Month: January 2020

In this paper, we adopted a mixed sampling strategy to obtain the transcriptional profile of three vegetative tissues of the paper mulberry. About 54,638,676 Illumina reads were de novo assembled for the first time to build the transcriptome of the paper mulberry. Sequence information for those genes involved in the biosynthesis of flavonoids, cellulose and other compound can be used for metabolic engineering of the paper mulberry. The large number of transcripts reported in the current study additionally serves as an invaluable genetic resource for crop improvement of paper mulberry as well as other plants. Despite the important economic value of the paper mulberry, its transcriptomic and genomic data are not available in public databases. Illumina RNA-seq technology has been extensively used in the transcriptome sequencing for the model plants with reference genome data or non-model plants without reference genomic information. Here, we obtained for the first time the genome-wide expression profiling of the paper mulberry using the Illumina sequencing platform and the Trinity program. The bidirectional interaction between depression and ischemic heart disease has been documented numerous times and is generally accepted. After an acute myocardial infarction the risk of being depressed is approximately 3 times increased as compared with the general population. In out-patients the 12month odds ratio of major depression has been found to be 2.3 times higher in individuals with cardiac disease as compared with those with no medical illness. In initially healthy people clinical depression as well as depressive mood is associated with a significantly increased risk of developing IHD. Further, depression after a MI doubles both the risk of a cardiac re-event during the first years post MI, as well the risk of 2 years mortality. Depression, quality of life and general well-being is all part of the chronic stress concept. Stress is vaguely defined but is generally accepted as a risk factor for a poor outcome in IHD. Chronic stress is associated with cardiovascular re-events and death from IHD and patients with MI have been shown to have higher stress levels when measured both as stress at work, stress at home, financial stress and major life-event stress. Chronic stress and depression is associated with widespread increased pain sensitivity, leading to both hyperalgesia and allodynia. The increase in pain sensitivity might be due to the neuroplastic effects of chronic stress on pain circuitry i.e. the diffuse noxious inhibitory control system. DNIC is an endogenous pathway mediating inhibition of lamina I neurons in the spinal dorsal root when pain signals ascend from the periphery through sensory C fiber neurons distributed wide spread over the body in the epidermis and up through the spinal cord. Patients with hypersensitivity to pain have been shown to have an impaired DNIC modulation.

Furthermore, low responders to clopidogrel because of a CYP2C19 polymorphism. However, easy, fast, and low-cost laboratory examinations to monitor the effect of APA on an individual patient’s platelets are not readily available. For some patients, a certain dose may not be sufficient to prevent thrombotic events, while for others, that same dose might cause dangerous bleeding complications such as ICH. For low responders to APA, in whom platelet function and coagulation parameters are normal, even when given concomitantly with APA, PLT might induce overcoagulation around the ICH site. Taking drug resistance into consideration, clarification of the effects of PLT on ICH prognosis will require a prospective cohort study with monitoring of the effects of APA. A key limitation in this study was the short duration of observation, because patients were often moved to other institutions within a short period of time following admission, due to limited capacity at our hospital. In addition, we need an increased sample size to evaluate better the PLT effect in the multivariate regression analysis. Another disadvantage in this study was that the decision to give a PLT depended on the resident neurosurgeon. However, the strength of our study was that this was the first to look at the effect of PLT in a population of Asian patients with ICH plus concomitant APA; all three previous studies have dealt mainly with Caucasian patients. As Asian people tend to be APA resistant, PLT seemed to be less necessary compared with Caucasians even in cases of ICH with APA. Finally, as this was a single-institution study, our patients were evaluated using consistent methods and procedures. To evaluate the true effects of PLT on ICH survival, animal models and prospective stratified cohorts taking into account the effects of APAs are necessary. Various beneficial or probiotic effects have been attributed to strains belonging to the genera Bifidobacterium and Lactobacillus. Probiotic bacteria have been used to treat, among others, antibiotic-associated diarrhea, food allergies, atopic eczema, inflammatory bowel disease and arthritis. In addition, several studies have inferred a role for probiotic bacteria as antagonists of pathogenic bacteria. Proposed mechanisms of action include competition for the same attachment sites as pathogenic bacteria, competition for nutrients, production of growth-inhibitory compounds and stimulation of the immune system. Whether probiotics need to adhere to epithelial cells of the human gut in order to exert their beneficial effect is still a matter of debate, but close contact between the two is required at some stage. Bacterial adhesion to the gut epithelium is a complex process in which host, bacterial and environmental factors interact, and it is reasoned that adhesion and associated probiotic activities are regulated by bacterial cell-to-cell communication systems.

Thus, the in vivo roles of endogenous cathelicidin in host defence against P. aeruginosa, the relative effects of microbicidal and modulatory properties, and the consequences of therapeutic targeting of cathelicidin expression or exogenous delivery of peptide remain unknown. We demonstrate that therapeutically administered synthetic LL37 peptide can enhance the clearance of P. aeruginosa from the murine lung, in the absence of demonstrable direct microbicidal effects, and can induce an upregulation of the early neutrophil response to pathogen in the lungs that is dependent both upon the presence of the peptide and the pathogen. We show that despite a normal early neutrophil response, second phase pulmonary neutrophil influx was deficient in Camp2/2 mice, with impaired clearance of pulmonary P. aeruginosa. Delivery of LL-37 to these cathelicidin-deficient mice enhanced the neutrophil response and restore bacterial clearance, demonstrating proof of principle for therapeutic use of LL-37 in cathelicidin deficiency. These studies indicate that the protective effects of cathelicidins in P. aeruginosa infection in vivo can result from modulatory effects in innate immune responses, synergising with infectious stimuli to enhance a protective neutrophil response. Cathelicidins are recognised as key multifunctional modulators of innate immunity and host defence against infection, and offer possible novel therapeutic templates. In addition to directly microbicidal potential, these peptides have been described as having a broad range of inflammomodulatory and immunomod ulatory properties. However, no clear evidence exists for these functions being involved in cathelicidin-mediated enhanced host defence against pulmonary infection in vivo, with the relative significance of microbicidal potential and modulatory functions remaining unclear. Using a murine model of acute P. aeruginosa lung infection, we demonstrate cathelicidin-mediated enhancement of bacterial clearance in vivo in the absence of direct early microbicidal activity. Administration of synthetic LL-37 promoted an upregulation of the early neutrophil response that was dependent upon both infection and peptide, but was independent of native cathelicidin production, and enhanced bacterial clearance from the lung. The associations between hCAP-18/LL-37 expression and susceptibility to infection in humans suggest an important, but as yet undefined role for hCAP-18/LL-37 in innate host defence against infection in humans. Although this peptide has microbicidal potential, its activity is poor against many microorganisms in physiologically relevant environments at the low concentrations found in vivo in most systems. However, cathelicidins have additionally been shown to have multiple modulatory activities, including chemotactic function, the ability to modulate chemokine, cytokine and cellular responses.

Which are observed in both animal models as well as human infant studies. Furthermore, the fact that hyperoxia exposure led to a decrease in VEGF-A, a critical factor for angiogenesis, concurs with the current understanding that this protein is critical for normal alveoli development. Our finding of a significant decrease in TGFb2 with hyperoxia exposure as well as the other signaling proteins important in the TGF-BMP-Smad pathway is in contrast to some studies of neonatal hyperoxia-induced lung injury where an elevation of TGF-b isoforms are seen with hyperoxia exposure. There are a couple of possible explanations for this discrepancy. First, many studies measured only TGFb1, the predominant isoform, and although we saw a lowering in gene expression with hyperoxia, it was not statistically different from the control or normoxia group. Our hyperoxia model is of 10-day duration and longer durations of hyperoxia exposure may be needed to see a change in TGFb1. It is possible that there is a biphasic change in TGFb isoforms similar to VEGF where a decrease is observed early in the course of disease evolution and this is followed by a later increase. Little data exists to the timing and changes seen in TGFb2 gene expression with hyperoxia and its specific role in lung development. However, our finding of decreased expression of TGFb2 and Smad 3 with hyperoxia and concomitantly alveolar simplification and, in contrast, an increase in TGFb2 and Smad 3 in the LXA4 and combination groups with parallel improved alveolarization is consistent with scientific literature examining the complex role of TGFb isoforms in lung development. This duality of TGFb function in lung development under different conditions is supported by Vincencio et al. demonstrating that TGFb can induce changes of BPD when over expressed between postnatal days P7 and P14 in a murine model. Yet in contrast, knockout mouse models of Smad3 overlapping with this time period indicate that the TGFb/Smad3 signaling pathway can beneficially induce alveolarization. Thus the timing of the change in TGFb and Smad3 expression relative to the period in lung development may be the defining factor as to whether it inhibits or promotes airway maturation. However, although some aspects may be shared in the pathophysiology of adult and neonatal lung injury, the neonate, especially the preterm infant, is unique in that lung development is still ongoing and the compromise in normal developmental processes also contributes to the specific features in neonatal lung injury. Our date indicate that RvD1 impacted the expression of genes for both inflammation and the extracellular matrix biomarker, both of which may have contributed to reducing septal wall thickness. RvD1 did not have a substantial effect alone on VEGF-A or the other growth factor biomarkers in the TGFb family. Nor did RvD1 impact the expression of the BMP-Smad signaling proteins.

They are organized in five parallel cortico-basal ganglia-thalamocortical circuits, including the sensorimotor, associative and limbic circuits. GP and STN are the two principal components of the indirect pathway in these circuits, with the STN considered as a driving force of the output structures of basal ganglia. Based on our recent data, it is likely that the changes recorded in GP after Mn intoxication are a consequence of 5-HT depletion, but not NE depletion. Indeed, selective depletion of 5-HT by pCPA administration resulted in the same decrease of the firing rate and increase in the proportion of irregular and bursty neurons in GP. However, DSP-4, which is selective for NE depletion did not alter by itself the firing rate or the pattern of GP neurons. Interestingly, and in contrast to GP, the changes observed in STN neurons after repeated Mn intoxication are likely to be due to NE depletion, but not to 5-HT depletion. Indeed, DSP-4 administration resulted in the same decrease of the firing rate and increase in the proportion of irregular neurons recorded in the STN. However, selective 5-HT depletion did not alter the firing rate nor the pattern of STN neurons. Besides, lead intoxication, which reduced the tissue contents of NE without affecting the 5-HT system, changed in a similar way the firing activity of STN neurons. In addition to the depletion of NE and 5-HT, we cannot exclude that the changes in the firing activity of GP and STN neurons can also be due to the accumulation of Mn in GP and STN. Neuroimaging studies have shown an accumulation of Mn in the basal ganglia in addition to the frontal and parietal cortex. From a pathophysiological point of view, the firing activity changes of GP neurons after Mn intoxication is nearly similar to those observed in the 6-OHDA rat model of Parkinson’s disease, although the origin is not the same. However, the changes in STN neuronal activity in Mn-intoxicated animals are different from those observed after 6-OHDA-induced DA depletion in the striatum. While 6-OHDA lesion induced a switch from regular to bursty pattern with oscillations, Mn intoxication induced a switch from regular to irregular pattern. Together, these findings provide a logical explanation to the evidence that Mn-induced motor and nonmotor deficits are not improved by L-Dopa therapy as it does in Parkinson’s disease. In conclusion, the present study provides evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism. Iron is required at the active center of several important enzymes, including those involved in the tricarboxylic acid cycle, respiration, lipid metabolism, DNA replication and repair. Because of its ability to lose or gain a single electron.