B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Mice with Mutation in Dynein Heavy Chain 1 Do Not Share the Same Tau Expression Pattern with Mice with SOD1-Related Motor Neuron Disease

Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/SOD1) mutations and wild-type controls. Total tau-mRNA and isoforms 0, 1 and 2 N expression was studied in frontal cortex, hippocampus, spinal cord and cerebellum of presymptomatic and symptomatic animals (age 70, 140 and 365 days). The most significant differences were found in brain cortex and cerebellum, but not in hippocampus and spinal cord. There were less changes in Cra1/SOD1 double heterozygotes compared to mice harboring single mutations. The differences in total tau expression and in profile of its isoforms between Cra1/+ and SOD1/+ transgenics indicate a distinct pathogenic entity of these two conditions

Density of Gr1-positive myeloid precursor cells, p-STAT3 expression and gene expression pattern in canine mammary cancer metastasis

The very recent studies on human and mice models have indicated an important role of myeloid precursor cells (progenitors or not fully differentiated cells that express the Gr1 antigen also called Gr1-positive myeloid suppressor cells) in the tumor progression and metastasis. They are thought to suppress the immune system and promote angiogenesis via Signal transducer and activator of transcription 3 (STAT3) activation. As of now there is no data available on the correlation of Gr1-positive cell number, phosphorylated STAT3 (p-STAT3) expression and cancer ability to metastasis. Thus, we counted the myeloid precursor cell number and analyzed p-STAT3 expression in 50 canine mammary tumors that gave local/distant metastases and did not metastasize. We showed that the number of Gr1-positive cells and p-STAT3 expression are significantly higher (p < 0.001) in the metastatic tumors than in the non-metastatic ones. We also observed higher expression of p-STAT3 in the canine mammary cancer cell lines with metastatic potential than in other cell lines (p < 0.001). Moreover, the number of myeloid precursors and p-STAT3 expression in metastatic tumors correlate strongly. The tumor infiltrating myeloid precursor cells may invigorate the STAT3 activity (probably via vascular endothelial growth factor – VEGF) that contributes to the tumor angiogenesis and furthermore tumor`s ability to metastasize. The analysis of gene expression in canine mammary cancer cell lines with metastatic potential indicated that semaphorin 3B (SEMA3B) and neuropilin receptors (NRP) may also be important elements in this process. Thus, we discuss the possible interactions within the tumor that may be required for cancer metastatis

Two new aflatoxin producing species, and an overview of Aspergillus section Flavi

Aspergillus subgenus Circumdati section Flavi includes species with usually biseriate conidial heads, in shades of yellow-green to brown, and dark sclerotia. Several species assigned to this section are either important mycotoxin producers including aflatoxins, cyclopiazonic acid, ochratoxins and kojic acid, or are used in oriental food fermentation processes and as hosts for heterologous gene expression. A polyphasic approach was applied using morphological characters, extrolite data and partial calmodulin, β-tubulin and ITS sequences to examine the evolutionary relationships within this section. The data indicate that Aspergillus section Flavi involves 22 species, which can be grouped into seven clades. Two new species, A. pseudocaelatus sp. nov. and A. pseudonomius sp. nov. have been discovered, and can be distinguished from other species in this section based on sequence data and extrolite profiles. Aspergillus pseudocaelatus is represented by a single isolate collected from Arachis burkartii leaf in Argentina, is closely related to the non-aflatoxin producing A. caelatus, and produces aflatoxins B & G, cyclopiazonic acid and kojic acid, while A. pseudonomius was isolated from insects and soil in the USA. This species is related to A. nomius, and produces aflatoxin B1 (but not G-type aflatoxins), chrysogine and kojic acid. In order to prove the aflatoxin producing abilities of the isolates, phylogenetic analysis of three genes taking part in aflatoxin biosynthesis, including the transcriptional regulator aflR, norsolonic acid reductase and O-methyltransferase were also carried out. A detailed overview of the species accepted in Aspergillus section Flavi is presented

Transcriptional activity of Hyacinthus orientalis L. female gametophyte cells before and after fertilization

We characterized three phases of Hyacinthus orientalis L. embryo sac development, in which the transcriptional activity of the cells differed using immunolocalization of incorporated 5′-bromouracil, the total RNA polymerase II pool and the hypo- (initiation) and hyperphosphorylated (elongation) forms of RNA Pol II. The first stage, which lasts from the multinuclear stage to cellularization, is a period of high transcriptional activity, probably related to the maturation of female gametophyte cells. The second stage, encompassing the period of embryo sac maturity and the progamic phase, involves the transcriptional silencing of cells that will soon undergo fusion with male gametes. During this period in the hyacinth egg cell, there are almost no newly formed transcripts, and only a small pool of RNA Pol II is present in the nucleus. The transcriptional activity of the central cell is only slightly higher than that observed in the egg cell. The post-fertilization stage is related to the transcriptional activation of the zygote and the primary endosperm cell. The rapid increase in the pool of newly formed transcripts in these cells is accompanied by an increase in the pool of RNA Pol II, and the pattern of enzyme distribution in the zygote nucleus is similar to that observed in the somatic cells of the ovule. Our data, together with the earlier results of Pięciński et al. (2008), indicate post-fertilization synthesis and the maturation of numerous mRNA transcripts, suggesting that fertilization in H. orientalis induces the activation of the zygote and endosperm genomes

Chemical, Physical and Biological Approaches to Prevent Ochratoxin Induced Toxicoses in Humans and Animals

Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard to animals and humans. Several strategies have been investigated for lowering the ochratoxin content in agricultural products. These strategies can be classified into three main categories: prevention of ochratoxin contamination, decontamination or detoxification of foods contaminated with ochratoxins, and inhibition of the absorption of consumed ochratoxins in the gastrointestinal tract. This paper gives an overview of the strategies that are promising with regard to lowering the ochratoxin burden of animals and humans

Movements of marine fish and decapod crustaceans: Process, theory and application

Many marine species have a multi-phase ontogeny, with each phase usually associated with a spatially and temporally discrete set of movements. For many fish and decapod crustaceans that live inshore, a tri-phasic life cycle is widespread, involving: (1) the movement of planktonic eggs and larvae to nursery areas; (2) a range of routine shelter and foraging movements that maintain a home range; and (3) spawning migrations away from the home range to close the life cycle. Additional complexity is found in migrations that are not for the purpose of spawning and movements that result in a relocation of the home range of an individual that cannot be defined as an ontogenetic shift. Tracking and tagging studies confirm that life cycle movements occur across a wide range of spatial and temporal scales. This dynamic multi-scale complexity presents a significant problem in selecting appropriate scales for studying highly mobile marine animals. We address this problem by first comprehensively reviewing the movement patterns of fish and decapod crustaceans that use inshore areas and present a synthesis of life cycle strategies, together with five categories of movement. We then examine the scale-related limitations of traditional approaches to studies of animal-environment relationships. We demonstrate that studies of marine animals have rarely been undertaken at scales appropriate to the way animals use their environment and argue that future studies must incorporate animal movement into the design of sampling strategies. A major limitation of many studies is that they have focused on: (1) a single scale for animals that respond to their environment at multiple scales or (2) a single habitat type for animals that use multiple habitat types. We develop a hierarchical conceptual framework that deals with the problem of scale and environmental heterogeneity and we offer a new definition of 'habitat' from an organism-based perspective. To demonstrate that the conceptual framework can be applied, we explore the range of tools that are currently available for both measuring animal movement patterns and for mapping and quantifying marine environments at multiple scales. The application of a hierarchical approach, together with the coordinated integration of spatial technologies offers an unprecedented opportunity for researchers to tackle a range of animal-environment questions for highly mobile marine animals. Without scale-explicit information on animal movements many marine conservation and resource management strategies are less likely to achieve their primary objectives

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049