Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression Islands Clustered on the Symbiosis Island of the Mesorhizobium loti Genome

ABSTRACT Rhizobia are symbiotic nitrogen-fixing soil bacteria that are associated with host legumes. The establishment of rhizobial symbiosis requires signal exchanges between partners in microaerobic environments that result in mutualism for the two partners. We developed a macroarray for Mesorhizobium loti MAFF303099, a microsymbiont of the model legume Lotus japonicus, and monitored the transcriptional dynamics of the bacterium during symbiosis, microaerobiosis, and starvation. Global transcriptional profiling demonstrated that the clusters of genes within the symbiosis island (611 kb), a transmissible region distinct from other chromosomal regions, are collectively expressed during symbiosis, whereas genes outside the island are downregulated. This finding implies that the huge symbiosis island functions as clustered expression islands to support symbiotic nitrogen fixation. Interestingly, most transposase genes on the symbiosis island were highly upregulated in bacteroids, as were nif, fix, fdx, and rpoN. The genome region containing the fixNOPQ genes outside the symbiosis island was markedly upregulated as another expression island under both microaerobic and symbiotic conditions. The symbiosis profiling data suggested that there was activation of amino acid metabolism, as well as nif-fix gene expression. In contrast, genes for cell wall synthesis, cell division, DNA replication, and flagella were strongly repressed in differentiated bacteroids. A highly upregulated gene in bacteroids, mlr5932 (encoding 1-aminocyclopropane-1-carboxylate deaminase), was disrupted and was confirmed to be involved in nodulation enhancement, indicating that disruption of highly expressed genes is a useful strategy for exploring novel gene functions in symbiosis.
Age-related association between body mass index and blood pressure: the Humboldt Study.

OBJECTIVE To investigate how age modifies the relation between body mass and blood pressure. DESIGN Community based cross-sectional study. SUBJECTS 2865 residents aged 6 to 74 years (85.6% of the target population) in the town of Humboldt, Saskatchewan, Canada. MEASUREMENTS Body mass index [weight (kg)/height (meters)2], and diastolic and systolic blood pressures. RESULTS Among the subjects, 99.6% were of Caucasian origin. With both sexes, there was a stronger relation between body mass index and diastolic blood pressure in younger age groups than older age groups. In males, the increase in mean blood pressure for a 1-unit increase in body mass index (kg/m2) was 0.72, 0.72, 0.41 and 0.47 mm Hg in the 6-14, 15-34, 35-54 and 55-74 year age groups respectively. In females, the correspondent increase was 0.95, 0.57, 0.46 and 0.43 mm Hg. In females, age also modified the relation between body mass index and the prevalence of high blood pressure. The odds ratios for high blood pressure for a 1-unit increase in body mass index in females was 1.33, 1.21, 1.12 and 1.10 in the 6-14, 15-34, 35-54 and 55-74 year age groups. CONCLUSION Age significantly modifies the relations of body mass index with mean diastolic blood pressure in both sexes, and with the prevalence of high blood pressure in females. The relations are stronger in children and young adults than in older persons.
Prospective cohort study to test the predictability of the Cardiff and Vale paediatric early warning system

Objective: To develop and test the predictability of a paediatric early warning score to identify children at risk of developing critical illness. Design: Prospective cohort study. Setting: Admissions to all paediatric wards at the University Hospital of Wales. Outcome measures: Respiratory arrest, cardiac arrest, paediatric high-dependency unit admission, paediatric intensive care unit admission and death. Results: Data were collected on 1000 patients. A single abnormal observation determined by the Cardiff and Vale paediatric early warning system (C&VPEWS) had a 89.0% sensitivity (95% CI 80.5 to 94.1), 63.9% specificity (95% CI 63.8 to 63.9), 2.2% positive predictive value (95% CI 2.0 to 2.3) and a 99.8% negative predictive value (95% CI 99.7 to 99.9) for identifying children who subsequently had an adverse outcome. The area under the receiver operating characteristic curve for the C&VPEWS score was 0.86 (95% CI 0.82 to 0.91). Conclusion: Identifying children likely to develop critical illness can be difficult. The assessment tool developed from the advanced paediatric life support guidelines on identifying sick children appears to be sensitive but not specific. If the C&VPEWS was used as a trigger to activate a rapid response team to assess the child, the majority of calls would be unnecessary.
[A randomized single blind study of the efficacy of pregabalin in the treatment of opioid withdrawal syndrome].

AIM To study the efficacy and safety of pregabalin (lyrica) in the complex treatment of opioid withdrawal syndrome (OWS). MATERIAL AND METHODS STUDY DESIGN single-blind randomized symptom-triggered protocol with an active control. Thirty-four patients were randomly assigned to two groups. The first group (n=19) received up to 600 mg a day of pregabalin for six days along with symptomatic therapy (basic and symptom-triggered). The second group (n=15) received up to 600 micrograms of clonidine a day as the main treatment along with the same basic and symptomatic regimen. Opiate withdrawal severity, craving, sleep disturbance, anxiety and depression, as well as general clinical impressions and side-effects were assessed daily using internationally validated quantitative psychometric instruments. RESULTS In the pregabalin group, 15 out of 19 (79%) patients completed treatment compared to 7 out of 15 (47%) patients in the clonidine group (p=0.05; Fisher exact test). There were no statistically significant differences between groups on any assessments of the severity of OWS (reduction of the severity of opiate withdrawal), perhaps because of the small sample size. In the pregabalin group, there were lower indicators of the severity of craving for opiates (p=0.05), anxiety (p=0.05) and depression (p<0.05), while patient-rated self-assessment of their general health condition was significantly better compared to the second group (p<0.05). There were no significant differences in the frequency of adverse events between the groups, though the better tolerability of treatment was noted in the pregabalin group. CONCLUSION Treatment regimen of OWS with pregabalin is effective and safe and patients tolerate it better that leads to a higher detoxification completion rate (retention).
Loss of Self-Tolerance to ICA69 in Nonobese Diabetic Mice

Islet cell antigen p69 (ICA69) is a target autoantigen in IDDM. Studies of T-cells from newly diabetic children suggested possible antigenic mimicry between human ICA69 (in particular the Tep69 T-cell epitope, aa 36-47) and the ABBOS region in bovine serum albumin (BSA; aa 152-169), one of several cow's milk proteins that evoke abnormal immunity in diabetes-prone hosts. We recently found the sequence of Tep69 regions to be identical in the four alternatively spliced human and rodent ICA69 isoforms. Immunization of nonobese diabetic (NOD) mice with BSA or ICA69 generates fully cross-reactive T-cell responses to both Tep69 and ABBOS as the immunodominant, naturally generated, and presented T-cell mimicry epitopes. Such responses are absent or weak in healthy strains of mice. NOD mouse recipients of adoptive spleen cell grafts from diabetic donors spontaneously generate easily detectable pools of T-cells specific for ICA69/BSA, as well as the unrelated GAD65. NOD mice injected neonatally with ABBOS or Tep69 show cross-tolerance, but ABBOS-induced tolerance is transient. Neonatal injection of Tep69 reduces disease incidence (23 vs. 68% IDDM, P < 0.02), while neonatal injection of ABBOS has little effect. In contrast, systemic immunization of young NOD females with ABBOS (but not Tep69) reduces the diabetes incidence and delays disease expression, with protected mice generating ABBOS-specific T-cell repertoires unable to recognize the Tep69 mimicry antigen. Our observations demonstrate a loss of self-tolerance to ICA69 in NOD mice, and they establish antigenic mimicry between the two T-cell epitopes in ICA69 and BSA. Further studies are necessary to understand the molecular basis of this mimicry and how either T-cell peptide can modify the disease course.
Family history of depression is associated with younger age of onset in patients with recurrent depression

Background Genetic epidemiology data suggest that younger age of onset is associated with family history (FH) of depression. The present study tested whether the presence of FH for depression or anxiety in first-degree relatives determines younger age of onset for depression. Method A sample of 1022 cases with recurrent major depressive disorder (MDD) was recruited at the Max Planck Institute and at two affiliated hospitals. Patients were assessed using the Schedules for Clinical Assessment in Neuropsychiatry and questionnaires including demographics, medical history, questions on the use of alcohol and tobacco, personality traits and life events. Survival analysis and the Cox proportional hazard model were used to determine whether FH of depression signals earlier age of onset of depression. Results Patients who reported positive FH had a significantly earlier age of onset than patients who did not report FH of depression (log-rank=48, df=1, p<0.0001). The magnitude of association of FH varies by age of onset, with the largest estimate for MDD onset before age 20 years (hazard ratio=2.2, p=0.0009), whereas FH is not associated with MDD for onset after age 50 years (hazard ratio=0.89, p=0.5). The presence of feelings of guilt, anxiety symptoms and functional impairment due to depressive symptoms appear to characterize individuals with positive FH of depression. Conclusions FH of depression contributes to the onset of depression at a younger age and may affect the clinical features of the illness.
Low tolerance to simulated herbivory in Hawaiian seedlings despite induced changes in photosynthesis and biomass allocation.

BACKGROUND AND AIMS Seedling herbivory is an important factor underlying plant community diversity and structure. While considerable research has characterized seedling defence in terms of resistance, very little is known about seedling tolerance of herbivory. Moreover, few studies have attempted to identify mechanisms of tolerance across a range of plant species. METHODS Seedling tolerance of simulated herbivory was tested in a diverse pool of ten Hawaiian plant species, including several lobeliad species (family Campanulaceae), a grass, a herb and common woody trees and shrubs. Tolerance was measured as the relative survival and growth of damaged plants receiving 50 % defoliation with simultaneous jasmonic acid application compared with undamaged control plants, assessed 1·5 and 5 weeks after damage. Putative mechanisms of tolerance were measured, including photosynthetic parameters, light use efficiency, and biomass allocation reflecting growth priorities, and analysed using species-level regression analyses on tolerance indices. KEY RESULTS No species fully tolerated 50 % defoliation at either harvest date, and simulated herbivory significantly reduced shoot as well as root biomass. Lobeliad species had particularly low tolerance. Species varied considerably in size, biomass allocation parameters and their constitutive (pre-damage) and induced (post-damage) photosynthetic parameters. However, only constitutive levels of non-photochemical quenching were significantly related to tolerance, indicating that species with more efficient light use (and less heat dissipation) are better at tolerating damage than species with high levels of heat dissipation. CONCLUSIONS Native Hawaiian plants expressed low tolerance to a conservative level of simulated herbivory. Root growth decreased in response to damage, but this was not associated with greater tolerance, suggesting this response may be due to allocation constraints following defoliation and not due to adaptive plasticity. Conservation of native island plants threatened by invasive herbivores should prioritize protection for seedlings for improved regeneration and the persistence of native plants in disturbed habitats.
Rat cerebral cortex corticotropin‐releasing hormone receptors: evidence for receptor coupling to multiple G‐proteins

The wide distribution of corticotrophin‐releasing hormone (CRH) receptors in brain and periphery appear to be important in integrating the responses of the brain, endocrine and immune systems to physiological, psychological and immunological stimuli. The type 1 receptors are highly expressed throughout the cerebral cortex, a region involved in cognitive function and modulation of stress responses, where they are coupled to the adenylyl cyclase system. Using techniques that analyse receptor‐mediated guanine‐nucleotide binding protein (G‐proteins) activation, we recently demonstrated that expressed type 1α CRH receptors are capable of activating multiple G‐proteins, which suggests that CRH can regulate multiple signalling pathways. In an effort to characterize the intracellular signals generated by CRH in the rat cerebral cortex we sought to identify G‐proteins activated by CRH in a physiological membrane environment. Rat cerebral cortical membrane suspensions were analysed for the ability of CRH to stimulate incorporation of [α‐32P]‐GTP‐γ‐azidoanilide to various G‐protein α‐chains. Our results show that CRH receptors are coupled to and activate at least five different G‐proteins (Gs, Gi, Gq/11, Go and Gz) with subsequent stimulation of at least two intracellular signalling cascades. In addition, the photoaffinity experiments indicated that the CRH receptors preferentially activate the 45 kDa form of the Gsα‐protein. This data may help elucidate the intracellular signalling pathways mediating the multiple actions of CRH especially under different physiological conditions.
Short dysfunctional telomeres impair the repair of arsenite‐induced oxidative damage in mouse cells

Telomeres and telomerase appear to participate in the repair of broken DNA ends produced by oxidative damage. Arsenite is an environmental contaminant and a potent human carcinogen, which induces oxidative stress on cells via the generation of reactive oxygen species affecting cell viability and chromosome stability. It promotes telomere attrition and reduces cell survival by apoptosis. In this study, we used mouse embryonic fibroblasts (MEFs) from mice lacking telomerase RNA component (mTERC−/− mice) with long (early passage or EP) and short (late passage or LP) telomeres to investigate the extent of oxidative damage by comparing the differences in DNA damage, chromosome instability, and cell survival at 24 and 48 h of exposure to sodium arsenite (As3+; NaAsO2). There was significantly high level of DNA damage in mTERC−/− cells with short telomeres as determined by alkaline comet assay. Consistent with elevated DNA damage, increased micronuclei (MN) induction reflecting gross genomic instability was also observed. Fluorescence in situ hybridization (FISH) analysis revealed that increasing doses of arsenite augmented the chromosome aberrations, which contributes to genomic instability leading to possibly apoptotic cell death and cell cycle arrest. Microarray analysis has revealed that As3+ treatment altered the expression of 456 genes of which 20% of them have known functions in cell cycle and DNA damage signaling and response, cell growth, and/or maintenance. Results from our studies imply that short dysfunctional telomeres impair the repair of oxidative damage caused by arsenite. The results will have implications in risk estimation as well as cancer chemotherapy. J. Cell. Physiol. 214: 796–809, 2008. © 2007 Wiley‐Liss, Inc.
Allergen avoidance in the primary prevention of asthma

Purpose of reviewSix primary prevention studies trialing environmental modifications to reduce asthma in children have published results of clinical outcomes. All are still in progress. Recent findingsIn the Isle of Wight study, mite and food avoidance were evaluated to age 9 months. At 8 years, children in the active group had less current wheeze, wheeze with bronchial hyperresponsiveness and atopy (P⩽0.05). The Canadian Primary Prevention Study examined avoidance of inhalant and food allergens. At 1 year there was a reduction in probable asthma and rhinitis in the active group. The Study on the Prevention of Allergy in Children in Europe tested avoidance of inhalant and food allergens. At 1 year there was less atopy and sensitization to mites in the active group. In the Childhood Asthma Prevention Study both mite avoidance and a dietary supplement of omega 3 fatty acids were analysed in a factorial design. At age 18 months, children in the dietary intervention group had significantly less wheeze. Eczema was more common amongst children using the mite avoidance measures. The Prevention and Incidence of Asthma and Mite Allergy Study is a placebo-controlled study of mite avoidance. At 2 years, there was a small reduction in nocturnal cough without a cold in the active group. The Manchester Asthma and Allergy Study included stringent environmental control. At 1 year prescribed medication for wheeze and wheeze with shortness of breath were significantly less common in the active group than the control group. SummaryAlthough initial results look promising, further follow up of the ongoing cohorts is required before any recommendations can be made within the public health context.
Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature

Deficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed ‘autoimmune thrombotic thrombocytopenic purpura’. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2–3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors.
Evidence of involvement of the human Par-4 (PAWR) gene in major depressive disorder

Abstract Qbjectives. The aim of the study was to examine the associations between genetic variations in the human PAWR gene and major depressive disorder (MDD) as well as the response to antidepressant treatment. Methods. Six-hundred and two patients with MDD and 543 controls were included in the study; among the MDD patients, 268 were followed-up for a further 8 weeks in order to assess their response to treatment with selective serotonin reuptake inhibitors (SSRIs). Six polymorphisms (rs17005769, rs4842318, rs7305141, rs2307223, rs8176874 and rs2307220) of the PAWR gene were investigated with regard to their association with MDD and antidepressant treatment efficacy. Results. One polymorphism, rs8176874, was in genotypic (uncorrected P = 0.005) and allelic (uncorrected P = 0.0015) association with MDD. Several haplotypes spanning rs7305141–rs2307223–rs8176874 were also significantly associated with MDD after correction for multiple testing (corrected P < 0.05). However, neither single-marker nor haplotype-based analyses suggested an association between the studied markers and SSRI treatment response. Conclusions. Genetic variations in the PAWR gene are related to susceptibility to MDD but not to SSRI treatment response.
Influence of Azadirachtin, a Botanical Insecticide, on Chrysoperla carnea (Stephens) Reproduction: Toxicity and Ultrastructural Approach

Abstract A commercial formulation of azadirachtin (Align) was tested on Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae) adults to determine its effects on reproduction. Three methods of exposure were carried out in the laboratory (residual, direct contact and ingestion) with concentrations close to the maximum field recommended concentration in Spain (48 mg AI/liter). Align proved to be harmless to newly emerged adults irrespective of the mode of exposure. Nevertheless, fecundity was reduced in a reversible way in females that have ingested azadiracthin after the onset of oviposition. Fertility was not different from that of controls in all treatments. Additional tests showed that males were not involved in the reduction of oviposition. Electron microscopy studies pointed out that Align interfered with vitellogenin synthesis and/or its uptake by developing oocytes; thus, growing follicles in treated females were significantly smaller that those of the controls. The role of azadirachtin as a compound that may influence several hormonal and protein titers involved in reproduction is also discussed. RESUMEN Align, formulación comercial de la Azadiractina, se ensayó en adultos de Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae) para determinar su posible efecto en la reproducción. Se estudiaron tres métodos de exposición diferentes (contacto residual y tópico e ingestión) con concentraciones próximas a las de campo (48 mg i.a./liter). Align no es tóxico en adultos recién emergidos independientemente del tipo de ensayo realizado. Sin embargo, la azadiractina redujo la fecundidad de forma reversible en las hembras que habían ingerido el insecticida solamente cuando éstas ya habían comenzado la oviposición. La fertilidad en las hembras tratadas no difirió de los testigos en ninguno de los tratamientos realizados. Ensayos adicionales mostraron que los machos no eran responsables de la reducción de la oviposición. Los estudios de microscopía electrónica apuntaron a una interferencia del insecticida con la síntesis de vitelogenina y/o su absorción por los oocitos en desarrollo. Los folículos en desarrollo de las hembras tratadas eran de menor tamaño que los de los testigos. En este trabajo se discute el papel del insecticida como un compuesto que podría influir en las concentraciones de hormonas y proteínas que intervienen en la reproducción.
Response surface optimization of bioethanol production based on process simulation of distillation

Distillation is the most widely used separation operation in chemical industries. The great consumption of energy is the major disadvantage of this process that is unable to reach a high level of purity of bioethanol. The objective of this study is to optimize the distillation column. A sensitivity studies were performed by response surface methodology (RSM) according to the principles of central composite design (CCD) to examine the effects of reflux ratio and feeding tray of distillation column on the production of bioethanol and consumption energy. The results of this study show that the optimum production of ethanol predicted by model is 90%, for a reflux rate of 6.9, and the feeding tray number of the column is rounded to 15.
Assessing the impact of national guidelines on the management of children hospitalized for acute bronchiolitis

Acute bronchiolitis is a common illness accounting for $500 million annually in hospitalizations. Despite the frequency of bronchiolitis, its diagnosis and management is variable. To address this variability, the American Academy of Pediatrics (AAP) published an evidence‐based practice management guideline for bronchiolitis in 2006.