Sequential polarization and imprinting of type 1 T-helper lymphocytes by interferon-γ and interleukin-12

Differentiation of naive T lymphocytes into type I T helper (Th1) cells requires interferon-γ and interleukin-12. It is puzzling that interferon-γ induces the Th1 transcription factor T-bet, whereas interleukin-12 mediates Th1 cell lineage differentiation. We use mathematical modeling to analyze the expression kinetics of T-bet, interferon-γ, and the IL-12 receptor β2 chain (IL-12Rβ2) during Th1 cell differentiation, in the presence or absence of interleukin-12 or interferon-γ signaling. We show that interferon-γ induced initial T-bet expression, whereas IL-12Rβ2 was repressed by T cell receptor (TCR) signaling. The termination of TCR signaling permitted upregulation of IL-12Rβ2 by T-bet and interleukin-12 signaling that maintained T-bet expression. This late expression of T-bet, accompanied by the upregulation of the transcription factors Runx3 and Hlx, was required to imprint the Th cell for interferon-γ re-expression. Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-γ-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling

Дифракционный метод контроля диаметра протяженных изделий

Задача работы состоит в обзоре современных методов и средств измерения геометрических параметров изделий и исследовании некоторых аспектов применения интерференционных методов, позволяющих по распределению дифракционных экстремумов получать значение контролируемого геометрического параметра.The task of the paper is to review modern methods and tools for measuring the geometric parameters of products and to study certain aspects of the application of interference methods that allow one to obtain the value of a controlled geometric parameter from the distribution of diffraction extrema

Is the blue tit falling into an ecological trap in Argentine ant invaded forests?

Because insectivorous birds must evaluate resources for reproduction before settling into a breed- ing habitat, they can fall into an ecological trap if informative cues about habitat suitability become dissociated from their actual yield. Given their potential to affect ecological networks, invasive ant species are potential candidates for triggering such ecological traps. We combined observational and experimental approaches to examine whether the variation in food supply for nestlings resulting from the invasion of the Argentine ant, Linepithema humile, had any influence on the breeding ecology of the blue tit, Cyanistes caeruleus, an insectivorous foliage-gleaner. We inves- tigated the effects of the ant invasion on breeding performance (nesting success, clutch size, brood size and breeding success) and offspring quality (body size and condition, developmental stability and plumage colour) in replicated Mediterranean forest areas over a period of 3 years. There was no evidence that the reduction in caterpillar availability resulting from the invasion had a concurrent negative effect on the blue tit’s ability to successfully rear nestlings in optimal conditions, at least as measured here. Although the raw figures suggest an increased level of nutritional stress in blue tits breeding in invaded forests, the data analyses showed no significant alterations in terms of productiv- ity or offspring fitness. The reproductive performance of the blue tit has been shown to be remarkably resilient to the Argentine ant-mediated food shortage, either because the prey reduction following the invasion did not reach a critical threshold or because of compensa- tory activity by the progenitors. We cannot conclusively reject an ecological trap triggered by the ant invasion on blue tits, since neither fledgling recruitment nor the prospective survival of parents were assessed. Even though we could not confirm short-term consequences of the Argentine ant invasion on blue tit reproductive fitness, the long-term bottom-up effects of the invasion remain unknown and should not be ruled outPeer reviewe

Factors Affecting The Efficiency Of Fox (Vulpes Vulpes) Baiting Practices On The Central Tablelands Of New South Wales

The European red fox (Vulpes vulpes L.) is a well known predator of native species and domestic stock, and is recognised as one of Australia’s most devastating vertebrate pests. Current fox management relies heavily on poisoning using baits impregnated with sodium monofluoroacetate (1080). This reliance on 1080 is likely to continue given the lack of viable alternatives for controlling foxes, so that, in the meanwhile, it is important to improve the efficiency of the current techniques. Factors affecting the susceptibility of individual foxes to bait include their ability to locate it, as well as the bait’s palatability and toxicity. The economic costs associated with using different bait types, the pattern and density of their distribution will also affect the efficiency of control programs. It is essential to examine and refine all such issues to ensure efficient use of the 1080 baiting technique. This thesis focuses generally on problems associated with management of the fox in eastern Australia. More specifically, I investigate the factors affecting the efficiency of fox baiting practices on the central tablelands of New South Wales. The study was conducted largely on agricultural lands near the town of Molong (33010’ 37”S, 148087’15”E) on the central tablelands of New South Wales. This area was chosen as it is broadly representative, in terms of land use, of a large region of eastern Australia. The highly modified, predominantly agricultural landscapes near Molong are well suited to foxes, and conflict with the predominantly pastoral community means that fox management is widely undertaken. I determined the persistence of 1080 in two commonly used bait types, Foxoff® and chicken wingettes, under different climatic and rainfall conditions. The rate of 1080 degradation did not change significantly between the central tablelands and the relatively hotter and drier western slopes. Foxoff® baits remained lethal for longer than wingettes under all conditions, although their rate of degradation generally increased with increasing rainfall. I confirmed the presence of defluorinating micro-organisms in thesoils of eastern Australia for the first time, and suggest that, following removal from the bait, 1080 would not persist in the environment for long. Bait should be attractive and highly palatable to ensure that the target species will find and consume it upon discovery. Caching, where discovered food is removed but not immediately consumed, may potentially reduce the efficacy and cost-effectiveness of baiting campaigns. I quantified the caching of chicken wingette, day-old chick and Foxoff® baits by inserting transmitters into bait material and assessing whether it was eaten or cached following removal. The intensity of caching did not change significantly between seasons. Type of bait had the largest influence on caching intensity, with a greater percentage of non-toxic Foxoff® baits (66.9%) being cached than either wingettes (5.7%) or day-old chicks (4.5%). The percentage of toxic (1080) baits cached was even greater, suggesting that 1080 bait may be less palatable, and detectable to foxes. I also investigated the use of conditioned taste aversion to reduce multiple bait uptake by foxes. Levamisole, an illness-inducing chemical, was added to bait and the fate of removed bait was again monitored via radio-telemetry. Following consumption of a levamisole-treated bait, foxes avoided eating treated baits but consumed untreated baits. I concluded that a reduction in bait consumption was achieved through learned aversion to levamisole rather than via conditioned taste aversion to baits. Adding levamisole to baits, especially non-toxic bait such as rabies vaccines, could potentially be used to reduce bait monopolisation by individual foxes. Fox density and den site preferences were assessed by investigating the distribution and density of fox natal dens on one property (9.6 km2) over three consecutive years. A total of 9 natal dens were located in 2000 and 2001, declining to 6 in 2002. No preference was shown for den sites on the basis of habitat, slope or aspect, but more dens were located under, or adjacent to cover. Assuming that each natal den represents a breeding pair and that the population sex ratio did not differ from parity (1:1), the site contained a prebreeding density of 1.9 foxes/km2 in 2000 and 2001, and 1.25 foxes/km2 in 2002. Given that the mean number of cubs is 4.0, the post-breeding density was estimated at 5.6 and 3.75 foxes/km2 in 2000/2001 and 2002, respectively. The results demonstrated that high densities of foxes occur on agricultural lands. The success and likely accuracy of the technique to monitor fox density suggests that it may be used to calibrate more efficient abundance estimates that will be essential for the strategic management of foxes in future. Pest animal management strategies are traditionally assessed for their effectiveness, with less consideration being given to the efficiency or cost of achieving the desired effect. I used cost-effectiveness analyses to compare between different baiting strategies based on the longevity, palatability and handling/replacement costs associated with each bait type. The results indicated that, when measured on a total cost-per-bait-consumed basis, wingettes and day-old chicks were the most cost-effective baits for campaigns of up to 4 weeks duration. This demonstrates the importance of including the longevity, and particularly the palatability of bait, when assessing cost-effectiveness. However, it is recognised that other factors, including the consistency of dosage and uptake by nontarget species, may be equally or more important in deciding the appropriate baiting strategy. The spatial and temporal application of fox baiting in the region overseen by the Molong Rural Lands Protection Board was examined between January 1998 and December 2002 as a case study to evaluate the apparent effectiveness of cooperative management practices. Most landholders (78.8%) did not bait for foxes during this period. Based on known dispersal distances, the effect of fox immigration into baited areas was determined. The results indicated that no areas baited for foxes were separated by a sufficient buffer distance (>9.58 km) from unbaited areas to be protected from fox immigration. This suggests that, at current levels of coordination, the effectiveness of most baiting operations in eastern Australia is compromised over the long term by fox immigration. However, it is recognised that short-term reductions in fox density may sometimes be all that are required to reduce predation to acceptable levels, especially for seasonally-susceptible prey. Ultimately, the cost-effectiveness of control should be evaluated in terms of the response of the prey rather than that of the predator. This study has highlighted deficiencies in current ‘best-practice’ baiting techniques. Specific recommendations for current baiting practices, in addition to future research, are also given. In brief, these include minimising free-feed baiting, increasing the minimum distance between bait stations, and, where possible, presenting the most palatable bait. Continued research into conditioned taste aversion, aerial baiting, and techniques to reduce caching are recommended as potential techniques to improve the efficiency of baiting practices

Humour interventions for patients in palliative care-a randomized controlled trial.

PURPOSE: The effect of humour on end-of-life patients could be beneficial and is worth investigating. However, data on humour interventions for patients in palliative care are scarce. This study evaluated the effects of a humour intervention in a palliative care setting. METHODS: A two-step intervention was developed based on the humour habits programme by McGhee. Patients were assisted to remember funny episodes from their past and recognize humorous aspects of the present and encouraged to produce humour. The intervention and control group completed questionnaires on life satisfaction, cheerfulness, symptom burden, and perceived stress and if possible gave saliva samples to investigate oxytocin levels. The study was a randomized controlled monocentre study on patients treated in a palliative care ward. Participants had to be conscious and alert enough to complete data collection. Overall, 55 patients were included and randomized to the intervention or control group. RESULTS: Parameters in the control group did not change significantly. In the intervention group, seriousness, bad mood, and stress were reduced. Cheerfulness increased significantly after the intervention. However, the methodologically complex intervention setting was too exhausting for the majority of patients. CONCLUSION: Patients who were able to participate benefited from the effects of the intervention on multiple levels. For future research simple interventions, biomarkers for well-being and assessments by staff or proxies are needed to include patients with reduced cognitive and physical performance status at the end of their lives. TRIAL REGISTRATION: DRKS00028978 German Registry of Clinical Studies

Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14-CD15(high) and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16(hi) LDGs. Clinical data on disease course, medication, and antibody status were obtained. Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group. Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD