Dendritic Cell Cross-Priming Is Essential for Immune Responses to Listeria monocytogenes

Cross-presentation is now recognized as a major mechanism for initiating CD8 T cell responses to virus and tumor antigens in vivo. It provides an elegant mechanism that allows relatively few Dendritic cells (DCs) to initiate primary immune responses while avoiding the consumptive nature of pathogenic infection. CD8 T cells play a major role in anti-bacterial immune responses; however, the contribution of cross-presentation for priming CD8 T cell responses to bacteria, in vivo, is not well established. Listeria monocytogenes (Listeria) is the causative agent of Listeriosis, an opportunistic food-borne bacterial infection that poses a significant public health risk. Here, we employ a transgenic mouse model in which cross-presentation is uniquely inactivated, to investigate cross-priming during primary Listeria infection. We show that cross-priming deficient mice are severely compromised in their ability to generate antigen-specific T cells to stimulate MHC I-restricted CTL responses following Listeria infection. The defect in generation of Listeria-elicited CD8 T cell responses is also apparent in vitro. However, in this setting, the endogenous route of processing Listeria-derived antigens is predominant. This reveals a new experimental dichotomy whereby functional sampling of Listeria-derived antigens in vivo but not in vitro is dependent on cross-presentation of exogenously derived antigen. Thus, under normal physiological circumstances, cross-presentation is demonstrated to play an essential role in priming CD8 T cell responses to bacteria

Apparent stress-strain relationships in experimental equipment where magnetorheological fluids operate under compression mode

Abstract: This paper presents an experimental investigation of two different magnetorheological ( MR) fluids, namely, water-based and hydrocarbon-based MR fluids in compression mode under various applied currents. Finite element method magnetics was used to predict the magnetic field distribution inside the MR fluids generated by a coil. A test rig was constructed where the MR fluid was sandwiched between two flat surfaces. During the compression, the upper surface was moved towards the lower surface in a vertical direction. Stress-strain relationships were obtained for arrangements of equipment where each type of fluid was involved, using compression test equipment. The apparent compressive stress was found to be increased with the increase in magnetic field strength. In addition, the apparent compressive stress of the water-based MR fluid showed a response to the compressive strain of greater magnitude. However, during the compression process, the hydrocarbon-based MR fluid appeared to show a unique behaviour where an abrupt pressure drop was discovered in a region where the apparent compressive stress would be expected to increase steadily. The conclusion is drawn that the apparent compressive stress of MR fluids is influenced strongly by the nature of the carrier fluid and by the magnitude of the applied current

Impact of b-value on estimates of apparent fibre density

Recent advances in diffusion magnetic resonance imaging (dMRI) analysis techniques have improved our understanding of fibre-specific variations in white matter microstructure. Increasingly, studies are adopting multi-shell dMRI acquisitions to improve the robustness of dMRI-based inferences. However, the impact of b-value choice on the estimation of dMRI measures such as apparent fibre density (AFD) derived from spherical deconvolution is not known. Here, we investigate the impact of b-value sampling scheme on estimates of AFD. First, we performed simulations to assess the correspondence between AFD and simulated intra-axonal signal fraction across multiple b-value sampling schemes. We then studied the impact of sampling scheme on the relationship between AFD and age in a developmental population (n=78) aged 8-18 (mean=12.4, SD=2.9 years) using hierarchical clustering and whole brain fixel-based analyses. Multi-shell dMRI data were collected at 3.0T using ultra-strong gradients (300 mT/m), using 6 diffusion-weighted shells ranging from 0 – 6000 s/mm2. Simulations revealed that the correspondence between estimated AFD and simulated intra-axonal signal fraction was improved with high b-value shells due to increased suppression of the extra-axonal signal. These results were supported by in vivo data, as sensitivity to developmental age-relationships was improved with increasing b-value (b=6000 s/mm2, median R2 = .34; b=4000 s/mm2, median R2 = .29; b=2400 s/mm2, median R2 = .21; b=1200 s/mm2, median R2 = .17) in a tract-specific fashion. Overall, estimates of AFD and age-related microstructural development were better characterised at high diffusion-weightings due to improved correspondence with intra-axonal properties

Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience

Trust and childhood maltreatment: evidence of bias in appraisal of unfamiliar faces

Background: Child maltreatment is associated with poorer social functioning and increased risk of mental health problems in adolescence and adulthood, but the processes underlying these associations remain unclear. Although crucial for establishing and maintaining relationships, trust judgements have not been experimentally investigated in children who have experienced abuse and neglect. Methods: A community-based sample of 75 children aged 8– 16 years with maltreatment documented on the basis of social services records, and a group of 70 peers matched on age, gender, cognitive ability, socioeconomic status, and ethnicity took part in the study. Children completed a trustworthiness face-judgement task in which they appraised the trustworthiness of unfamiliar facial stimuli varying along a computationally modelled trustworthiness dimension. Results: In line with clinical observations that childhood maltreatment is associated with an atypical pattern of trust processing, children with maltreatment experience were significantly less likely than their peers to rate unfamiliar faces as trustworthy. Moreover, they were more variable in their trust attributions than their peers. Conclusions: The study provides compelling experimental evidence that children with documented maltreatment perceive others as less trustworthy than their peers and are less consistent in their estimates of trustworthiness in others. Over time, alterations in trust processing may disrupt the development of social bonds and contribute to ‘social thinning’ (a reduction in the extent and quality of social relationships), leaving children more vulnerable to environmental stressors, increasing risk of mental health difficulties

Durability and Microstructure of Cement Composites Containing Qatar's Municipal Wastes

Qatar produces more than 2.5 million tons of municipal waste per year with an average waste generation rate of 1.8 kg/day/capita which is one of the highest rates in the world. The rapid growth of municipal solid waste has become one of the serious environmental problem that Qatar is facing with. Qatar's municipal waste is composed of organic and recyclables materials. Municipal solid waste incineration has been performed in Qatar since 2011. By incineration of wastes, not only the volume and weight of wastes are reduced but also energy is generated. Prior to incineration of municipal wastes, recyclables are separated from the waste and the remaining waste is incinerated at a minimum temperature of 850oC. Bottom ash and fly ash are produced as a result of incineration process. These by-products may contain heavy metals and pose a thread to the environment hence needs treatment and/or special disposal. Approximately 60 tonnes of fly ash is generated daily from municipal waste incineration in Qatar and this ash called as municipal solid waste incineration (MSWI) fly ash. This MSWI fly ash is stabilised with cement and then disposed into special landfill. However, cementitious property of MSWI fly ash due to similar mineralogical composition with cement and its finer particle size may favor its potential utilisation in cement based materials. As aforementioned before, 40% of municipal waste of Qatar is composed of recyclables of which 14% is plastic. The major portion of plastic wastes, about 90% of total, are composed of light density polyethylene (LDPE) and high density polyethylene (HDPE) wastes. Therefore, there is a huge potential for recycling of PE wastes in Qatar considering the shortage of raw materials i.e. natural aggregate for construction industry. The scarcity of available land for disposal of municipal wastes and limited natural resources of raw materials for construction industry has opened new research areas for proper disposal and recycling of municipal wastes. Therefore, in this research work, municipal solid waste incineration (MSWI) fly ash and municipal polymeric wastes were used as secondary raw materials for the preparation of cement based composites. MSWI fly ash was utilised as partial replacement of cement by 10% by weight. Polyetyhlene wastes in granular form were utilised as partial replacement of natural aggregate by 10% by volume. Portland cement, silica fume (10% by weight) and MSWI FA (10% by weight) at constant rates were used as binder in all cement-based composites. Three different cement based composites were fabricated by partial substition of natural aggregate with LDPE and HDPE wastes at 0 and 10% by volume. The mixture without PE waste substitution was called as the reference mixture, with LDPE waste was called as Mix 1 and with HDPE waste was called as Mix 2. Besides mechanical performance, durability of fabricated cement composites containing municipal wastes was investigated to determine if their utilisation has positive contribution or adverse impact. The durability properties were examined by performing drying shrinkage and expansion under sulfate exposure tests. Scanning electron microscopy coupled with EDX were used to determine the degradation products of sulfate exposure. In terms of mechanical strength, samples containing PE wastes showed lower strength at early ages due to weaker bonding between LDPE/HDPE and the cement matrix. At later ages, strength improvement was observed and comparable strength values for Mix 1 and Mix 2 were measured with respect to the reference. The effect of utilisation of municipal wastes on the dimensional stability of cement composites was evaluated by measuring the variation of length change at 4, 11, 18, 25, 126 and 168 days of air drying. This test showed that incorporation of PE wastes (Mix 1 and Mix 2) reduced the drying shrinkage and provided better dimensional stability compared to the reference. Sulfate attack is known as one of the most deleterious effects on cement based composites due to the formation of expansive degradation products. To investigate the sulfate resistance of fabricated composites, the length change at 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, 13 weeks, 15 weeks, 4 months and 6 months of sulfate exposure was measured. Both the reference and samples containing PE wastes did not show any visual deterioration except a white and soft layer formed on top of all samples. The length change indicated that composites containing PE wastes experienced reduction in expansion compared to the reference and hence considered as more durable for external sulfate attack. More voids and pores were present in PE incorporated samples, therefore sulfate degradation products probably filled these pores and resulted in lower expansion compared to the reference. There was no significant difference between the mechanical performance and durability of cement composites containing LDPE and HDPE. The microstructure and composition of sulfate degradation products were investigated by SEM-EDX. The decalcification of the C-S-H phase were detected in each sample. Gypsum, calcite and thaumasite were identified as the major deterioration related products, while ettringite was found at trace level. This laboratory study showed that MSWI fly ash and PE wastes can be utilised together to produce durable cement based materials with a lower carbon footprint.qscienc

Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in non-hematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects

The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study

Background We recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden. Methods Following the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains. Results Questionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1–3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types. Conclusions Headache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania

Существует ли связь между средним уровнем mIDkIne и прогнозом заболевания COVID-19?

   The objective was aimed to measure plasma midkine (MK)* levels in patients with COVID-19 and assess its clinical significance.   Materials and Methods. 88 patients observed in our hospital with a diagnosis of COVID-19 were included in the study. The patients’ demographic characteristics, clinical, and laboratory data were studied, and the relationship between MK levels, prognosis, and other parameters was investigated.   Results. Of the 88 patients included in the study, 43 (48.9 %) were female and 45 (51.1%) were male. 24 (27%) patients died. The mean age of non-survivors was 70 ± 12.3 years and the survivors were 61.9 ± 18.2 years. Mortality predictors such as D-dimer, ferritin, troponin, LDH, CRP, and procalcitonin were significantly higher in non-survivors than in survivors (p &lt; 0.05). The median MK level (IR) was 152.5 ± 125 pg/ml in all patients, 143 ± 149 pg/ml in survivors, and 165.5 ± 76 pg/ml in non-survivors (p = 0.546). The difference between these two groups was not statistically significant. The area under the ROC curve was found to be 0.542 (95% CI 0.423–0.661, p = 0.546).   Conclusion. MK is not a biomarker that can replace or reinforce known predictors of mortality in COVID-19 patients.   Цель. Исследование направлено на измерение уровня Midkine (MK)* в плазме крови у пациентов с COVID-19 и оценку его клинической значимости.   Материалы и методы. В исследование включены 88 пациентов, наблюдавшихся в клинике с диагнозом COVID-19. Изучены демографические характеристики пациентов, клинические и лабораторные данные, а также исследована взаимосвязь между уровнями MK, прогнозом и другими параметрами.   Результаты. Из 88 пациентов, включенных в исследование, 43 (48,9 %) были женщинами и 45 (51,1 %) – мужчинами. 24 (27 %) пациента умерли. Средний возраст невыживших составил 70 ± 12,3 года, а выживших – 61,9 ± 18,2 года. Предикторы смертности, такие как D-димер, ферритин, тропонин, ЛДГ, СРБ и прокальцитонин, были значительно выше у умерших, чем у выживших (р &lt; 0,05). Медиана уровня МК (IR) составила 152,5 ± 125 пг/мл у всех пациентов, 143 ± 149 пг/мл у выживших и 165,5 ± 76 пг/мл у умерших (р = 0,546). Разница между этими 2 группами была незначима. Было обнаружено, что площадь под кривой ROC составляет 0,542 (95 % ДИ 0,423–0,661, р = 0,546).   Вывод. МК не является биомаркером, который может заменить или усилить известные предикторы смертности у пациентов с COVID-19