The witchcraft trial in Moscow

https://stars.library.ucf.edu/prism/1519/thumbnail.jp

Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer

Background. Fibronectin type III domain-containing (FNDC) proteins fulfill manifold functions in tissue development and regulation of cellular metabolism. FNDC4 was described as anti-inflammatory factor, upregulated in inflammatory bowel disease (IBD). FNDC signaling includes direct cell-cell interaction as well as release of bioactive peptides, like shown for FNDC4 or FNDC5. The G-protein-coupled receptor 116 (GPR116) was found as a putative FNDC4 receptor. We here aim to comprehensively analyze the mRNA expression of FNDC1, FNDC3A, FNDC3B, FNDC4, FNDC5, and GPR116 in nonaffected and affected mucosal samples of patients with IBD or colorectal cancer (CRC). Methods. Mucosa samples were obtained from 30 patients undergoing diagnostic colonoscopy or from surgical resection of IBD or CRC. Gene expression was determined by quantitative real-time PCR. In addition, FNDC expression data from publicly available Gene Expression Omnibus (GEO) data sets (GDS4296, GDS4515, and GDS5232) were analyzed. Results. Basal mucosal expression revealed higher expression of FNDC3A and FNDC5 in the ileum compared to colonic segments. FNDC1 and FNDC4 were significantly upregulated in IBD. None of the investigated FNDCs was differentially expressed in CRC, just FNDC3A trended to be upregulated. The GEO data set analysis revealed significantly downregulated FNDC4 and upregulated GPR116 in microsatellite unstable (MSI) CRCs. The expression of FNDCs and GPR116 was independent of age and sex. Conclusions. FNDC1 and FNDC4 may play a relevant role in the pathobiology of IBD, but none of the investigated FNDCs is regulated in CRC. GPR116 may be upregulated in advanced or MSI CRC. Further studies should validate the altered FNDC expression results on protein levels and examine the corresponding functional consequences

Long-term adherence to pessary use in women with pelvic organ prolapse: A retrospective cohort study

Purpose of the research: Vaginal pessary use is an established, non-surgical treatment option for pelvic organ prolapse. While satisfaction rates are initially high, they seem to decline over time. We aimed to determine the median duration of pessary use among our patients and to evaluate reasons for discontinuation. Methods: All patients who were treated with a vaginal pessary for pelvic organ prolapse between 2007 and 2022 at our institution (a maximum observation period of 15 years) were included in this retrospective cohort study. Data were collected from the in-house electronic databases and the date of pelvic floor surgery was defined as the primary endpoint. In case of no documented surgery, the date of the last follow-up visit (for patients lost to follow-up or who discontinued pessary use without subsequent surgery) or the date of final data collection (for those with presumed continued pessary use) was used as the primary endpoint. Duration of pessary use is represented by Kaplan-Meier curves. Effects of possible confounders were investigated by Cox regression models. A Cox regression model was evaluated for patients with the three most common types of pessary: ring, cube and shell. A chi-square test was performed to compare therapy adherence according to pessary type. Principal results: Data of 779 patients could be included in the statistical analysis. The estimated median duration of pessary use was 173 weeks (95 % CI 104-473) - approximately 3.3 years. Overall, 30 % of patients opted for surgical therapy and the majority of them did so within 4 months of initiation of pessary use (median time: 19 weeks, 95 % CI 16-26). In 5 % of cases a discontinuation of pessary use without subsequent surgery was documented and 18 % were lost to follow-up before a planned visit, thus leaving 47 % of our patients with presumed continued pessary use. Possible confounding factors for discontinuation of pessary use were tested but were found to be non-significant (body mass index, Pelvic Organ Prolapse - Quantification score, pelvic floor training, age, parity, menopausal status, nicotine consumption, incontinence or size of pessary). Reasons for discontinuation of pessary use were documented in 51 % of patients: unspecified patient wish (23 %), pessary use tiredness (10 %), general dissatisfaction with pessary therapy (7 %), unspecified reasons (5 %), pessary self-change not possible (1 %), erosion, bleeding, pain (2 %); none of the pessary types fitted (2 %). Conclusions: According to our data, almost half of our patients with pelvic organ prolapse and pessary therapy continued pessary use until a maximum follow-up time of 15 years, whereas about one-third of patients finally opted for surgical repair (a majority of these within 4 months after pessary therapy initiation). The remaining patients were either lost to follow-up or discontinued pessary use without subsequent surgery. The stated reasons for discontinuation of pessary use were mostly non-specific, but only 1 % reported that pessary self-change was not possible. Erosion bleeding or pain was documented in only 2 % of cases as reason for discontinuation. This information helps clinicians to inform their patients with pelvic organ prolapse about expected pessary therapy success and strengthens individual counselling. Furthermore, our data indicates vaginal pessary use for pelvic organ prolapse is feasible and safe for all women and that therapy adherence can extend beyond 5 years

Perturbation of Lytic and Latent Gammaherpesvirus Infection in the Absence of the Inhibitory Receptor CEACAM1

Control of gammaherpesvirus infections requires a complex, well orchestrated immune response regulated by positive and negative co-signaling molecules. While the impact of co-stimulatory molecules has been addressed in various studies, the role of co-inhibitory receptors has not been tested. The ITIM-bearing CEACAM1 is an inhibitory receptor expressed by a variety of immune cells, including B, T and NK cells. Using Ceacam1−/− mice, we analyzed the in vivo function of CEACAM1 during acute and latent murine gammaherpesvirus 68 (MHV-68) infection. During acute lytic replication, we observed lower virus titers in the lungs of Ceacam1−/− mice than in WT mice. In contrast, during latency amplification, Ceacam1−/− mice displayed increased splenomegaly and a higher latent viral load in the spleen. Analysis of the immune response revealed increased virus-specific antibody levels in Ceacam1−/− mice, while the magnitude of the T cell-mediated antiviral immune response was reduced. These findings suggest that inhibitory receptors can modulate the efficacy of immune responses against gammaherpesvirus infections

On logical hierarchies within FO^2-definable languages

We consider the class of languages defined in the 2-variable fragment of the first-order logic of the linear order. Many interesting characterizations of this class are known, as well as the fact that restricting the number of quantifier alternations yields an infinite hierarchy whose levels are varieties of languages (and hence admit an algebraic characterization). Using this algebraic approach, we show that the quantifier alternation hierarchy inside FO^{2}[<] is decidable within one unit. For this purpose, we relate each level of the hierarchy with decidable varieties of languages, which can be defined in terms of iterated deterministic and co-deterministic products. A crucial notion in this process is that of condensed rankers, a refinement of the rankers of Weis and Immerman and the turtle languages of Schwentick, Th\'erien and Vollmer.Comment: arXiv admin note: text overlap with arXiv:0904.289

The International Mountain Conference, Innsbruck, Austria, September 2019 (IMC2019): A Synthesis with Recommendations for Research

This paper presents a synthesis of the outcomes of sessions and recommendations for future research in mountain areas from the International Mountain Conference (IMC), held in Innsbruck, Austria, in September 2019. The thematic sections of the paper consider: first, the paleosciences, particularly archaeology; second, (bio)physical systems—the climate system, the cryo- and hydrosphere, and the biosphere—and their relationships with human systems; third, natural hazards and risks; and fourth, demographic and sociocultural trends, globalization (energy and transport networks, tourism, food supplies), policymaking, development, and research. Each section includes key literature relating to its theme, together with recommendations from the respective sessions. The paper concludes with a discussion and conclusions on the process of producing the synthesis, and its value for preparation and synthesis strategies for future conferences

Dll1 Haploinsufficiency in Adult Mice Leads to a Complex Phenotype Affecting Metabolic and Immunological Processes

BACKGROUND: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized. CONCLUSIONS/SIGNIFICANCE: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes

From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes

Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users. Results: Here we present an ‘A to Z’ protocol for obtaining complete human mitochondrial (mtDNA) genomes – from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling). Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual ‘modules’ can be swapped out to suit available resources

Ancient DNA from European Early Neolithic Farmers Reveals Their Near Eastern Affinities

The first farmers from Central Europe reveal a genetic affinity to modern-day populations from the Near East and Anatolia, which suggests a significant demographic input from this area during the early Neolithic

Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice

Background: The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardiovascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Methods: Equivalent surface area CNP doses in the blood (30mm(2) per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm(2);accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [>= 98 and >= 95% elemental carbon;10 and 14 nm primary particle diameter;and 800 and 300 m(2)/g specific surface area] for inhalation and IAI respectively. Results: Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver);aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Conclusions: Our findings indicate that extra-pulmonary effects due to CNP inhalation are dominated by indirect effects (particle-cell interactions in the lung) rather than direct effects (translocated CNPs) within the first hours after exposure. Hence, CNP translocation may not be the key event inducing early cardiovascular impairment following air pollution episodes. The considerable response detected in the aorta after CNP inhalation warrants more emphasis on this tissue in future studies