946 research outputs found
No-passing Rule in the Ground State Evolution of the Random-Field Ising Model
We exactly prove the no-passing rule in the ground state evolution of the
random-field Ising model (RFIM) with monotonically varying external field. In
particular, we show that the application of the no-passing rule can speed up
the calculation of the zero-temperature equilibrium curve dramatically.Comment: 7 pages, 4 figure
Insights into the Pathology of the α3 Na+/K+-ATPase Ion Pump in Neurological Disorders; Lessons from Animal Models
Transcripts Encoding the Androgen Receptor and IGF-Related Molecules Are Differently Expressed in Human Granulosa Cells From Primordial and Primary Follicles
Bidirectional cross talk between granulosa cells and oocytes is known to be important in all stages of mammalian follicular development. Insulin-like growth factor (IGF) signaling is a prominent candidate to be involved in the activation of primordial follicles, and may be be connected to androgen-signaling. In this study, we interrogated transcriptome dynamics in granulosa cells isolated from human primordial and primary follicles to reveal information of growth factors and androgens involved in the physiology of ovarian follicular activation. Toward this, a transcriptome comparison study on primordial follicles (n = 539 follicles) and primary follicles (n = 261 follicles) donated by three women having ovarian tissue cryopreserved before chemotherapy was performed. The granulosa cell contribution in whole follicle isolates was extracted in silico. Modeling of complex biological systems was performed using IPA® software. We found the granulosa cell compartment of the human primordial and primary follicles to be extensively enriched in genes encoding IGF-related factors, and the Androgen Receptor (AR) enriched in granulosa cells of primordial follicles. Our study hints the possibility that primordial follicles may indeed be androgen responsive, and that the action of androgens represents a connection to the expression of key players in the IGF-signaling pathway including IGF1R, IGF2, and IGFBP3, and that this interaction could be important for early follicular activation. In line with this, several androgen-responsive genes were noted to be expressed in both oocytes and granulosa cells from human primordial and primary follicle. We present a detailed description of AR and IGF gene activities in the human granulosa cell compartment of primordial and primary follicles, suggesting that these cells may be or prepare to be responsive toward androgens and IGFs
Transcriptome Analysis of Long Non-coding RNAs and Genes Encoding Paraspeckle Proteins During Human Ovarian Follicle Development
Emerging evidence indicated that many long non-coding (lnc)RNAs function in multiple biological processes and dysregulation of their expression can cause diseases. Most regulatory lncRNAs interact with biological macromolecules such as DNA, RNA, and protein. LncRNAs regulate gene expression through epigenetic modification, transcription, and posttranscription, through DNA methylation, histone modification, and chromatin remodeling. Interestingly, differential lncRNA expression profiles in human oocytes and cumulus cells was recently assessed, however, lncRNAs in human follicle development has not previously been described. In this study, transcriptome dynamics in human primordial, primary and small antral follicles were interrogated and revealed information of lncRNA genes. It is known that some lncRNAs form a complex with paraspeckle proteins and therefore, we extended our transcriptional analysis to include genes encoding paraspeckle proteins. Primordial, primary follicles and small antral follicles was isolated using laser capture micro-dissection from ovarian tissue donated by three women having ovarian tissue cryopreserved before chemotherapy. After RN sequencing, a bioinformatic class comparison was performed and primordial, primary and small antral follicles were found to express several lncRNA and genes encoding paraspeckle proteins. Of particular interest, we detected the lncRNAs XIST, NEAT1, NEAT2 (MALAT1), and GAS5. Moreover, we noted a high expression of FUS, TAF15, and EWS components of the paraspeckles, proteins that belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity, and mRNA/microRNA processing. We also interrogated the intra-ovarian localization of the FUS, TAF15, and EWS proteins using immunofluorescence. The presence and the dynamics of genes that encode lncRNA and paraspeckle proteins may suggest that these may mediate functions in the cyclic recruitment and differentiation of human follicles and could participate in biological processes known to be associated with lncRNAs and paraspeckle proteins, such as gene expression control, scaffold formation and epigenetic control through human follicle development. This comprehensive transcriptome analysis of lncRNAs and genes encoding paraspeckle proteins expressed in human follicles could potentially provide biomarkers of oocyte quality for the development of non-invasive tests to identify embryos with high developmental potential
Perceived Positive and Negative Life Changes in Testicular Cancer Survivors
Background and objectives: Despite a generally good prognosis, testicular cancer can be a
life-altering event. We explored perceived positive and negative life changes after testicular cancer in
terms of frequency, demographic and disease-related predictors, and associations with depression
and anxiety. Materials and methods: All testicular cancer survivors receiving follow-up care at two specialized
outpatient treatment facilities were approached at follow-up visits or via mail. We assessed
a total of N = 164 patients (66% participation rate, mean time since diagnosis: 11.6 years, SD = 7.4)
by the Posttraumatic Growth Inventory (PTGI, modified version assessing positive and negative
changes for each of 21 items), Patient-Health-Questionnaire-9 (PHQ-9), and Generalized-Anxiety-
Disorder-Scale-7 (GAD-7). We conducted controlled multivariate regression analyses. Results: Most
survivors (87%) reported at least one positive change (mean number: 7.2, SD = 5.0, possible range:
0–21). The most frequent perceived positive changes were greater appreciation of life (62%), changed
priorities in life (62%), and ability rely on others (51%). At least one negative change was perceived
by 33% (mean number of changes: 1.1, SD = 2.5). Negative changes were most frequent for decreases
in self-reliance (14%), personal strength (11%), and ability to express emotions (9%). A higher socioeconomic
status was associated with more positive changes ( = 0.25, 95% CI 0.08 to 0.42); no other
association with demographic and disease-related predictors emerged. While positive life changes
were not associated with depression ( = 0.05, 95% CI 0.17 to 0.07) and anxiety ( = 0.00, 95%
CI 0.13 to 0.13), more negative life changes were significantly associated with higher depression
( = 0.15, 95% CI 0.03 to 0.27) and anxiety ( = 0.23, 95% CI 0.11 to 0.36). There was no significant
interaction of positive and negative changes on depression or anxiety. Conclusions: Although positive
life changes after testicular cancer are common, a significant number of survivors perceive negative
changes in life domains that have been primarily investigated in terms of personal growth. Early
identification of and psychosocial support for patients who perceive predominantly negative changes
may contribute to prevention of prolonged symptoms of anxiety and depression
The shifting position of homeowners in flood resilience: From recipients to key-stakeholders
The academic debate on flood risk governance is paying increased attention to the shifting position of homeowners. Homeowners are increasingly expected to adapt their homes to protect against possible floods. Although an overall agreement seems to exist on the involvement of homeowners in flood risk governance, the academic literature is dispersed in its argumentation on why homeowners should be involved. Therefore, this article provides a coherent overview of the transition from flood protection to flood risk management, and subsequently of the arguments that unfold regarding the shifting position of homeowners within this debate. This overview, based on a systematic review of the academic literature, helps to shed light on the changing role of homeowners in flood risk governance and contributes to categorizing the arguments used in current academic reasoning on homeowner involvement in flood risk governance. We use a conceptual distinction between macro-level and micro-level arguments, and between individual and collective efforts to structure our results. This conceptual overview illustrates the potential gap in convincing homeowners of the urgency to take action, because the connection between the macro-level arguments (i.e., climate change and responsibility) and the micro-level arguments (i.e., minimizing flood damage on privately owned properties) is generally not made. We, therefore, suggest that a stronger coherence in the argumentation would contribute to increase homeowner awareness of their changing responsibilities, which might bring about a future shift toward a new phase in flood risk governance, in which the responsibilities of homeowners are more explicitly acknowledged and integrated into climate adaptation strategies. This article is categorized under: Engineering Water > Planning Water Human Water > Water Governance.</p
Comparison of real-time reverse transcriptase polymerase chain reaction of peripheral blood mononuclear cells, serum and cell-free body cavity effusion for the diagnosis of feline infectious peritonitis
Objectives Diagnosis of feline infectious peritonitis (FIP) remains challenging, especially in cats without effusions. The objective of this study was to evaluate the sensitivity and specificity of a real-time reverse transcriptase polymerase chain reaction (RT-PCR) detecting feline coronavirus (FCoV) RNA in peripheral blood mononuclear cells (PBMCs) and serum in comparison with the same real-time RT-PCR in cell-free body cavity effusion. Methods This prospective case-control study included 92 cats. Forty-three cats had a definitive diagnosis of FIP, established either by histopathological examination (n = 28) or by positive immunofluorescence staining of FCoV antigen in macrophages of effusions (n = 11), or by both methods (n = 4). Forty-nine control cats had other diseases but similar clinical signs. Real-time RT-PCR was performed on PBMCs of 37 cats (21 cats with FIP, 16 controls), on serum of 51 cats (26 cats with FIP, 25 controls) and on cell-free body cavity effusion of 69 cats (36 cats with FIP, 33 controls). Sensitivity, specificity, positive and negative predictive value, including 95% confidence intervals (CI), were calculated. Results Real-time RT-PCR of PBMCs, serum and cell-free body cavity effusion showed a specificity of 100% (95% CI 79.4-100% in PBMCs, 86.3-100% in serum, 89.4-100% in cell-free body cavity effusion) and a sensitivity of 28.6% (95% CI 11.3-52.2%) in PBMCs, 15.4% (95% CI 4.4-34.9%) in serum and 88.9% (95% CI 73.9-96.9%) in cell-free body cavity effusion to diagnose FIP. Conclusions and relevance Although it is known that RT-PCR can often provide false-positive results in healthy cats, this real-time RT-PCR was shown to be a specific tool for the diagnosis of FIP when applied in a clinical setting. Sensitivity in cell-free body cavity effusion was high but low in PBMCs and serum. PBMC samples showed a higher sensitivity than serum samples, and are therefore a better choice if no effusion is present
Maternally Contributed Folate Receptor 1 Is Expressed in Ovarian Follicles and Contributes to Preimplantation Development
Folates have been shown to play a crucial role for proper development of the embryo as folate deficiency has been associated with reduced developmental capacity such as increased risk of fetal neural tube defects and spontanous abortion. Transcripts encoding the reduced folate carrier RFC1 (SLC19A1 protein) and the high-affinity folate receptor FOLR1 are expressed in oocytes and preimplantation embryos, respectively. In this study, we observed maternally contributed FOLR1 protein during mouse and human ovarian follicle development, and 2-cell mouse embryos. In mice, FOLR1 was highly enriched in oocytes from primary, secondary and tertiary follicles, and in the surrounding granulosa cells. Interestingly, during human follicle development, we noted a high and specific presence of FOLR1 in oocytes from primary and intermediate follicles, but not in the granulosa cells. The distribution of FOLR1 in follicles was noted as membrane-enriched but also seen in the cytoplasm in oocytes and granulosa cells. In 2-cell embryos, FOLR1-eGFP fusion protein was detected as cytoplasmic and membrane-associated dense structures, resembling the distribution pattern observed in ovarian follicle development. Knock-down of Folr1 mRNA function was accomplished by microinjection of short interference (si)RNA targeting Folr1, into mouse pronuclear zygotes. This revealed a reduced capacity of Folr1 siRNA-treated embryos to develop to blastocyst compared to the siRNA-scrambled control group, indicating that maternally contributed protein and zygotic transcripts sustain embryonic development combined. In summary, maternally contributed FOLR1 protein appears to maintain ovarian functions, and contribute to preimplantation development combined with embryonically synthesized FOLR1
Modulation of Mast Cell Reactivity by Lipids: The Neglected Side of Allergic Diseases
Mast cells (MCs) have long been mainly regarded as effector cells in IgE-associated allergic disorders with potential immunoregulatory roles. Located close to the allergen entry sites in the skin and mucosa, MCs can capture foreign substances such as allergens, toxins, or noxious substances and are exposed to the danger signals produced by epithelial cells. MC reactivity shaped by tissue-specific factors is crucial for allergic responses ranging from local skin reactions to anaphylactic shock. Development of Th2 response leading to allergen-specific IgE production is a prerequisite for MC sensitization and induction of FcεRI-mediated MC degranulation. Up to now, IgE production has been mainly associated with proteins, whereas lipids present in plant pollen grains, mite fecal particles, insect venoms, or food have been largely overlooked regarding their immunostimulatory and immunomodulatory properties. Recent studies, however, have now demonstrated that lipids affect the sensitization process by modulating innate immune responses of epithelial cells, dendritic cells, and NK-T cells and thus crucially contribute to the outcome of sensitization. Whether and how lipids affect also MC effector functions in allergic reactions has not yet been fully clarified. Here, we discuss how lipids can affect MC responses in the context of allergic inflammation. Direct effects of immunomodulatory lipids on MC degranulation, changes in local lipid composition induced by allergens themselves and changes in lipid transport affecting MC reactivity are possible mechanisms by which the function of MC might be modulated
Comparison of Eight Commercially Available Faecal Point-of-Care Tests for Detection of Canine Parvovirus Antigen
A real-time polymerase chain reaction (qPCR) is considered the gold standard for the laboratory diagnosis of canine parvovirus (CPV) infection but can only be performed in specialized laboratories. Several point-of-care tests (POCT), detecting CPV antigens in faeces within minutes, are commercially available. The aim of this study was to evaluate eight POCT in comparison with qPCR. Faecal samples of 150 dogs from three groups (H: 50 client-owned, healthy dogs, not vaccinated within the last four weeks; S: 50 shelter dogs, healthy, not vaccinated within the last four weeks; p = 50 dogs with clinical signs of CPV infection) were tested with eight POCT and qPCR. Practicability, sensitivity, specificity, positive (PPV) and negative predictive values (NPV), as well as overall accuracy were determined. To assess the differences between and agreement among POCT, McNemar’s test and Cohen’s Kappa statistic were performed. Specificity and PPV were 100.0% in all POCT. Sensitivity varied from 22.9–34.3% overall and from 32.7–49.0% in group P. VetexpertRapidTestCPVAg® had the highest sensitivity (34.3% overall, 49.0% group P) and differed significantly from the 3 POCT with the lowest sensitivities (Fassisi®Parvo (27.7% overall, 36.7% group P), Primagnost®ParvoH+K (24.3% overall, 34.7% group P), FASTest®PARVOCard (22.9% overall, 32.7% group P)). The agreement among all POCT was at least substantial (kappa >0.80). A positive POCT result confirmed the infection with CPV in unvaccinated dogs, whereas a negative POCT result did not definitely exclude CPV infection due to the low sensitivity of all POCT
- …