In this study we verified the causal role of the bilateral dorsolateral prefrontal cortex (DLPFC) in emotional regulation using a strategy of reappraisal, which involves intentionally changing the ...meaning of an affective event to reduce its emotional impact. Healthy participants (n = 26; mean age = 25.4) underwent three sessions of inhibitory continuous theta burst stimulation (cTBS) applied on three different days over the left or right DLPFC, or the vertex. After applying the stimulation protocol participants were presented with neutral and negative pictorial stimuli that had to be either passively watched or reappraised. The efficacy of emotional control was quantified using the Late Positive Potential (LPP), the neural marker of motivated attention and elaborated stimulus processing. The results showed that reappraisal was compromised after inhibitory stimulation of the right DLPFC compared to the vertex. This impairment of affective modulation was reflected in both early (350-750 ms) and late (750-1500 ms) time windows. As no session differences during the passive watching conditions were found, the decrease in reappraisal efficacy due to non-specific changes in basic perceptual processing was considered unlikely. Instead, we suggest that inhibition of the right DLPFC primarily affects the top-down mechanism of attentional deployment. This results in disturbances of attentional processes that are necessary to thoroughly elaborate the content of affective stimuli to enable their new, less negative interpretation.
Taking into account functional traits in the breeding practice should lead to a longer productive life of cows. However, despite the increased contribution of these traits in bull selection indices, ...their daughters are frequently culled as early as the 2nd or 3rd lactation. The problem is whether and to what extent the genetic potential of animals is realized in the production practice. Therefore, the purpose of this study was to determine the associations between the breeding value (BV) of bulls and their daughters for cow longevity and culling reasons in the Holstein-Friesian cattle population in Poland. Data for 532 062 cows culled in 2012, 2015, and 2018 were analyzed. A majority of 5 045 cow sires originated from Poland, Germany, France, the Netherlands, and the United States. The highest variation in the contribution of culling reasons was for the cows culled at the age of 2–4 years. The contribution of the culling reasons, analyzed in relation to the cow culling age, remained similar and the only exception was culling because of old age, for which a significant increase was observed only for the culling age of at least 9 years (13.8%), which was reached by only 7.3% of the cows. The sires were characterized by generally high BV for conformation and reproductive traits. However, they had, at most, the average genetic potential for functional longevity. There were a number of beneficial associations found between the BV of bulls and the distribution of culling reasons in their daughters. For example, it concerns relations between the somatic cell score in milk and culling due to udder diseases and low milk yield, between the interval from calving to first insemination and low milk yield, between the protein yield and old age, or between the BV for certain conformation traits (size, udder) and cow culling due to age. In these cases, as the BV increased for a given trait, the contribution of the corresponding cow culling reason tended to decrease. Our study showed that it seems reasonable to consider Holstein-Friesian cows aged at least 9 years at culling to be long-living animals. This is primarily evidenced by the rapid increase in the culling due to old age in relation to younger cows. Nowadays the above age limit can be suggested as a criterion of longevity for Holstein-Friesian cows but the criterion should be updated to the relation genotype-environment-economy that tends to change over time.
Cow longevity and lifetime performance traits are good indicators of breeding effectiveness and animal welfare. They are also interrelated with the economics of dairy herd. Unfortunately, a high milk ...yield is often associated with deteriorated cow health and fertility and, consequently, with an increased culling rate. This situation, observed also in the Polish population of Holstein-Friesian cattle, inspired us to undertake a study on the associations between some factors and lifetime performance characteristics. The data set consisted of the records on 135 496 cows, including 131 526 of the Black and White strain (BW), and 3970 of the Red and White strain (RW) covered by performance recording and culled in 2012. It was found that cows of the BW strain and those from the largest herds (>100 cows) reached higher lifetime and mean daily energy-corrected milk (ECM) yields than cows of the RW strain and those from smaller herds culled at a similar age. Cows youngest at first calving (<2.0 years) were characterised by the highest lifetime ECM yield. It indicates that heifers can be bred even when they are younger than 15 to 16 months with no significant negative effect on their later performance. Infertility and reproduction problems (39.6%) and udder diseases (15.5%) constituted the most frequent reasons for cow culling. Cow longevity and lifetime productivity were considerably affected by the interactions between the studied factors.
Summary
Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released ...during traps formation. We measured circulating cell‐free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real‐time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.
In the forward end-cap of the Belle II spectrometer, particle identification is provided by a proximity focusing RICH detector with an aerogel radiator (ARICH). The ARICH’s primary function is to ...effectively distinguish between pions and kaons in the momentum range of 0.5GeV/c to about 4GeV/c, as well as to contribute to identification of low-momentum leptons. Since its operation began, Belle II has collected over 420fb−1 of data. Based on this large data sample, studies of several effects that impact the performance of the ARICH detector were carried out. In this paper, we present a comparison of the observed Cherenkov ring image and detector particle identification performance in the measured data and detector simulation. Furthermore, we highlight recent efforts aimed at enhancing the ARICH’s performance by taking into account the effects of particle decay in flight and scattering in materials before the detector, as well as by refining the probability density function used for particle identification likelihood evaluation.
Objectives: Neutrophil apoptosis is mandatory for resolving inflammation and is regulated by expression of pro- and anti-apoptotic genes. We studied neutrophils isolated from patients with ...granulomatosis with polyangiitis (GPA) to investigate apoptosis alterations and to identify transcriptional and circulating factors affecting this process.
Method: We enrolled 36 patients (18 in active stage, 18 in remission) and 18 healthy controls. Circulating levels of tumour necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage migration inhibitory factor, plasminogen activator inhibitor-1, interferon-γ, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule-1, soluble Fas (sFas), sFas ligand, survivin, and pentraxin-3 (PTX3) were evaluated by enzyme-linked immunosorbent assay/Luminex; circulating apoptotic neutrophils by flow cytometry; and apoptosis-related gene transcripts by real-time polymerase chain reaction.
Results: Patients had decreased fractions of circulating apoptotic neutrophils and delayed neutrophil apoptosis was present in vitro. Circulating levels of TNF-α, GM-CSF, sFas, and PTX3 were higher in GPA. Delayed neutrophil apoptosis was accompanied by decreased mRNA of pro-apoptotic genes and transcription factors (DIABLO, PMAIP1, BAX, CASP3, CASP7, RUNX3, E2F1, TP53) and increased anti-apoptotic CFLAR and BCL2A1 mRNA. TNF-α and sFas levels correlated with circulating apoptotic neutrophils and expression of apoptosis genes. Stimulation with TNF-α of neutrophils from controls significantly down-regulated E2F1 and CASP3 expression.
Conclusions: Circulating neutrophils in GPA have anti-apoptotic phenotype involving both intrinsic and extrinsic pathways of apoptosis. This is accompanied by increased levels of circulating pro-survival factors (GM-CSF, TNF-α, sFas), independent of disease activity. Anti-apoptotic phenotype of neutrophils in GPA is reproduced by exposure to low concentrations of TNF-α.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objective
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors ...influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers—members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS).
Methods
We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population).
Results
Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02–19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7).
Conclusions
In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.
There has been a growing interest in research concerning memory modification technologies (MMTs) in recent years. Neuroscientists and psychologists are beginning to explore the prospect of ...controllable and intentional modification of human memory. One of the technologies with the greatest potential to this end is optogenetics-an invasive neuromodulation technique involving the use of light to control the activity of individual brain cells. It has recently shown the potential to modify specific long-term memories in animal models in ways not yet possible with other MMTs. As the therapeutic potential of optogenetics has already prompted approval of the first human trials, it is especially important and timely to consider the opportunities and dangers this technology may entail. In this article, we focus on possible consequences of optogenetics as an MMT by analyzing fundamental threats potentially associated with memory modifications: the potential disruption of personality and authenticity.
PDF
