Miracle-dz/UniFAR-FTUs huggingface dataset:
The structure of flavin‐dependent tryptophan 7‐halogenase RebH

Enzyme catalyzed regio- and stereo-specific halogenations influence the biological activity of a diverse array of therapeutically important natural products, including the antibiotics vancomycin and chloramphenicol as well as the anticancer agents calicheamicin and rebeccamycin. The major class of enzymes responsible for this challenging synthetic reaction, the flavin-dependent halogenases, catalyzes the formation of carbon-halogen bonds using flavin, a halide ion (Cl{sup -}, Br{sup -} or I{sup -}), and O{sub 2}. Recent mechanistic and structural advances achieved with the model flavin-dependent tryptophan 7-halogenases PrnA and RebH have greatly enhanced the level of understanding of this unique reaction. According to these studies, the mechanism for tryptophan halogenation proceeds via FAD(C4a)-OOH activation of a chloride ion into the transient chlorinating species HOCl. The key evidence for the requirement of a transient chlorinating species is the discovery that a {approx}10-{angstrom}-long tunnel separates FAD and tryptophan in the ligand-bound form of PrnA. In a recent compelling study to elucidate the strategy by which RebH controls this highly reactive and indiscriminant oxidant, a Lys79-{var_epsilon}NH-Cl chloramine intermediate was implicated as the actual chlorinating species within RebH and a structural investigation of RebH was reported. Here we report our independent structural analysis of Lechevalieria aerocolonigenes RebH (Uni-Prot accession numbermore » Q8KHZ8, 530 amino acids) in its apo-form as well as in a complex with both tryptophan and FAD. « less
"SelfService": a theoretical protocol for autonomic distribution of services in P2P communities

In this paper, we present a theoretical protocol for autonomic distribution of services in a P2P environment, as well as the results of its simulated implementation. Our objective is to demonstrate that it is possible to obtain a distribution of the corresponding software modules that meets the requirement of the community in the absence of any centralized resource management. Instead, an acceptable balance between offer and demand is achieved via a simple "trial-and-error" mechanism, involving a simple, locally applied "reasoning" loop running independently on every peer.
Reversal of Chronic Inflammatory Pain by Acute Inhibition of Ca2+/Calmodulin-Dependent Protein Kinase II

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major protein kinase that is capable of regulating the activities of many ion channels and receptors. In the present study, the role of CaMKII in the complete Freund's adjuvant (CFA)-induced inflammatory pain was investigated. Intraplantarly injected CFA was found to induce spinal activity of CaMKII (phosphorylated CaMKII), which was blocked by KN93 [[2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine)], a CaMKII inhibitor. Pretreatment with KN93 (i.t.) dose-dependently prevented the development of CFA-induced thermal hyperalgesia and mechanical allodynia. Acute treatment with KN93 (i.t.) also dose-dependently reversed CFA-induced thermal hyperalgesia and mechanical allodynia. The action of KN93 started in 30 min and lasted for at least 2 to 4 h. KN92 (45 nmol i.t.) [2-[N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine], an inactive analog of KN93, showed no effect on CFA-induced CaMKII activation, allodynia, or hyperalgesia. Furthermore, our previous studies identified trifluoperazine, a clinically used antipsychotic drug, to be a potent CaMKII inhibitor. Inhibition of CaMKII activity by trifluoperazine was confirmed in the study. In addition, trifluoperazine (i.p.) dose-dependently reversed CFA-induced mechanical allodynia and thermal hyperalgesia. The drug was also effectively when given orally. In conclusion, our findings support a critical role of CaMKII in inflammatory pain. Blocking CaMKII or CaMKII-mediated signaling may offer a novel therapeutic target for the treatment of chronic pain.
Epigenetic Switch from Posttranscriptional to Transcriptional Silencing Is Correlated with Promoter Hypermethylation1

Changes in the distribution of methylcytosine residues along a transgene locus of tobacco (Nicotiana tabacum) in relation to the type of gene silencing were studied in parental plant leaves, calli, and regenerated plants derived thereof. Parental-silenced HeLo1 (hemizygous for locus 1) plants show posttranscriptional silencing of the residing nptII (neomycin phosphotransferase II) transgene and cytosine methylation restricted to the 3′ end and center part of the transcribed region. Here, we report that with an increasing number of cell cycles, DNA methylation changes gradually, and methylation is introduced into the promoter during cell culture and more slowly in vegetatively propagated plants. After 24 months of callus in vitro cultivation, an epigenetic variant, designated locus 1E, was obtained in which cytosine methylation of symmetrical (CG and CNG) sites was almost complete within the 5′ end of the nptII-transcribed region and the 35S promoter. Further, methylation of nonsymmetrical sites appeared de novo in the promoter, whereas this type of methylation was significantly reduced in the 3′ end of the transcribed region when compared with locus 1. The newly established epigenetic patterns were stably transmitted from calli into regenerated plants and their progeny. The protein and steady-state RNA levels remained low in locus 1E, whereas with nuclear run-on assays, no detectable amounts of primary transcripts were found along the nptII gene, indicating that the methylated promoter became inactivated. The results suggest that a switch between posttranscriptional and transcriptional gene silencing could be a mechanism leading to irrevocable shut down of gene expression within a finite number of generations.
Insertion of a Multibasic Cleavage Motif into the Hemagglutinin of a Low-Pathogenic Avian Influenza H6N1 Virus Induces a Highly Pathogenic Phenotype

ABSTRACT The highly pathogenic avian influenza (HPAI) virus phenotype is restricted to influenza A viruses of the H5 and H7 hemagglutinin (HA) subtypes. To obtain more information on the apparent subtype-specific nature of the HPAI virus phenotype, a low-pathogenic avian influenza (LPAI) H6N1 virus was generated, containing an HPAI H5 RRRKKR↓G multibasic cleavage site (MBCS) motif in HA (the downward arrow indicates the site of cleavage). This insertion converted the LPAI virus phenotype into an HPAI virus phenotype in vitro and in vivo. The H6N1 virus with an MBCS displayed in vitro characteristics similar to those of HPAI H5 viruses, such as cleavage of HA0 (the HA protein of influenza A virus initially synthesized as a single polypeptide precursor) and virus replication in the absence of exogenous trypsin. Studies of chickens confirmed the HPAI phenotype of the H6N1 virus with an MBCS, with an intravenous pathogenicity index of 1.4 and systemic virus replication upon intranasal inoculation, the hallmarks of HPAI viruses. This study provides evidence that the subtype-specific nature of the emergence of HPAI viruses is not at the molecular, structural, or functional level, since the introduction of an MBCS resulted in a fully functional virus with an HPAI virus genotype and phenotype.
Nutritional Modulation of Resistance and Resilience to Gastrointestinal Nematode Infection - A Review

Disease susceptibility is linked to nutritional status for a wide range of human and animal diseases. Nutritional status can influence both resistance (ability to resist the pathogen) and resilience (ability to tolerate or ameliorate the effects of the pathogen). This review focuses on the nutritional modulation of gastro-intestinal nematode infection in domestic ruminants, primarily sheep. It highlights the duality of the adverse consequences of infection on host nutritional status and the adverse consequences of poor host nutritional status on resistance to infection. Central to both phenomena is the complex, gut-based immune response to gastrointestinal nematode infection. The potential for strategic nutritional supplementation to enhance host resistance and resilience is reviewed together with recent findings on responses to increased ME supply, and long term effects on host immunity of short term protein supplementation.
Rivaroxaban and early periprostethic joint infection: our experience

Background and aim of the work: Periprostethic joint infection (PJI) is a severe post-operative complication after Primary Total Hip Arthroplasty (THA). According to the classification of PJI early acute PJI occurs within 4 weeks from surgery. Some authors think that Rivaroxaban is a risk factor in the incidence of early acute PJI. We analyze our experience about this item. Materials and methods: We analyze our experience from 1st January 2015 to 31th December 2016. We consider all consecutive hip arthroplasty implants in this period. Results: In the 205 patients analysed we not find early acute PJI in Rivaroxaban group nor in the others assuming another kind of thromboprophylaxis. Conclusions: In our series there is no evidence of association between Rivaroxaban and early acute PJI. This is a retrospective cohort study, so we need more studies and more robust experimental designs to confirm these results. (www.actabiomedica.it)
Dissociating perceptual and motor effects of prism adaptation in neglect

Prism adaptation reduces some symptoms of neglect; however the mechanisms underlying such changes are poorly understood. We suggest that prisms influence neglect by acting on dorsal stream circuits subserving visuomotor control, with little influence on perceptual aspects of neglect. We examined prism adaptation in three neglect patients and a group of healthy controls on line bisection and landmark tasks. Neglect patients showed a dramatic reduction in the rightward bias for line bisection, but absolutely no change in their leftward bias on the landmark task, which is a perceptual equivalent to bisection. However, in controls, prisms produced ‘neglect-like’ deficits on both the line bisection and landmark tasks. These data suggest that prisms influence visually guided actions more so than perception in neglect.
Parent–Child Interaction Therapy With a Deaf and Hard of Hearing Family

Deaf and hard of hearing (DHH) children are an exceptional needs population with unique mental health concerns requiring specialized intervention. However, psychological interventions aimed at treating these children are limited. Parent–Child Interaction Therapy (PCIT) is an empirically established therapeutic modality for the treatment of children with behavioral and emotional difficulties. This case study describes how PCIT was adapted to effectively intervene in assisting a deaf mother improve parent–child communication, bonding, and her hard-of-hearing son’s behavior. Readers will learn how PCIT was adapted and implemented with a DHH family, including the use of sign language interpreters within the model, translating PCIT behavioral coaching to American Sign Language, and an overall broadened understanding of mental health treatment with the DHH population. The effect of treatment on the child and parent who participated is also discussed.
Structure of the archaeal Cascade subunit Csa 5 Relating the small subunits of CRISPR effector complexes

Clustered regularly interspaced short palindromic repeats (CRISPRs) are a prokaryotic mechanism for preventing horizontal gene transfer (HGT) and infection by mobile genetic elements. The CRISPR array consists of identical repeats separated by short “spacers” derived from previously encountered foreign genetic elements. Linked to the CRISPR array are CRISPRassociated (cas) genes, which encode the proteins that mediate the CRISPR response to the insertion of foreign double-stranded DNA (dsDNA) or single-stranded RNA (ssRNA) into the cell. 10 The response can be divided into three stages: adaptation, the integration of new spacers into the CRISPR array; expression, the transcription of the array and processing of the transcript to short, mature CRISPR RNAs (crRNA); interference, the recognition and degradation of foreign dsDNA or ssRNA. cas genes are arranged in loci, which can be classified into one of three main systems (types I, II and III) based on the identity and order of genes in the locus. The CRISPR/Cas systems can be further subdivided into a total of 10 subtypes (Fig. S1), all of The cascade complex for cRIspR-mediated antiviral immunity uses cRIspR RNA (crRNA) to target invading DNA species from mobile elements such as viruses, leading to their destruction. The core of the cascade effector complex consists of the cas5 and cas7 subunits, which are widely conserved in prokaryotes. cas7 binds crRNA and forms the helical backbone of cascade. Many archaea encode a version of the cascade complex (denoted Type I-A) that includes a csa5 (or small) subunit, which interacts weakly with the core proteins. here, we report the crystal structure of the csa5 protein from Sulfolobus solfataricus. csa5 comprises a conserved α-helical domain with a small insertion consisting of a weakly conserved β-strand domain. In the crystal, the csa5 monomers have multimerized into infinite helical threads. At each interface is a strictly conserved intersubunit salt bridge, deletion of which disrupts multimerization. structural analysis indicates a shared evolutionary history among the small subunits of the cRIspR effector complexes. The same α-helical domain is found in the c-terminal domain of cse2 (from Type I-e cascade), while the N-terminal domain of cse2 is found in cmr5 of the cMR (Type III-B) effector complex. As cmr5 shares no match with csa5, two possibilities present themselves: selective domain loss from an ancestral cse2 to create two new subfamilies or domain fusion of two separate families to create a new cse2 family. A definitive answer awaits structural studies of further small subunits from other cRIspR effector complexes. Structure of the archaeal Cascade subunit Csa5 Relating the small subunits of CRISPR effector complexes
A Digitally Controlled 4-kW Single-Phase Bridgeless PFC Circuit for Air Conditioner Motor Drive Applications

Today's air conditioner applications demand a one-chip solution that simultaneously controls power-factor-correction (PFC) frond-end and two permanent magnetic (PM) motor sensorless drives, by using a single digital control IC. However, digital control has fundamental limitations that make most of conventional digital PFC control approaches unpractical. Implementation and integration of PFC control into digital ICs have been a quite challenge. International Rectifier recently introduced a new digital control IC that is based on the hardware computation engine called motion control engine (MCE). Unique advanced digital PFC control algorithms have been developed, and it becomes practical to integrate digital PFC with 2 PM motor sensorless control into a single digital IC. Based the new control IC, a 4-kW air conditioner outdoor unit which uses a bridgeless PFC frond-end has been designed, built and tested. This paper analyzes the fundamental limitations of conventional digital PFC control, presents the design and implementation of the 4-kW unit, and experimentally demonstrates the superior performance of the proposed digital PFC control
Determination of polychlorinated biphenyl and polycyclic aromatic hydrocarbon elimination rates in adult green and leopard frogs

The purpose of the present study was to quantify elimination kinetics of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in adult green frogs (Rana clamitans) and leopard frogs (Rana pipiens). Three experiments were conducted: PCB elimination rate constants were determined for both frog species, and PAH elimination rate constants were determined for leopard frogs only. In green frogs, significant PCB elimination rate constants ranged from 0.013 to 0.04 d−1 (time for frogs to achieve 90% steady state with water [t90] = 57.8‐178.2 d). In leopard frogs, significant PCB elimination rate constants ranged from 0.004 to 0.047 d−1 (t90 = 48.8‐657.9 d). Polycyclic aromatic hydrocarbon elimination in leopard frogs was faster than PCB elimination in either frog species: Significant PAH rate constants ranged from 0.069 to 0.188 d−1 (t90 = 12.2‐33.5 d). In both species, and for both PCBs and PAHs, a significant inverse relationship was found between the chemical elimination rate constant and Kow. These results show that adult anurans have relatively low elimination rates of PCBs but exhibit a small capacity for metabolic biotransformation of PAHs that is comparable to that of invertebrates but lower than that of fish. These findings suggest that adult amphibians have the potential to be used as biomonitors for persistent organic chemicals.
Level of Macrophage uPA Expression Is an Important Determinant of Atherosclerotic Lesion Growth in Apoe−/− Mice

Objective—Enhanced plasminogen activation, mediated by overexpression of urokinase-type plasminogen activator (uPA), accelerates atherosclerosis in apolipoprotein E–null mice. However, the mechanisms through which uPA acts remain unclear. In addition, although elevated uPA expression can accelerate murine atherosclerosis, there is not yet any evidence that decreased uPA expression would retard atherosclerosis. Methods and Results—We used a bone marrow transplant (BMT) approach and apolipoprotein E–deficient (Apoe−/−) mice to investigate cellular mechanisms of uPA-accelerated atherosclerosis, aortic dilation, and sudden death. We also used BMT to determine whether postnatal loss of uPA expression in macrophages retards atherosclerosis. BMT from uPA-overexpressing mice yielded recipients with macrophage-specific uPA overexpression; whereas BMT from uPA knockout mice yielded recipients with macrophage-specific loss of uPA expression. Recipients of uPA-overexpressing BM acquired all the vascular phenotypes (accelerated atherosclerosis, aortic medial destruction and dilation, severe coronary stenoses) as well as the sudden death phenotype of uPA-overexpressing mice. Moreover, fat-fed 37-week-old recipients of uPA-null BM had significantly less atherosclerosis than recipients of uPA wild-type marrow (40% less aortic surface lesion area; P=0.03). Conclusions—The level of uPA expression by macrophages—over a broad range—is an important determinant of atherosclerotic lesion growth in Apoe−/− mice.
Culture And Student Samples As Moderators Of Continued IT Usage: A Meta-Analysis Of IS Continuance Literature

The benefits from ICT investments materialize through sustained usage rather than initial acceptance. Hence, the amount of research on continued IT usage (IS continuance) employing the ExpectationConfirmation Model (ECM) has been increasing steadily in recent years. In this body of literature, empirical results regarding the correlations between the key constructs of ECM have not been entirely consistent. Thus, we conduct a meta-analysis of prior IS continuance literature to examine whether the flux in the results can be explained by the presence of moderating effects. First, we investigate whether the cultural context of the empirical study or the use of student samples has influenced the results. Second, we examine whether including perceived ease of use in the ECM has received consistent empirical support. The results demonstrate that both cultural context and student samples potentially act as moderators, and thus have caused the flux in the empirical results. Furthermore, the results show that perceived ease of use is a viable extension to ECM.
Improvement of psoriasis after antibiotic therapy with cefuroxime axetil

References 1 Asero R, Cugno M, Tedeschi A. Chronic idiopathic urticaria: what is the meaning of skin reactivity to autologous serum? J Eur Acad Dermatol Venereol 2008; 22 : 135–136. 2 Guttman-Yassky E, Bergman R, Pollack S, Shahar E. Chronic idiopathic urticaria: what is the meaning of skin reactivity to autologous serum? J Eur Acad Dermatol Venereol 2008; 22 : 136. 3 Taskapan O, Kutlu A, Karabudak O. Evaluation of autologous serum skin test results in patients with chronic idiopathic urticaria, allergic/non-allergic asthma or rhinitis and healthy people. Clin Exp Dermatol 2008; 33 : 754–758. 4 Mari A. Allergy-like asthma and rhinitis – a cross sectional survey of a respiratory cohort and a diagnostic approach using the autologous serum skin test. Int Arch Allergy Immunol 2004; 133 : 29–39. 5 Tedeschi A, Comi AL, Lorini M et al . Autologous serum skin test reactivity in patients with non-allergic asthma. Clin Exp Allergy 2005; 35 : 849–853. 6 Sabroe RA, Grattan CEH, Francis DM et al . The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. Br J Dermatol 1999; 140 : 446–452. 7 Asero R, Tedeschi A, Lorini M et al . Sera from patients with multiple drug allergy syndrome contain circulating histamine-releasing factors. Int Arch Allergy Immunol 2003; 131 : 195–200. 8 Sabroe RA, Fiebiger E, Francis DM et al . Classification of anti-Fc ε RI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity. J Allergy Clin Immunol 2002; 110 : 492–499. 9 Guttman-Yassky E, Bergman R, Maor C et al . The autologous serum skin test in a cohort of chronic idiopathic urticaria patients compared to respiratory allergy patients and healthy individuals. J Eur Acad Dermatol Venereol 2007; 21 : 35–39.
Shade-Matching Performance Using a New Light-Correcting Device.

PURPOSE To evaluate the shade-matching performance of dental students when using a new light-correcting device with polarization filter. MATERIALS AND METHODS A total of 21 observers assessed the shade of the upper frontal teeth in one patient under three lighting conditions: daylight (A), daylight and a light-correcting device (Smile Lite, Switzerland) (B), daylight and a light-correcting device with a polarization filter attached (C) by using two shade guides: VITA Classical and 3D Master. Matching scores were calculated as a sum of the color differences between the reference shades and the selected shades (ΔEab *). Data were analyzed using analysis of variance (ANOVA) test (α = 0.05). RESULTS A significant difference was found between the shade-matching scores under the three lighting conditions (p < 0.001). However, pairwise comparisons showed that between A (ΔEab *A = 1,873.6) and C (ΔEab *C = 2,019.1), there was no significant difference (p > 0.05). The best matching scores were calculated for B (ΔEab *B = 1,652.5). Significant differences were found in respect to the observer's gender (p < 0.05) and color competency (p < 0.05), as well as with the shade guide used (p < 0.05). CONCLUSIONS Dental students' shade-matching ability was better when the light-correcting device was used, but the addition of the filter to it did not prove beneficial. The shade guides used, the observer's gender, and color competency influenced the shade matching. CLINICAL SIGNIFICANCE The light-correcting device influenced the shade-matching performance; however, the attached polarization filter did not improve the results of the shade matching.