Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally ...differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.
Hen welfare in different housing systems Lay, D.C. Jr; Fulton, R.M; Hester, P.Y ...
Poultry science,
2011, 2011-Jan, 2011-01-00, Letnik:
90, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Egg production systems have become subject to heightened levels of scrutiny. Multiple factors such as disease, skeletal and foot health, pest and parasite load, behavior, stress, affective states, ...nutrition, and genetics influence the level of welfare hens experience. Although the need to evaluate the influence of these factors on welfare is recognized, research is still in the early stages. We compared conventional cages, furnished cages, noncage systems, and outdoor systems. Specific attributes of each system are shown to affect welfare, and systems that have similar attributes are affected similarly. For instance, environments in which hens are exposed to litter and soil, such as noncage and outdoor systems, provide a greater opportunity for disease and parasites. The more complex the environment, the more difficult it is to clean, and the larger the group size, the more easily disease and parasites are able to spread. Environments such as conventional cages, which limit movement, can lead to osteoporosis, but environments that have increased complexity, such as noncage systems, expose hens to an increased incidence of bone fractures. More space allows for hens to perform a greater repertoire of behaviors, although some deleterious behaviors such as cannibalism and piling, which results in smothering, can occur in large groups. Less is understood about the stress that each system imposes on the hen, but it appears that each system has its unique challenges. Selective breeding for desired traits such as improved bone strength and decreased feather pecking and cannibalism may help to improve welfare. It appears that no single housing system is ideal from a hen welfare perspective. Although environmental complexity increases behavioral opportunities, it also introduces difficulties in terms of disease and pest control. In addition, environmental complexity can create opportunities for the hens to express behaviors that may be detrimental to their welfare. As a result, any attempt to evaluate the sustainability of a switch to an alternative housing system requires careful consideration of the merits and shortcomings of each housing system.
A classification for peri‐implant diseases and conditions was presented. Focused questions on the characteristics of peri‐implant health, peri‐implant mucositis, peri‐implantitis, and soft‐ and ...hard‐tissue deficiencies were addressed.
Peri‐implant health is characterized by the absence of erythema, bleeding on probing, swelling, and suppuration. It is not possible to define a range of probing depths compatible with health; Peri‐implant health can exist around implants with reduced bone support.
The main clinical characteristic of peri‐implant mucositis is bleeding on gentle probing. Erythema, swelling, and/or suppuration may also be present. An increase in probing depth is often observed in the presence of peri‐implant mucositis due to swelling or decrease in probing resistance. There is strong evidence from animal and human experimental studies that plaque is the etiological factor for peri‐implant mucositis.
Peri‐implantitis is a plaque‐associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri‐implant mucosa and subsequent progressive loss of supporting bone. Peri‐implantitis sites exhibit clinical signs of inflammation, bleeding on probing, and/or suppuration, increased probing depths and/or recession of the mucosal margin in addition to radiographic bone loss.
The evidence is equivocal regarding the effect of keratinized mucosa on the long‐term health of the peri‐implant tissue. It appears, however, that keratinized mucosa may have advantages regarding patient comfort and ease of plaque removal.
Case definitions in day‐to‐day clinical practice and in epidemiological or disease‐surveillance studies for peri‐implant health, peri‐implant mucositis, and peri‐implantitis were introduced. The proposed case definitions should be viewed within the context that there is no generic implant and that there are numerous implant designs with different surface characteristics, surgical and loading protocols. It is recommended that the clinician obtain baseline radiographic and probing measurements following the completion of the implant‐supported prosthesis.
To assess risk of a first clinical diagnosis of CNS demyelination (FCD) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors.
This was a ...multicenter incident case-control study. FCD cases (n = 282) aged 18-59 years and controls (n = 558, matched on age, sex, and region) were recruited from 4 Australian centers between November 1, 2003, and December 31, 2006. A nested study (n = 215 cases, n = 216 controls) included measurement of whole blood quantitative EBV DNA load and serum EBV-specific antibodies. Conditional logistic regression was used to analyze case-control differences.
There were no significant case-control differences in the proportion with detectable EBV DNA (55.8% vs 50.5%, respectively, p = 0.28), or in quantitative EBV DNA load (p = 0.33). Consistent with previous work, higher anti-EBV-specific immunoglobulin G (IgG) titers and a history of infectious mononucleosis were associated with increased FCD risk and there was an additive interaction with HLA-DRB1*1501 status. We found additional interactions between high anti-EBNA IgG titer and SNPs in HLA-A (adjusted odds ratios AOR = 19.84 95% confidence interval (CI) 5.95 to 66.21 for both factors compared to neither) and CTLA-4 genes (AOR = 0.31 95% CI 0.13 to 0.76 for neither factor compared to both). EBV DNA load was lower at higher serum 25-hydroxyvitamin D concentrations in controls (r = -0.17, p = 0.01). An adverse effect of higher EBV DNA load on FCD risk was increased with higher 25-hydroxyvitamin D concentration (pinteraction = 0.02).
Past infection with EBV, but not current EBV DNA load in whole blood, is significantly associated with increased FCD risk. These associations appear to be modified by immune-related gene variants.
The phenomenon of core excitation in the breakup of a two-body halo nucleus is investigated. We show that this effect plays a significant role in the reaction dynamics and, furthermore, its ...interference with the valence excitation mechanism has sizable and measurable effects on the breakup angular distributions. These effects have been studied in the resonant breakup of (11)Be on a carbon target, populating the resonances at 1.78 MeV (5/2(+)) and 3.41 MeV (3/2(+)). The calculations have been performed using a recent extension of the distorted-wave Born approximation method, which takes into account the effect of core excitation in both the structure of the halo nucleus and in the reaction mechanism. The calculated angular distributions have been compared with the available data Fukuda et al., Phys. Rev. C 70, 054606 (2004).. Although each of these resonances is dominated by one of the two considered mechanisms, the angular patterns of these resonances depend in a very delicate way on the interference between them. This is the first clear evidence of this effect but the phenomenon is likely to occur in other similar reactions.
Potato type I and II serine protease inhibitors are produced by solanaceous plants as a defense mechanism against insects and microbes. Nicotiana alata proteinase inhibitor (NaPI) is a multidomain ...potato type II inhibitor (pin II) that is produced at high levels in the female reproductive tissues of the ornamental tobacco, Nicotiana alata. The individual inhibitory domains of NaPI target the major classes of digestive enzymes, trypsin and chymotrypsin, in the gut of lepidopteran larval pests. Although consumption of NaPI dramatically reduced the growth and development of a major insect pest, Helicoverpa punctigera, we discovered that surviving larvae had high levels of chymotrypsin activity resistant to inhibition by NaPI. We found a potato type I inhibitor, Solanum tuberosum potato type I inhibitor (StPin1A), was a strong inhibitor of the NaPI-resistant chymotrypsin activity. The combined inhibitory effect of NaPI and StPin1A on H. armigera larval growth in the laboratory was reflected in the increased yield of cotton bolls in field trials of transgenic plants expressing both inhibitors. Better crop protection thus is achieved using combinations of inhibitors in which one class of proteinase inhibitor is used to match the genetic capacity of an insect to adapt to a second class of proteinase inhibitor.
Sidestepping in response to unplanned stimuli is a high‐risk maneuver for anterior cruciate ligament (ACL) injuries. Yet, differences in body reorientation strategies between high‐ and low‐level ...soccer players prior to sidestepping in response to quasi‐game‐realistic vs non‐game‐realistic stimuli, remain unknown. Fifteen high‐level (semi‐professional) and 15 low‐level (amateur) soccer players responded to a quasi‐game‐realistic one‐defender scenario (1DS) and two‐defender scenario (2DS), and non‐game‐realistic arrow‐planned condition (AP) and arrow‐unplanned condition (AUNP). The AP, 1DS, 2DS to AUNP represented increasing time constraints to sidestep. Selected biomechanics from the penultimate step to foot‐off were assessed using a mixed‐model (stimuli × skill) ANOVA (P < 0.05). Step length decreased in the defender scenarios compared with the arrow conditions. Support foot placement increased laterally, away from mid‐pelvis, with increasing temporal constraints. Greater trunk lateral flexion in the 1DS, 2DS, and AUNP has been associated with ACL injury onsets. Higher level players pushed off closer to their pelvic midline at initial foot contact in the 2DS especially. Higher level perception of game‐realistic visual information could have contributed to this safer neuromuscular strategy that, when understood better, could potentially be trained in lower level players to reduce ACL injury risk associated with dangerous sidestepping postures.
Background
Around 0.5% of cutaneous melanoma (CM) patients will present with synchronous melanomas when first seen. Moreover, 26–40% of patients with multiple primary melanomas present with ...synchronous lesions.
Objectives
To assess the prevalence, clinical and histopathological characteristics, germline mutations and outcome in patients with synchronous melanoma.
Methods
Clinical and histopathological data from 4703 melanoma patients were included. Clinical, histological and genetic mutational status information was analysed. Kaplan–Meier curves were used to investigate survival outcomes.
Results
A total of 144 patients (3.06%) presented simultaneously with two or more primary melanomas. During follow‐up, 25.7% of patients with synchronous melanoma developed a new primary melanoma compared to 8.6% of patients diagnosed with single melanoma (P < 0.001). Germinal CDKN2A mutations were identified in 10.7% of patients with synchronous melanomas and genetic variants in MC1R in 72%. No significant differences in all survival outcomes between patients with synchronous melanomas and single melanomas were found.
Conclusion
Synchronous melanomas are more frequent than previously reported and are more frequent in older patients compared to single melanomas. Moreover, these patients have a higher risk of developing a new primary melanoma during follow‐up and have higher rates of germline susceptibility variants. Nevertheless, these findings were not associated with worse outcomes.
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