prostaglandin E2 release from SGCs. Attenuation of this sensitization by PEA suggests a possible option for acute management of craniofacial pain and headache.
Environment, Equity, and Economic Development Goals: Understanding Differences in Local Economic Development Strategies

What role do local governments play in promoting sustainable economic development? This study uses a 2014 national survey to analyze the relationship between local environment and social equity motivations and the kinds of economic development strategies local governments pursue (business incentives or community economic development policies). Municipalities that pay more attention to environmental sustainability and social equity use higher levels of community economic development tools and lower levels of business incentives. These places are also more likely to have written economic development plans and involve more participants in the economic development process. In contrast, communities that use higher levels of business incentives have lower income and are more dependent on manufacturing employment. Other capacity measures do not differentiate types of economic development strategies used. This suggests that sustainable economic development strategies can be pursued by a broad array of communities, especially if the motivations driving their economic development policy include environment and equity goals.
Continuous Exposure of Mice to Superantigenic Toxins Induces a High-Level Protracted Expansion and an Immunological Memory in the Toxin-Reactive CD4+ T Cells

We analyzed the responses of several T cell fractions reactive with superantigenic toxins (SAGTs), staphylococcal enterotoxin A (SEA), or Yersinia pseudotuberculosis-derived mitogen (YPM) in mice implanted with mini-osmotic pumps filled with SEA or YPM. In mice implanted with the SEA pump, SEA-reactive Vβ3+CD4+ T cells exhibited a high-level protracted expansion for 30 days, and SEA-reactive Vβ11+CD4+ T cells exhibited a low-level protracted expansion. SEA-reactive CD8+ counterparts exhibited only a transient expansion. A similar difference in T cell expansion was also observed in YPM-reactive T cell fractions in mice implanted with the YPM pump. Vβ3+CD4+ and Vβ11+CD4+ T cells from mice implanted with the SEA pump exhibited cell divisions upon in vitro restimulation with SEA and expressed surface phenotypes as memory T cells. CD4+ T cells from mice implanted with the SEA pump exhibited high IL-4 production upon in vitro restimulation with SEA, which was due to the enhanced capacity of the SEA-reactive CD4+ T cells to produce IL-4. The findings in the present study indicate that, in mice implanted with a specific SAGT, the level of expansion of the SAGT-reactive CD4+ T cell fractions varies widely depending on the TCR Vβ elements expressed and that the reactive CD4+ T cells acquire a capacity to raise a memory response. CD8+ T cells are low responders to SAGTs.
Reforms and Regional Inequalities in India

The regional inequalities continue to attract the attention of researchers and the policy makers. The heterogeneous nature of the Indian economy has resulted in wide inequalities despite positive interventions by the governments at various levels. There is also an explicit fear that the liberalisation policies might have resulted in further divergences. The present study aims at analysing the trends in inequalities in the levels of income and growth of the major seventeen state economies of India for the period 1980-81 through 2000-01. An adjusted series of NSDP data was constructed by adopting a specific methodology for the purpose of inter-temporal comparison. The analysis reveals divergence of state incomes, especially after the initiation of economic reforms since 1990-91. The income inequalities at aggregate as well as per capita level have increased as is evident in the increasing values of the co-efficient of variation (CVs). Different measures of Convergence/Divergence have also been estimated. The study makes many policy recommendations for realising better regional balance in the economy.
Alimentary Canal of the Blow Fly Chrysomya megacephala (F.) (Diptera: Calliphoridae): An Emphasis on Dissection and Morphometry

ABSTRACT: The alimentary canal is a major organ system that is often involved in the transmission of pathogens to humans from insects that serve as vectors of disease. In this study, we investigated the alimentary canal of the blow fly, Chrysomya megacephala (F.) (Diptera: Calliphoridae), highlighting the description for dissection and morphometric analysis of each organ. Dissection was performed in a phosphate buffer solution (pH=7.4) on 3rd instar larvae (three to four days old) and on both male and female adults (seven days old). Larval dissection was accomplished using two fine forceps to open the specimens from the posterior end and proceed anteriorly toward the cephalic segment. Meticulous dissection of the anterior end was vital for observation of the delicate salivary ducts, crop duct, and esophagus. Overall length of the 3rd instar alimentary canal measured 89.15 mm (range 81.40–99.70 mm). The midgut comprised the longest portion, measuring 46.35 mm (range 40.00–52.00 mm; n = 30) of the entire canal. Adult dissection was also performed from abdomen to head. Morphometric analyses revealed that the alimentary canal of males and females were relatively similar. No statistical differences were found between the entire length of the alimentary canal from mouth to anus (excluding all branches of the salivary glands, crop, and Malpighian tubules) of males and females. The alimentary canals of males measured 36.23 mm (range 32.60–41.20 mm) in length; whereas, those of females measured 37.23 mm (range 32.70–42.15 mm). Two-thirds of the entire canal length was comprised of midgut in each sex.
Legalized physician-assisted suicide in Oregon--the second year.

BACKGROUND AND METHODS In 1997, Oregon legalized physician-assisted suicide. We have previously reported data on terminally ill Oregon residents who received prescriptions for lethal medications under the Oregon Death with Dignity Act and who died in 1998. We now report similar data for 1999, obtained from physicians' reports, death certificates, and interviews with physicians. We also report data from interviews with family members. RESULTS Information on 33 persons who received prescriptions for lethal medications in 1999 was reported to the Oregon Health Division; 26 died after taking the lethal medications, 5 died from their underlying illnesses, and 2 were alive as of January 1, 2000. One additional patient, who received a prescription in 1998, died after taking the medication in 1999. Thus, 27 patients died after ingesting lethal medications in 1999 (9 per 10,000 deaths in Oregon), as compared with 16 patients in 1998 (6 per 10,000). The median age of the 27 patients who died in 1999 after taking lethal medications was 71 years. The most frequent underlying illnesses were cancer (in 17 patients), amyotrophic lateral sclerosis (in 4), and chronic obstructive pulmonary disease (in 4). All 27 patients had health insurance, 21 were receiving hospice care, and 13 were college graduates. According to both physicians and family members, patients requested assistance with suicide for several reasons, including loss of autonomy, loss of control of bodily functions, an inability to participate in activities that make life enjoyable, and a determination to control the manner of death. CONCLUSIONS In the second as compared with the first year of legalized physician-assisted suicide in Oregon, the number of patients who died after ingesting lethal medications increased, but it remained small in relation to the total number of persons in Oregon who died. Patients who request assistance with suicide appear to be motivated by several factors, including loss of autonomy and a determination to control the way in which they die.
Mitiglinide: a rapid- and short-acting non-sulfonylurea insulinotropic agent for the treatment of type 2 diabetic patients

This review article deals with mitiglinide, a rapid-acting non-sulfonylurea insulinotropic agent for the treatment of type 2 diabetic patients. Attention is drawn to the background history of mitiglinide, its chemistry, its determination in plasma, its metabolic pathway, preclinical investigations conducted – either in vitro on the uptake of mitiglinide by pancreatic islets, the effects of mitiglinide on ionic channels, its insulinotropic action and its effect on glucose metabolism in hepatocytes and its cardiovascular effects, or in vivo in animals – as well as to clinical investigations with mitiglinide.
Lung function changes in wildland firefighters working at prescribed burns

Context: Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. Objectives: We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season. Materials and Methods: We measured forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow from 25% to 75% of FVC (FEF25–75), and peak expiratory flow (PEF) of wildland firefighters before and after their workshifts. In all, 501 pre-shift and 488 post-shift measurements were collected over 22 prescribed burn days and 43 non-burn days from 24 non-smoking wildland firefighters during the dormant winter burn seasons of 2003 and 2004. We compared changes in the spirometry measures across the workshift on burn days to those observed on non-burn days. We also assessed the effect of cumulative exposure during the burn season on the spirometry measures. Results: There were no significant differences in the across workshift changes on burn days compared to those on non-burn days for all the spirometry measures. However, for a given point in time during the season, each additional day of exposure was estimated to be associated with declines of 24 ml in pre-shift FVC and 24 ml in pre-shift FEV1 (p <0.01). Discussion and Conclusion: Cumulative exposure to woodsmoke was associated with slight decrements in lung function among the wildland firefighters.
Paneth cell alpha-defensins from rhesus macaque small intestine.

Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity. To investigate the role of alpha-defensins in enteric host defenses in nonhuman primates, alpha-defensin cDNAs were isolated, alpha-defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured. Six rhesus enteric alpha-defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library; the deduced RED peptides exhibited extensive diversity relative to the primary structures of rhesus myeloid alpha-defensins. RED-4 was purified from monkey jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified two N termini, RTCYCRTGR. and TCYCRTGRC. ; these corresponded to alternative N termini for the RED-4 molecules, as deduced from their molecular masses and RED cDNAs. In situ hybridization experiments localized RED mRNAs exclusively to small intestinal Paneth cells. Recombinant RED-1 to RED-4 were purified to homogeneity and shown to be microbicidal in the low micromolar range (</=10 micro g/ml) against gram-positive and gram-negative bacteria, with individual peptides exhibiting variable target cell specificities. Thus, compared to myeloid alpha-defensins from rhesus macaques, enteric alpha-defensin peptides are highly variable in both primary structure and activity. These studies should facilitate further analyses of the role of alpha-defensins in primate enteric immunity.
Fragile X carrier screening in Korean women of reproductive age

Objective To estimate the distribution of the FMR1 alleles and the prevalence of the premutaion (PM) and full mutation (FM) of the FMR1 gene in Korean women of reproductive age. Methods Using polymerase chain reaction and Southern blot, 5829 women of reproductive age were screened (low-risk group n = 5470 and high-risk group n = 359) and 11 prenatal diagnoses were completed between September 2003 and December 2011. Results Of the 5829 women screened, normal FMR1 alleles (11,607) had a bimodal distribution with most alleles having 29 (37.87%) and 30 (31.87%) CGG repeats. Of the 5470 women in the low-risk group, 7 PM were identified, giving a PM carrier frequency of 1:781; none of the women had Fragile X syndrome. We also identified 38 intermediate alleles, with a reported incidence of 1:143. Of the 11 prenatal diagnoses, five were normal, five had a premutation, and one had a full mutation allele. Conclusions The carrier frequency is 1/781 (0.13%) in Korean women of reproductive age. This is lower than among Caucasians, but relatively higher than in other Asian populations. Although there may be a founder effect, these results might be valuable in understanding Fragile X syndrome in Koreans and Asians as a whole.