Genetic factors regulating lung vasculature and immune cell functions associate with resistance to pneumococcal infection

Streptococcus pneumoniae is an important human pathogen responsible for high mortality and morbidity worldwide. The susceptibility to pneumococcal infections is controlled by as yet unknown genetic factors. To elucidate these factors could help to develop new medical treatments and tools to identify those most at risk. In recent years genome wide association studies (GWAS) in mice and humans have proved successful in identification of causal genes involved in many complex diseases for example diabetes, systemic lupus or cholesterol metabolism. In this study a GWAS approach was used to map genetic loci associated with susceptibility to pneumococcal infection in 26 inbred mouse strains. As a result four candidate QTLs were identified on chromosomes 7, 13, 18 and 19. Interestingly, the QTL on chromosome 7 was located within S. pneumoniae resistance QTL (Spir1) identified previously in a linkage study of BALB/cOlaHsd and CBA/CaOlaHsd F2 intercrosses. We showed that only a limited number of genes encoded within the QTLs carried phenotype-associated polymorphisms (22 genes out of several hundred located within the QTLs). These candidate genes are known to regulate TGFb signalling, smooth muscle and immune cells functions. Interestingly, our pulmonary histopathology and gene expression data demonstrated, lung vasculature plays an important role in resistance to pneumococcal infection. Therefore we concluded that the cumulative effect of these candidate genes on vasculature and immune cells functions as contributory factors in the observed differences in susceptibility to pneumococcal infection. We also propose that TGFbmediated regulation of fibroblast differentiation plays an important role in development of invasive pneumococcal disease.This work was supported by the European Union-funded Pneumopath Project HEALTH-F3-2009-222983. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer-reviewedPublisher Versio

Postural stability analysis with inertial measurement units in alzheimer’s disease

BACKGROUND: The cause of frequent falls in patients with Alzheimer's disease (AD) is still not well understood. Nevertheless, balance control and sensory organization are known to be critical for moving safely and adapting to the environment. METHODS: We evaluated postural stability in 20 AD patients (11 fallers and 9 nonfallers) and 16 healthy controls with an inertial measurement unit (triaxial accelerometers and gyroscopes) attached to the center of mass (COM) in different balance conditions (Romberg on flat surface and frontward/backward-inclined surface, with or without visual suppression) in a motor lab. RESULTS: In AD patients, the group of fallers showed a different kinetic pattern of postural stability characterized by higher vulnerability to visual suppression, higher total/maximal displacement and a mediolateral/anteroposterior range of sway, and a consequent need for more corrections of COM pitch and roll angles. CONCLUSION: Further studies are needed to consolidate the normative values of the discriminatory kinetic variables with the potential of inclusion in a multifactorial analysis of the risk of falls. Nevertheless, these results highlight signs of impairment of central postural control in AD, which may require early therapeutic intervention.The Center ALGORITMI was funded by the Neural Engineering Transformative Technologies (NETT) project

Acute exposure of mice to high-dose ultrafine carbon black decreases susceptibility to pneumococcal pneumonia

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies suggest that inhalation of carbonaceous particulate matter from biomass combustion increases susceptibility to bacterial pneumonia. <it>In vitro </it>studies report that phagocytosis of carbon black by alveolar macrophages (AM) impairs killing of <it>Streptococcus pneumoniae</it>. We have previously reported high levels of black carbon in AM from biomass smoke-exposed children and adults. We therefore aimed to use a mouse model to test the hypothesis that high levels of carbon loading of AM <it>in vivo </it>increases susceptibility to pneumococcal pneumonia.</p> <p>Methods</p> <p>Female outbred mice were treated with either intranasal phosphate buffered saline (PBS) or ultrafine carbon black (UF-CB in PBS; 500 μg on day 1 and day 4), and then infected with <it>S. pneumoniae </it>strain D39 on day 5. Survival was assessed over 72 h. The effect of UF-CB on AM carbon loading, airway inflammation, and a urinary marker of pulmonary oxidative stress was assessed in uninfected animals.</p> <p>Results</p> <p>Instillation of UF-CB in mice resulted a pattern of AM carbon loading similar to that of biomass-smoke exposed humans. In uninfected animals, UF-CB treated animals had increased urinary 8-oxodG (P = 0.055), and an increased airway neutrophil differential count (P < 0.01). All PBS-treated mice died within 72 h after infection with S<it>. pneumoniae</it>, whereas morbidity and mortality after infection was reduced in UF-CB treated animals (median survival 48 h vs. 30 h, P < 0.001). At 24 hr post-infection, UF-CB treated mice had lower lung and the blood S<it>. pneumoniae </it>colony forming unit counts, and lower airway levels of keratinocyte-derived chemokine/growth-related oncogene (KC/GRO), and interferon gamma.</p> <p>Conclusion</p> <p>Acute high level loading of AM with ultrafine carbon black particles <it>per se </it>does not increase the susceptibility of mice to pneumococcal infection <it>in vivo</it>.</p

The effect of levodopa on postural stability evaluated by wearable inertial measurement units for idiopathic and vascular Parkinson’s disease

BACKGROUND: Postural stability analysis has shown that postural control is impaired in untreated idiopathic Parkinson's disease (IPD), even in the early stages of the disease. Vascular Parkinson's disease (VPD) lacks consensus clinical criteria or diagnostic tests. Moreover, the levodopa effect on postural balance remains undefined for IPD and even less so for VPD. OBJECTIVE: To characterize postural stability, using kinematic analysis with wearable inertial measurement units, in IPD and VPD patients without clinical PI, and to subsequently analyze the response to levodopa. METHODS: Ten patients with akinetic-rigid IPD and five patients with VPD were included. Clinical and postural stability kinematic analysis was performed before and after levodopa challenge, on different standing tasks: normal stance (NS), Romberg eyes open (REO) and Romberg eyes closed. RESULTS: In the "off state", VPD patients had higher mean distances and higher maximal distance of postural sway on NS and REO tasks, respectively. VPD patients maintained a higher range of anterior-posterior (AP) postural sway after levodopa. In the absence of PI and non-significant differences in UPDRS-III, a higher mPIGD score in the VPD patients was mainly due to gait disturbance. Gait disturbance, and not UPDRS-III, influenced the degree of postural sway response to levodopa for VPD patients. CONCLUSION: Quantitative postural sway evaluation is useful in the investigation of Parkinsonian syndromes. VPD patients have higher AP postural sway that is correlated with their gait disturbance burden and also not responsive to levodopa. These observations corroborate the interconnection of postural control and locomotor networks

Hydrogen production from sodium borohydride on a Ni-Ru catalyst : an electrochemical study

Previous work by the authors has demonstrated a high rate and high yield hydrolysis of sodium borohydride, in the presence of a Ni-Ru catalyst synthesized by wet chemistry. The catalyst has been fully characterized and utilized more than 300 times exhibiting high stability and durability. In this work, results of an electrochemical study are reported using the powder catalyst supported on a Ni foam in order to measure the open circuit potential during hydrogen production and to study the reaction using voltammetry and ac impedance. Production rates were as high as 10 Lmin-1gcat -1 at 65ºC. Electrochemical studies indicated that the hydrogen evolution mechanism corresponds to a Volmer- Heyrovsky type, suggested by a Tafel slope of 117 mVdec-1. Tafel region potentials are in agreement with values found for hydrolysis at the open circuit. The Langmuir-Hinshelwood mechanism explains the hydrolysis of sodium borohydride using a Ni-Ru catalyst. The role of Ni and Ru is briefly discussed

Оголені душі

Рецензія на книги: Слапчук Василь. Осiнь за щокою: Роман. - К.: Факт, 2006. - 280 с. та Сорока Петро. Денники 2004 - 2005. - Тернопiль: Сорока, 2006. - 364 с

Pt-Ru Catalysts supported on mesoporous carbons for polymer electrolyte membrane fuel cells

Pt-Ru electrocatalysts supported on xerogels and CMK-3 ordered mesoporous carbons were synthesized by reduction with formate ions (SFM method). Some of the carbon supports were chemically treated with HNO3 in order to generate oxygen groups on the surface, while other supports were heat treated. Physical characterization of the catalyst was obtained using X-ray dispersive energy (EDX) and X-ray diffraction (XRD) techniques. Results showed that Pt-Ru catalysts with similar metal content (20%) and atomic ratios (Pt:Ru 1:1) were obtained. The electrochemical activity was studied by cyclic voltammetry and chronoamperometry. Higher methanol oxidation current densities were found for catalyst deposited on chemically treated supports. Electrode preparation and MEA assembly allowed an in-house built direct methanol fuel to be fitted with the synthesized catalysts and supports in order to assess their performance. Cell and reactants were conditioned by a direct methanol test station. Polarisation curves were measured and confirmed data obtained by voltammetry, regarding the effect of heat treatment of the carbon support. Normalised power curves per weight of catalyst are discussed in terms of the significant impact on noble metal loading and attained cell maximum power, in comparison with results obtained with a commercial catalyst

Influence of catalyst support characteristics and functionalization on the catalytic activity of Pt-Ru for PEM fuel cells

Pt-Ru electrocatalysts supported on carbon xerogels and ordered mesoporous carbons were synthesized by reduction with formate ions (SFM method). Chemical and heat treatments were applied to modified the surface chemistry of original carbon supports. Physical characterization of the catalysts was performed using X-ray dispersive energy (EDX) and X-ray diffraction (XRD) techniques, while the electrochemical activity towards methanol oxidation was studied by cyclic voltammetry (CV). Pt-Ru catalysts with nominal metal content (20 wt.%) and atomic ratios (Pt:Ru 1:1) were successfully synthesized on the different supports. Higher methanol oxidation current densities were obtained for those supports with a higher content of surface oxygen groups. Gas diffusion electrode and membrane-electrode-assembly preparation allowed an in-house built of a direct methanol fuel monocell for the evaluation of the catalysts performance. Polarization curves were measured confirming the results obtained in a three electrodes electrochemical cell by CV. Normalized power curves per weight of Pt are discussed in terms of the significant impact on noble metal loading and attained cell maximum power, in comparison with results obtained with a commercial catalyst

The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection

Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.info:eu-repo/semantics/publishedVersio