Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement of secretagogue-induced adrenocorticotropic hormone release from cultured sheep anterior pituitary cells by recombinant ovine interleukin 1.

OBJECTIVE To determine whether recombinant ovine interleukin (oIL)-1 or oIL-2 alters basal or hypothalamic peptide-induced secretion of ACTH from cultured sheep pituitary cells. ANIMALS The pituitary gland was collected from castrated male sheep ranging from 0.5 to 1 year old. PROCEDURE Cells were cultured for 3 to 5 days, then were treated with oIL for variable periods. Cells were washed and treated with the hypothalamic peptides corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP) or both. Medium bathing the cells was collected and assayed for ACTH concentration. RESULTS Ovine IL-1 alpha and oIL-1 beta, but not oIL-2, increased the amount of ACTH released in response to CRH, AVP, and CRH and AVP combined. Both oIL were effective after 3, but not 18 or 24 hours of exposure. Treatment with oIL-1 did not affect basal release of ACTH. Exposure of cells to phorbol 12-myristate 13-acetate or calphostin C before treatment with oIL-1 beta inhibited the ability of the cytokine to augment ACTH release, suggesting a role for protein kinase C in the process. CONCLUSIONS Local concentration of oIL-1 in the sheep pituitary gland may have an important role in determining secretion of ACTH in response to CRH or AVP or both from the hypothalamus. CLINICAL RELEVANCE The hypothalamic-pituitary-adrenocortical axis may be activated after immune challenge. The cytokine oIL-1 has been implicated as an important mediator in this process. The pituitary gland may be an important target for this effect.
Predictors of sudden onset of sleep in Parkinson's disease

With respect to the ongoing discussion of “sleep attacks” in Parkinson's disease (PD), we sought to estimate the prevalence of sudden onset of sleep (SOS) with and without preceding sleepiness in PD, to identify associated factors, and to define the role of antiparkinsonian medication in SOS. We sent a questionnaire about SOS, sleep behaviour, and medication to 12,000 PD patients. The response rate was 63%, from which 6,620 complete data sets could be analysed. A total of 42.9% of our population reported SOS, 10% of whom never experienced sleepiness before the appearance of SOS (4.3% of all), and we identified the administration of all dopaminergic drugs as a risk factor for SOS. However, SOS occurred earlier after introduction of nonergoline dopamine agonists (DA) and was more strongly associated with nonergoline DA in younger patients (below 70 years) with a shorter disease duration (up to 7 years) but, actually, medication was less efficient in predicting SOS than most other factors considered such as higher age, male sex, longer disease duration, and the report of sleep disturbances. This survey strongly suggests that SOS is a multifactorial phenomenon. Some subgroups are at particular risk of experiencing SOS under nonergoline DA, especially at the beginning of this therapy. Our results support the current notion that SOS, in part, can be attributed to PD‐specific pathology because disease duration and subjective disease severity have been shown to be predictors of SOS. We recommend the development of a standardised question to recognise SOS and to facilitate the comparison of prevalence estimates. © 2004 Movement Disorder Society
A laboratory assessment of coronal bacterial leakage in root canals filled with new and conventional sealers.

AIM To evaluate the resistance to ex vivo bacterial leakage over a 40-day period of root canal fillings with five new root canal sealers: RC Sealer, Epiphany, EndoREZ, GuttaFlow and Acroseal, compared with Apexit, AH Plus and RoekoSeal. METHODOLOGY One hundred and forty-four single rooted human teeth were divided randomly into eight test (n = 15) and two control groups (n = 12). The root canals were filled using a single cone technique with gutta-percha except in the Epiphany and EndoREZ groups. These were filled with Resilon and resin-coated gutta-percha, respectively. The gutta-percha surface of the GuttaFlow group was coated with an experimental primer prior to filling. Positive controls were filled with gutta-percha without sealer and tested with bacteria, whereas negative controls were sealed with wax to test the seal between the chambers. Filled roots were incorporated in a split chamber model system using Streptococcus mutans as a microbial marker. Leakage was assessed for turbidity of the broth in the lower chamber every day for 40 days. Survival analysis was performed using the Kaplan-Meier product limit method and event times were compared using the Log-rank test (alpha = 0.05). RESULTS Epiphany, GuttaFlow with test primer and Apexit prevented leakage significantly better than AH Plus, RC Sealer, RoekoSeal, EndoREZ and Acroseal (P < 0.05). None of the specimens in the AH Plus, RC Sealer, RoekoSeal and EndoREZ groups resisted bacterial penetration for 40 days. CONCLUSION The new sealers, Epiphany and GuttaFlow with primer, along with Apexit, showed better resistance to bacterial penetration than the other new or traditional sealers tested.
Protein misfolding inside cells: The case of huntingtin and Huntington's disease

Huntington's disease is one of the several neurodegenerative diseases caused by dominant mutations that expand the number of glutamine codons within an existing poly‐glutamine (polyQ) repeat sequence of a gene. An expanded polyQ sequence in the huntingtin gene is known to cause the huntingtin protein to aggregate and form intracellular inclusions as disease progresses. However, the role that polyQ‐induced aggregation plays in disease is yet to be fully determined. This review focuses on key questions remaining for how the expanded polyQ sequences affect the aggregation properties of the huntingtin protein and the corresponding effects on cellular machinery. The scope includes the technical challenges that remain for rigorously assessing the effects of aggregation on the cellular machinery. © 2008 IUBMB IUBMB Life, 60(11): 724–728, 2008
Lithium-Ion Capacitor - Optimization of Thermal Management from Cell to Module Level

This paper represents the thermal behavior of a lithium-ion capacitor. In this study, an extended parameter analysis has been realized for observing the thermal behavior when applying dedicated load profiles. Based on the performed analysis, an electro-thermal model and a 3D thermal model have been developed for future optimization of a thermal strategy. The model has been implemented using COMSOL Multiphysics and parameters were obtained from experiments on a 2300-F lithium-ion capacitor cell from JM energy. The accuracy of this model is tested under different operating conditions and simulations are in agreement with experimental results. The developed models are in good agreement with the experimental results, which indicates that the models can be used for the design and optimization of the thermal management.
Adoptive Transfer of Primed CD4+ T-Lymphocytes Induces Pattern of Chronic Allograft Nephropathy in a Nude Rat Model

Background. Chronic allograft nephropathy (CAN) remains the most common cause of late graft loss in renal transplantation. Presensitized patients have a specifically increased risk to lose their graft. To analyze the immunological factors involved, a new experimental rat model was created with nude athymic LEW.RNU rats as recipients of F344 renal allografts. Methods. Adoptive transfer of CD4+ T-lymphocytes (2×, 3.5×, or 5×107 cells) primed against donor skin grafts was performed one week after transplantation. The animals were monitored for renal function, graft infiltrating cells, and the development of donor specific alloantibodies for 20 weeks or until graft loss. Results. Survival of the animals was dose dependent; rats suffered from renal failure with severe albuminuria and developed various lesions typical for CAN including interstitial fibrosis and tubular atrophy. The cell infiltrate in the graft increased with the amount of CD4+ T-cells transferred and consists predominantly of CD4+ T-cells and macrophages/monocytes. More than half of the grafts showed histological signs of glomerulopathy consistent with CAN. 9/12 rats with CAN had antibodies against the donor major histocompatibility complex (MHC)-I and in all rats donor specific anti-glomerular basement membrane (GBM) antibodies were detected. Conclusion. Adoptive transfer of primed CD4+ T-cells results in a severe infiltrate of CD4+ cells in the graft and production of anti-MHC and GBM antibodies in this nude rat model. Histological changes are consistent with CAN with frequent glomerular changes. In conclusion, the induction of donor specific alloantibodies by primed CD4+ T-lymphocytes may play an important role in the pathogenesis of CAN.
Placental 11β‐hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure

OBJECTIVE Placental 11β‐hydroxysteroid dehydrogenase (11β‐HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11β‐HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas.
Phenotypes and Genotypes of Erythromycin-ResistantStreptococcus pyogenes Strains in Italy and Heterogeneity of Inducibly Resistant Strains

ABSTRACT A total of 387 clinical strains of erythromycin-resistant (MIC, ≥1 μg/ml) Streptococcus pyogenes, all isolated in Italian laboratories from 1995 to 1998, were examined. By the erythromycin-clindamycin double-disk test, 203 (52.5%) strains were assigned to the recently described M phenotype, 120 (31.0%) were assigned to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS) phenotype, and 64 (16.5%) were assigned to the constitutive MLS resistance (cMLS) phenotype. The inducible character of the resistance of the iMLS strains was confirmed by comparing the clindamycin MICs determined under normal testing conditions and those determined after induction by pregrowth in 0.05 μg of erythromycin per ml. The MICs of erythromycin, clarithromycin, azithromycin, josamycin, spiramycin, and the ketolide HMR3004 were then determined and compared. Homogeneous susceptibility patterns were observed for the isolates of the cMLS phenotype (for all but one of the strains, HMR3004 MICs were 0.5 to 8 μg/ml and the MICs of the other drugs were >128 μg/ml) and those of the M phenotype (resistance only to the 14- and 15-membered macrolides was recorded, with MICs of 2 to 32 μg/ml). Conversely, heterogeneous susceptibility patterns were observed in the isolates of the iMLS phenotype, which were subdivided into three distinct subtypes designated iMLS-A, iMLS-B, and iMLS-C. The iMLS-A strains (n = 84) were highly resistant to the 14-, 15-, and 16-membered macrolides and demonstrated reduced susceptibility to low-level resistance to HMR3004. The iMLS-B strains (n = 12) were highly resistant to the 14- and 15-membered macrolides, susceptible to the 16-membered macrolides (but highly resistant to josamycin after induction), and susceptible to HMR3004 (but intermediate or resistant after induction). The iMLS-C strains (n = 24) had lower levels of resistance to the 14- and 15-membered macrolides (with erythromycin MICs increasing two to four times after induction), were susceptible to the 16-membered macrolides (but resistant to josamycin after induction), and remained susceptible to HMR3004, also after induction. The erythromycin resistance genes in 100 isolates of the different groups were investigated by PCR. All cMLS and iMLS-A isolates tested had theermAM (ermB) gene, whereas all iMLS-B and iMLS-C isolates had the ermTR gene (neither methylase gene was found in isolates of other groups). The M isolates had only the macrolide efflux (mefA) gene, which was also found in variable proportions of cMLS, iMLS-A, iMLS-B, and iMLS-C isolates. The three iMLS subtypes were easily differentiated by a triple-disk test set up by adding a josamycin disk to the erythromycin and clindamycin disks of the conventional double-disk test. Tetracycline resistance was not detected in any isolate of the iMLS-A subtype, whereas it was observed in over 90% of both iMLS-B and iMLS-C isolates.
Anti‐ and pro‐oxidant activity of rutin and quercetin derivatives

Some semi‐synthetic flavonoids, particularly derivatives of rutin, are used as therapeutic agents in the treatment of diseases involving free radicals. Here, for the first time, a complete study has been made of the relationship between the structure of such molecules and their superoxide, hydroxyl and peroxyl radical scavenging activity. The molecules chosen for this study were rutin, its aglycone (quercetin), and their methyl ethyl and hydroxyl‐ethyl derivatives. Our results are consistent with the general agreement on the structural requirements for free radical scavenging activity. Moreover, we have shown that alkylation of the hydroxyl in position 7 enhanced the scavenging, and also that in a Fenton reaction system, some quercetin derivatives with free catechol moiety or free hydroxyl in position 3 (or both) were pro‐oxidant, through superoxide radical and hydrogen peroxide production. Although the structural features needed for pro‐oxidant activity are not entirely clear, it appears that to avoid pro‐oxidant behaviour, the hydroxyl group in position 3 should be blocked to prevent its auto‐oxidation. Thus, flavonoids cannot only be considered purely as antioxidants, since under certain reaction conditions they can also display pro‐oxidant activity. This unexpected behaviour could explain, in part, the observed toxicity of some flavonoids in‐vivo.
Modulation of T Cell and Innate Immune Responses by Retinoic Acid

Retinoic acid (RA) is produced by a number of cell types, including macrophages and dendritic cells, which express retinal dehydrogenases that convert vitamin A to its main biologically active metabolite, all-trans RA. All-trans RA binds to its nuclear retinoic acid receptors that are expressed in lymphoid cells and act as transcription factors to regulate cell homing and differentiation. RA production by CD103+ dendritic cells and alveolar macrophages functions with TGF-β to promote conversion of naive T cells into Foxp3+ regulatory T cells and, thereby, maintain mucosal tolerance. Furthermore, RA inhibits the differentiation of naive T cells into Th17 cells. However, Th1 and Th17 responses are constrained during vitamin A deficiency and in nuclear RA receptor α–defective mice. Furthermore, RA promotes effector T cell responses during infection or autoimmune diseases. Thus, RA plays a role in immune homeostasis in the steady-state but activates pathogenic T cells in conditions of inflammation.
EAAP: Efficient Anonymous Authentication With Conditional Privacy-Preserving Scheme for Vehicular Ad Hoc Networks

Providing an efficient anonymous authentication scheme in vehicular ad hoc networks (VANETs) with low computational cost is a challenging issue. Even though, there are some existing schemes to provide anonymous authentication, the existing schemes suffer from high computational cost in the certificate and the signature verification process, which leads to high message loss. Therefore, they fail to meet the necessity of verifying hundreds of messages per second in VANETs. In our scheme, we propose an efficient anonymous authentication scheme to avoid malicious vehicles entering into the VANET. In addition, the proposed scheme offers a conditional tracking mechanism to trace the vehicles or roadside units that abuse the VANET. As a result, our scheme revokes the privacy of misbehaving vehicles to provide conditional privacy in a computationally efficient way through which the VANET entities will be anonymous to each other until they are revoked from the VANET system. Moreover, the proposed scheme is implemented and the performance analysis shows that our scheme is computationally efficient with respect to the certificate and the signature verification process by keeping conditional privacy in VANETs.
Comparative Studies of Evolutionary Responses to Light Environments in Arabidopsis

In this article, we compare the reaction norms to foliage shade (changes in light quality, spatially fine‐grained environmental variation) and photoperiod (day length, spatially coarse‐grained environmental variation) in several haplotypes of Arabidopsis thaliana from Scandinavia. We found that both across‐environment means and phenotypic plasticities evolved continuously and very rapidly within this group. Both character means and trait plasticities were highly integrated, in part as predicted by the adaptive plasticity hypothesis for response to foliage shade (the so‐called shade‐avoidance syndrome). We found that a significant but small fraction of the variance in across‐treatment trait means and plasticities in response to one environmental factor is explained by variation of the same traits in response to the other factor. Genetic relatedness based on chloroplast DNA sequence variation among haplotypes was not associated with variation in across‐treatment character means or their plasticities, suggesting that evolution of these characters has occurred on a local geographic scale via reticulation (outcrossing) among maternal lines rather than by the differential survival of selfing lineages.
IFNgamma deficient C57BL/6 (H-2b) mice develop collagen induced arthritis with predominant usage of T cell receptor Vbeta6 and Vbeta8 in arthritic joints.

BACKGROUND Transgenic deficiency in interferon gamma (IFNgamma) or IFNgamma receptor makes resistant strains of mice bearing H-2(b) or H-2(d) susceptible to collagen induced arthritis (CIA). OBJECTIVE To determine whether the escape from regulation of disease susceptibility at the major histocompatibility complex level involves a new use of autoimmune T cells expressing T cell receptor (TCR) Vbeta that vary from the cell populations previously identified within arthritic joints. METHODS Arthritis was induced by a standard protocol with type II bovine collagen (CII) in complete Freund's adjuvant. Clinical features, histopathology, immunological responses, and TCR profile in arthritic joints in IFNgamma knockout C57BL/6 (B6.IFNgamma KO) mice (H-2(b)) were compared directly with those in DBA/1 mice (H-2(q)). RESULTS 60-80% of B6.IFNgamma KO mice developed a progressive arthritis with a similar clinical course to classical CIA in DBA/1 mice. The affected joints in B6.IFNgamma KO mice had an erosive form of arthritis with similar features to joint disease in DBA/1 mice. B6.IFNgamma KO mice produced significantly higher levels of IgG2b and IgG1 autoantibodies to murine CII and showed increased proliferative response to CII compared with B6 mice. Comparable levels of interleukin 1beta and tumour necrosis factor alpha expression were detected in arthritic joints from beta6.IFNgamma KO and DBA/1 mice. B6.IFNgammaKO mice used predominantly TCR Vbeta6 and Vbeta8 in arthritic joints. This TCR Vbeta profile is similar to that found in DBA/1 mice with CIA. CONCLUSIONS C57BL/6 mice deficient in IFNgamma production can develop arthritis that resembles classical CIA. These data suggest that IFNgamma is a key factor mediating susceptibility to CIA.
Specificity and Regulation of the Endoplasmic Reticulum‐Associated Degradation Machinery

The endoplasmic reticulum‐associated degradation (ERAD) machinery selects native and misfolded polypeptides for dislocation across the ER membrane and proteasomal degradation. Regulated degradation of native proteins is an important aspect of cell physiology. For example, it contributes to the control of lipid biosynthesis, calcium homeostasis and ERAD capacity by setting the turnover rate of crucial regulators of these pathways. In contrast, degradation of native proteins has pathologic relevance when caused by viral or bacterial infections, or when it occurs as a consequence of dysregulated ERAD activity. The efficient disposal of misfolded proteins prevents toxic depositions and persistent sequestration of molecular chaperones that could induce cellular stress and perturb maintenance of cellular proteostasis. In the first section of this review, we survey the available literature on mechanisms of selection of native and non‐native proteins for degradation from the ER and on how pathogens hijack them. In the second section, we highlight the mechanisms of ERAD activity adaptation to changes in the ER environment with a particular emphasis on the post‐translational regulatory mechanisms collectively defined as ERAD tuning.
A new set of monoclonal antibodies against human Fc gamma RII (CD32) and Fc gamma RIII (CD16): characterization and use in various assays.

Four mouse anti-human Fc gamma RII (CD32) (6C4, 2B2, 3D3, 93.4) (IgG1, kappa) and one anti-human Fc gamma RIII (CD16) (7.5.4) IgG1, kappa) MAbs were raised. An in vitro switch variant, 7.5. 4Sw50 (IgG2b, kappa), was also derived from the 7.5. 4 MAb. 6C4, 2B2, and 3D3 MAbs bind both Fc gamma RIIa and Fc gamma RIIb isoforms. Two of them (6C4 and 2B2 MAbs) allow a complete blockade of the binding of immune complexes to Fc gamma RII. All three MAbs immunoprecipitate the receptor and bind both its glycosylated and nonglycosylated forms. The fourth anti Fc gamma RII MAb, 93.4, directed against the intracellular region of Fc gamma RIIa1/2, allows its detection by Western blotting only when it is not phosphorylated. The 7.5. 4 MAb binds both Fc gamma RIIIa and Fc gamma RIIIb, can be used in Western blotting and does not inhibit aggregated IgG binding. ELISA using IV.3 (anti-Fc gamma RIIa1/2)/6C4 and 3G8 (anti-Fc gamma RIIIa/b)/7.5. 4Sw50 MAb pairs make it possible to detect soluble Fc gamma RIIa1/2 and Fc gamma RIII, with a sensitivity of 200 pg/mL and 1 ng/mL, respectively. Surface plasmon resonance analyses indicated that the KD of two of the three anti-Fc gamma RII and of the anti-Fc gamma RIII are in the same order of magnitude (6C4: 0.78 nM, 2B2: 0.28 nM, 7.5.4: 0.47 nM). The anti-Fc gamma RII 3D3 MAb exhibits an off-rate constant higher than the 6C4 and 2B2 MAbs and a KD of 2.19 nM.