Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2

We have previously described HpuAB, a two‐component receptor that mediates binding to haemoglobin (Hb), haemoglobin–haptoglobin (Hb‐Hp) and apo‐haptoglobin (Hp). In this communication, we constructed non‐polar mutations in the hpuA and hpuB loci to examine the individual roles of HpuA and HpuB. Our results indicate that both HpuA and HpuB are required for the acquisition of Fe from Hb and Hb‐Hp. We isolated Hb utilization‐positive (Hb+) variants of our Hb utilization‐negative (Hb−) hpu mutants at a frequency of 10−3 and demonstrated that the Hb+ phenotype resulted from the expression of a second Hb receptor, HmbR. Expression of HmbR in DNM2 was found to be controlled by translational frameshifting involving a polyguanine (G) tract located within the hmbR locus. The hpuA locus also contains a poly(G) tract, which suggested that meningococci could phase vary each Hb receptor independently by slip‐strand mispairing in the poly(G) tracts found in hpuA and hmbR. Thus, we isolated a naturally occurring Hb− variant of DNM2, designated DNM2 Hb−, which did not express either HpuAB or HmbR. Hb+ variants of DNM2Hb− were selected and examined for HpuAB and HmbR expression. In each instance, acquisition of HpuAB or HmbR expression was correlated with phase variation in the poly(G) tract of each Hb receptor.
In Vivo mouse imaging and spectroscopy in drug discovery

Imaging modalities such as micro‐computed tomography (micro‐CT), micro‐positron emission tomography (micro‐PET), high‐resolution MRI, optical imaging, and high‐resolution ultrasound have become invaluable tools in preclinical pharmaceutical research. They can be used to non‐invasively investigate, in vivo, rodent biology and metabolism, disease models, and pharmacokinetics and pharmacodynamics of drugs. The advantages and limitations of each approach usually determine its application, and therefore a small‐rodent imaging laboratory in a pharmaceutical environment should ideally provide access to several techniques. In this paper we aim to illustrate how these techniques may be used to obtain meaningful information for the phenotyping of transgenic mice and for the analysis of compounds in murine models of disease. Copyright © 2007 John Wiley & Sons, Ltd.
Initial experience with paclitaxel-coated stents.

Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology that is supposed to inhibit in-stent restenosis, thus providing a biological and mechanical solution. This technique is a very promising. To date, several agents have been used, including paclitaxel, QP-2, rapamycin, actinomycin D, dexamethason, tacrolimus, and everolimus. Several studies, published recently or still ongoing, have evaluated these drugs as to their release kinetics, effective dosage, safety in clinical practice, and benefit. These studies include: SCORE (paclitaxel derivative), TAXUS I-VI, ELUTES, ASPECT, DELIVER (paclitaxel), RAVEL, SIRIUS (sirolimus), ACTION (actinomycin), EVIDENT, PRESENT (tacrolimus), EMPEROR (dexamethason), and FUTURE (everolimus). Paclitaxel was one of the first stent-based antiproliferative agents under clinical investigation that provided profound inhibition of neointimal thickening depending on delivery duration and drug dosage. The randomized, multicenter SCORE trail (Quanam stent, paclitaxel-coated) enrolled 266 patients at 17 sites. At 6-month's follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs 36.9% control group), which was attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to frequent stent thrombosis and side-branch occlusions, the reported 30-day MACE rate was 10.2%. The randomized TAXUS-I safety trial (BSC, NIRx, paclitaxel-coated) also demonstrated beneficial reduction of restenotic lesions at 6-month's follow-up (0% vs 10%) but was associated with the absence of thrombotic events presumably due to less drug dosage. The ongoing TAXUS II-VI trials are addressing additional insight regarding the efficacy of the TAXUS paclitaxel-eluting stent. ASPECT and ELUTES evaluated paclitaxel-coated stents (i.e., Cook and Supra G), including subgroups with different drug dosages. With respect to stent restenosis and neointimal proliferation, both studies demonstrated a clear dose response. The RAVEL and the SIRIUS trials evaluated sirolimus-coated stents (i.e., Cordis, Johnson & Johnson, and Bx VELOCITY stents). Results confirmed the beneficial findings regarding reduction of renarrowing using a drug-eluting stent without any major adverse effects. Although parameters such as drug toxicity, optimal drug dosage, or delayed endothelial healing still need to be evaluated, today's clinical experience indicates that drug-coated stents are extremely beneficial in the interventional treatment of coronary lesions.
Olanzapine- and Clozapine-induced Stuttering

Drug-induced stuttering has been described in association with several drugs, in particular antidepressants and low-potency neuroleptics. Here we describe a case series of stuttering induced by the atypical neuroleptics olanzapine and clozapine. Patients receiving neuroleptic treatment were carefully screened for stuttering as a possible side effect. We have studied all patients in the outpatient department (800 per year) as well as most inpatients (1300 per year) within 3 years. Seven cases of drug-induced stuttering were observed. Six patients suffered from stuttering in association with olanzapine treatment, and one received clozapine. Stuttering arose on average 2-21 days after initiation of treatment and ceased 2-5 days after discontinuation. Most patients suffered from additional diseases, such as brain pathology due to cortical atrophy or celiac disease, or received concomitant medication (i.e. intrathecal morphine pump). Our case series suggests that the atypical neuroleptic olanzapine can induce stuttering in the absence of a history of stuttering without accompanying akathisia or general decline of function. It appears that preexisting brain pathology or concomitant anti-depressant medication might predispose some patients to this side effect.
Degradation of polychlorinated biphenyls by two species of Achromobacter.

Two species of Achromobacter were isolated from sewage effluent using biphenyl (BP) and p-chlorobiphenyl (pCB) respectively as sole carbon sources. Achromobacter BP grown on biphenyl accumulated a product with an ultraviolet absorption maximum at 257 nm which could not be identified. Washed cell suspensions of both isolates oxidized biphenyl, o-phenylphenol, phenylpyruvate, catechol, p-chlorobiphenyl, m-chlorobiphenyl, o-chlorobiphenyl, o,o′-dichlorobiphenyl, and p,p′-dichlorobiphenyl. Both isolates produced meta cleavage products by fission of the benzene ring. However, spectral characteristics of degradation products from respective substrates were different between the two isolates, indicating divergent degradation pathways. Benzoic and p-chlorobenzoic acids were produced from the degradation of BP and pCB, respectively, by Achromobacter pCB. Chloride was not produced by either isolate during the degradation of all chlorobiphenyls tested including the growth of Achromobacter pCB on p-chlorobiphenyl.
HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy

Objective:To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Design:Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Methods:Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. Results:We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin αvβ3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. Conclusion:The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.
Design of discrete-time linear-quadratic regulator with optimal observer

It is shown that by means of an appropriate choice of the coefficients of the regulator of the order smaller by one from that of the plant, it is possible to obtain the freely prescribed poles of the discrete-time (DT), closed loop (CL) system. The algorithm of design of the regulator-observer for the DT CL system with output feedback is described. The resulting CL system retains all the poles of the CL system with linear-quadratic regulator and state feedback and has additionally the freely chosen poles coming from the observer. It is also shown that the designed regulator is the same as that based on the Luenberger observer; the latter is optimal for adequate initial conditions. For the systems with stepwise excitations of the plant output, the deterministic equivalence principle has been proved true.
Formation of formaldehyde and peroxides by air oxidation of high purity polyoxyethylene surfactants

Ethoxylated alcohols are non‐ionic surfactants. The majority are used in household cleaners, laundry products, toiletries and in industrial and institutional cleaners. In previous studies, an ethoxylated non‐ionic surfactant of technical quality showed allergenic activity in guinea pig experiments. Chemical analysis revealed a content of formaldehyde, a well‐known contact allergen, and peroxides in the surfactant. Most cases of occupational contact dermatitis are considered to be of irritant origin, caused by contact with water and surfactants, but if allergenic autoxidation products can be formed, allergic contact dermatitis cannot be excluded. The sensitizing potential of a chemically defined high purity ethoxylated alcohol was investigated and oxidation under various storage and handling conditions was studied for this and a homologous product. The pure surfactant showed no significant allergenic activity on predictive testing in guinea pigs. When ethoxylated alcohols were stored in the refrigerator, their deterioration was limited. At room temperature, their content of peroxides and formaldehyde increased with time. Levels of formaldehyde above those capable of causing positive patch test reactions were found. Since such surfactants have wide applications, resulting exposure to formaldehyde could be more frequent than is generally realized, contributing to persistence of dermatitis in individuals allergic to formaldehyde.
DISENO, REALIZACION Y EVALUACION DE UN SISTEMA DE VALIDACION DEL RENDIMIENTO DEL EJERCICIO MEDICO BASADO EN LA AUTOPSIA EN EL HOSPITAL UNIVERSITARIO DE SANTANDER

Se planteo como meta crear un sistema bioinformatico que permitiera realizar analisis complejos de facil manipulacion, y evaluar el rendimiento diagnostico premortem en los pacientes sometidos a autopsia en el HUS durante los anos 2005 a 2008. Para la realizacion de estos objetivos se creo el SIRAHUS, herramienta que permite registrar y evaluar grandes volumenes de datos, mediante un entorno de facil manipulacion, con capacidad de recodificacion a ambientes de analisis de alta complejidad. Para probar este sistema, y desarrollar el segundo objetivo se realizo un estudio analitico de evaluacion diagnostica multiple. Fueron analizadas 494 autopsias, 208 no perinatales y 286 perinatales, realizadas en pacientes provenientes de 34 municipios localizados en 6 departamentos y dos paises. El rango de edad de los pacientes evaluados se encontro entre 12 semanas de gestacion a 94 anos, el rendimiento diagnostico fue en: enfermedades infecciosas (LR+ 7.87, LR- 0.41), enfermedades Neoplasicas (LR+ 11.47, LR- 0.51), enfermedades endocrinas y Metabolicas (LR+ 18.3, LR- 0.51), enfermedades del sistema nervioso central (LR+ 7.27, LR- 0.78), enfermedades cardiovasculares (LR+ 7.29, LR- 0.68), enfermedades del sistema respiratorio (LR+ 73.61, LR- 0.93), enfermedades del aparato digestivo (LR+ 7.61, LR- 0.71), enfermedades de la piel (LR+ 12.25, LR- 0.83), enfermedades del embarazo y puerperio (LR+ 4.16, LR- 0.59), enfermedades perinatales (LR+ 4.91, LR- 0.46), malformaciones y deformidades (LR+ 27.07, LR- 0.48), y otros diagnosticos (LR+ 3.34, LR- 0.87). En conclusion, se produjo una herramienta versatil con capacidad de evaluacion de datos de alta complejidad, innovadora en sus especificaciones y capacidad, y se caracterizo una extensa poblacion de pacientes sometidos a autopsia, sus hallazgos y alteraciones, finalmente se logro evaluar el ejercicio clinico, con parametros operativos altamente detallados, se identifico sus errores, y se estratifico por servicios y caracteristicas de la enfermedad, hecho sin precedentes a nivel global.
Glucocorticoid-inducible retrovector for regulated transgene expression in genetically engineered bone marrow stromal cells.

Transplantable bone marrow stromal cells can be utilized for cell therapy of mesenchymal disorders. They can also be genetically engineered to express synthetic transgenes and subsequently serve as a platform for systemic delivery of therapeutic proteins in vivo. Inducible production of therapeutic proteins would markedly enhance the usefulness of stromal cells for cell therapy applications. We determined whether synthetic corticosteroid hormones can be used to tightly control transgene expression via the glucocorticoid response pathway in primary bone marrow stromal cells. This regulatory mechanism does not require the presence of potentially immunogenic prokaryotic or chimeric "Trans-activators. " Further, synthetic corticosteroids are pharmaceutical agents that can be readily used in vivo. We designed a self-inactivating retroviral vector in which expression of the green fluorescent protein (GFP) reporter is controlled by a minimal synthetic promoter composed of five tandem glucocorticoid response elements upstream of a TATAA box. Vesicular stomatitis virus G-pseudotyped retroparticles were synthesized and utilized to transduce cultured cell lines and primary rat bone marrow stromal cells. We have shown that primary rat bone marrow stromal cells could be efficiently engineered with our GRE-containing retrovector, basal reporter expression was low in the absence of exogenous synthetic corticosteroids, and GFP expression was dexamethasone inducible and reversible. To summarize, this strategy allows dexamethasone-induced, "on-demand" transgene expression from transplantable genetically engineered bone marrow stromal cells.
A longitudinal investigation of the role of self-medication in the development of comorbid mood and drug use disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

OBJECTIVE To examine whether self-medication with drugs confers risk of comorbid mood and drug use disorders. METHOD A longitudinal, nationally representative survey was conducted by the National Institute on Alcohol Abuse and Alcoholism. The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) assessed DSM-IV-TR psychiatric disorders, self-medication, and sociodemographic variables at 2 time points. A total of 34,653 adult, US participants completed both waves of the survey. Wave 1 was conducted between 2001 and 2002, and Wave 2 interviews took place 3 years later (2004-2005). Logistic regression and population attributable fractions were calculated to obtain estimates of the association between self-medication and incident disorders. RESULTS Logistic regression analyses revealed that self-medication with drugs conferred a heightened risk of new-onset drug dependence among those with baseline mood disorders (adjusted odds ratio [AOR] = 7.65; 95% CI, 3.70-15.82; P < .001) and accounted for over 25% of incident drug dependence disorders among people with mood disorders. Among those with comorbid mood and drug use disorders at baseline, self-medication with drugs was associated with the persistence of drug abuse (AOR = 2.47; 95% CI, 1.34-4.56; P < .01), accounting for over one-fifth of the persistence of drug use disorders at 3-year follow-up. CONCLUSIONS Self-medication with drugs among individuals with mood disorders confers substantial risk of developing incident drug dependence and is associated with the persistence of comorbid mood and drug use disorders. These results clarify a pathway that may lead to the development of mood and drug use disorder comorbidity and indicate an at-risk population, with potential points of intervention for prevention of comorbidity.
Projection of reconstructed single purkinje cell axons in relation to the cortical and nuclear aldolase C compartments of the rat cerebellum

Although the overall topography of the cerebellar corticonuclear projection formed by Purkinje cell (PC) axons has been described, only a few studies have dealt with the organization of this projection at the level of individual PC axons. Thus, we reconstructed 65 single PC axons that were labeled with biotinylated dextran amine in the rat. We then analyzed the relationship between the projections of these PCs and the compartmentalization of the cerebellar cortex and nuclei based on the topography of olivocerebellar projection and aldolase C expression in PCs. After giving rise to short local recurrent collaterals near the soma, a PC axon formed a terminal arbor in a specific small area in the cerebellar nuclei (CN). The terminal arbors of vermal PCs were spread more widely than those of hemispheric PCs and sometimes extended to extracerebellar targets. PCs located in any of the aldolase C‐positive (Groups I and II) and ‐negative (Groups III and IV) stripes consistently projected to the caudoventral and rostrodorsal parts of the CN, respectively, precisely in accordance with the compartmentalization of the cortex and nuclei. Mediolateral segregation and rostrocaudal convergence were seen between projections of separate PCs in a single aldolase C compartment. The results revealed a tight link between the projection patterns of individual PC axons, the topography of the olivocerebellar pathway, and the aldolase C expression pattern. Their overall correspondence seems to reflect a basic aspect of cerebellar organization, although some area‐dependent variation in the relationship of these three entities was also present. J. Comp. Neurol. 512:282–304, 2009. © 2008 Wiley‐Liss, Inc.
1 Alpha,25-dihydroxycholecalciferol receptors in intestine. II. Temperature-dependent transfer of the hormone to chromatin via a specific cytosol receptor.

Abstract Specific binding of 1α,25-dihydroxycholecalciferol in the cytosol and purified chromatin fractions of chick small intestinal mucosa was studied to investigate the mechanism by which this hormone arrives at its chromatin binding site. The cytosol fraction of the mucosa contains a macromolecule with a high affinity (Kd = 2.2 x 10-9 m) for 1α,25-dihydroxycholecalciferol and has a limited number of binding sites which are saturated at low hormone concentrations (≃ 10-8 m). The association of the sterol with the cytoplasmic component is thermolabile, and is destroyed by treatment with pronase, but not by nucleases, and the receptor component is therefore presumed to be a protein. The protein-sterol complex was isolated and characterized by sucrose gradient centrifugation and sediments at 3 to 3.5 S in the presence of 0.15 m KCl. The interaction of 1α,25-dihydroxy[3H] cholecalciferol with the cytosol protein is reversed by unlabeled 1α,25-dihydroxycholecalciferol g 25-hydroxycholecalciferol g 1α,25-hydroxycholecalciferol g cholecalciferol ≃ estradiol-17β. The subcellular localization of 1α,25-dihydroxycholecalciferol is temperature-dependent. The hormone remains bound to the cytosol fraction at 0° in whole intestines in vitro, and a dramatic movement of 1α,25-dihydroxycholecalciferol to the nuclear chromatin occurs at 37°. The temperature dependence of the hormone localization is also evident in intestinal mucosa homogenates and reconstituted cytosol-chromatin systems. This observation suggests that the cell membrane and nuclear membrane are not involved in the temperature-dependent process. It is postulated that the specific cytosol receptor for 1α,25-dihydroxycholecalciferol functions to transport the hormone to its ultimate site of action in the nuclear chromatin.
Potential of hazelnut husks as a broiler litter material

1. Hazelnut husks and some other litter materials were compared for litter properties and their effects on broiler performance. 2. A total of 750 1-d-old broiler chicks were weighed and assigned at random to 1 of 5 treatments, with each treatment replicated 3 times. 3. The treatments were wood shavings (control), wheat stalks, rice hulls, hazelnut husks, and a mixture of 50% rice hulls and 50% hazelnut husks. 4. Although hazelnut husks were associated with lower body weights at 49 d of age, food efficiency,mortality, carcase yield, breast blisters and production index were similar to birds on wood shavings. Hazelnut husks had the highest litter moisture. 5. The results show that hazelnut husks alone and when mixed with rice hulls are a potential alternative litter material for broiler production.
Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

Abstract Self-emulsifying drug delivery system (SEDDS) is an isotropic mixture of lipid, surfactant and co-surfactant, which forms a fine emulsion when comes in contact of an aqueous medium with mild agitation. SEDDS is considered as a potential platform for oral delivery of hydrophobic drug in order to overcome their poor and irregular bioavailability challenges. In spite of fewer advantages like improved solubility of drug, bypassing lymphatic transport etc., SEDDS faces different controversial issues such as the use of appropriate terminology (self-microemulsifying drug delivery system; SMEDDS or self-nanoemulsifying drug delivery system; SNEDDS), presence of high amount of surfactant, correlation of in vitro model to in vivo studies, lack of human volunteer study and effect of conversion of SEDDS to final administrable dosage form on pharmacokinetic behavior of the drug. In this review, potential issues or questions on SEDDS are identified and summarized from the pharmacokinetic point of view. Primarily this review includes the conflict between the influences of droplet size, variation in correlation between in vitro lipolysis or ex-vivo intestinal permeation and pharmacokinetic parameters, variation in in vivo results of solid and liquid SEDDS, and potential challenges or limitation of pharmacokinetic studies on human volunteers with orally administered SEDDS. In the past decades, hundreds of in vivo studies on SEDDS have been published. In the present study, only the relevant article on in vivo pharmacokinetic studies with orally administered SEDDS published in past 5–6 years are analyzed for an up to date compilation.