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Abstract A soil bacterium in the Serratia genus, carrying a 153 kb conjugative amber disease‐associated plasmid (pADAP), is commercially exploited for population control of the New Zealand endemic pest beetle Costelytra giveni (Coleoptera: Scarabaeidae). The main insecticidal elements are an anti‐feeding prophage and the Sep ABC toxin complex (Tc). Homologs of pADAP, encoding variant Tcs, convey different beetle disease phenotypes. To investigate the correlation between variable bioactivity and the Tc variant, 76 Serratia plasmids were sequenced, resulting in the identification of four additional tc variants. All Serratia tc variants were found to be colocated with a conserved type 1 sef fimbrial‐like operon, indicating a conserved sef‐tc genetic island not observed outside of the Serratia genus. The conserved co‐location of the fimbrial and tc genes suggests the fimbriae somehow contribute to the lifestyle of Tc‐producing cells. Expression of the sef operon in a fim‐null Escherichia coli strain revealed fimbriae presence while a constructed sef‐deficient mutant showed no reduction of virulence or host colonization. Although no detectable contribution of Sef to amber disease in C. giveni was observed, the Sef adhesin sequences clustered similarly to the Serratia species encoding it, suggesting Sef has a species‐specific function.

Abstract Introduction Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology. Summary Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.

Introduction: Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology. Summary: Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OVCA) is one of the most fatal gynecologic malignancies with most cases detected in late stages. High mortality rates are due, in part, to the lack of an effective early detection test. Tumor development and progression are associated with an increase in the expression of tissue proteins and/or their release into circulation. These proteins may offer potential markers for the early detection of OVCA. Nucleolin, a nuclear protein, is one such marker. This pilot study examined whether the tissue expression of nucleolin and its serum levels change in association with OVCA development and progression by using archived clinical samples and the laying hen model of spontaneous OVCA. Nucleolin was found to be highly expressed in ovaries and fimbriae with tumors and in serum levels compared to those without OVCA. This study also found that tumor-associated serum levels of nucleolin increase even before the tumor forms a detectable solid mass in the ovary or fimbria, suggesting that nucleolin may be involved in malignant transformation. A smaller sample size is a limitation of this study; however, it will lay the foundation for clinical studies with larger cohorts to examine the efficacy of nucleolin as a potential serum marker for the early detection of OVCA. Objective: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. Methods: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). Results: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. Conclusion: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer is one of the major reasons of mortality in women due to gynaecological malignancies. The origin of ovarian carcinomas was considered to be de novo previously. But recent studies have shown that the type II ovarian carcinomas, majority constituting of High Grade Serous Carcinomas (HGSCs) originate from the fimbrial end of the fallopian tubes. Aim: To establish an association of epithelial changes of fallopian tube with epithelial neoplasms of ovary in light of p53 expression. Materials and Methods: An observational, descriptive, crosssectional study was done in the Department of Pathology in a tertiary care centre of Eastern India for a period of 18 months from July 2019 to December 2020. Informed written consent was taken from all patients prior to the study. The epithelial ovarian neoplasms and fimbrial ends of the fallopian tubes using Sectioning and Extensively Examining the FIMbrial (SEE-FIM) end technique were submitted in 51 cases. The sections were stained with Haematoxylin and Eosin (H&E) and p53 tumour marker. The obtained results were tabulated and data analysis was done using Chi-square test and Fisher’s-exact test with the help of statistical software International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) version 25.0. A p-value of

Fimbrial adhesins promote bacterial adherence and biofilm formation. Sequencing of avian pathogenic Escherichia coli (APEC) strain QT598 identified new fimbriae belonging to the π group, which we named PL (P-like) fimbriae since the genetic organization and sequence are similar to those of P and related fimbriae. Genes encoding PL fimbriae located on IncF plasmids are present in diverse E. coli isolates from poultry, human systemic infections, and other sources. As with P fimbriae, PL fimbriae exhibit divergence in adhesin-encoding genes and could be divided into 5 classes based on sequence differences in the PlfG adhesin. plf genes from two predominant PlfG adhesin classes, PlfG class I (PlfGI) and PlfGII, were cloned. PL fimbriae were visualized by electron microscopy, associated with increased biofilm, demonstrated distinct hemagglutination profiles, and promoted adherence to human bladder and kidney epithelial cells. The genes encoding hybrid fimbriae were comprised of genes from plfQT598, wherein plfG was replaced by papG; the adhesin-encoding genes were also functional and mediated adherence to epithelial cells, demonstrating compatibility between the components of these two types of fimbriae. Deletion of plf genes did not reduce colonization of the mouse urinary tract in a single-strain infection model. In contrast, loss of plf genes significantly reduced competitive colonization in the mouse kidneys. Furthermore, plf gene expression was increased over 40-fold in the bladder compared to during in vitro culture. Overall, PL fimbriae represent a new group of fimbriae demonstrating both functional differences from and similarities to P fimbriae, which mediated adherence to host cells and improved competitive colonization of the mouse kidney. [ABSTRACT FROM AUTHOR]

Background: One of the few remaining important issues in urological and gynaecological surgery relates to fistulas between the urinary tract and the vagina. Vesicovaginal fistula (VVF) and ureterovaginal fistulas (UVF) are defined as abnormal connections between the urinary tract, on the one side, and the female genital system, on the other. Case Presentation: This study is about an unreported and undescribed case of 24 year old female who presented with the complaints of continuous urinary incontinence for 18 months following total abdominal hysterectomy. Preoperative cystoscopy and vaginal/speculum findings revealed a papillary frond like mass protruding intravesically from VVF site which was free from the edges of fistulous opening all around. Also, left ureteric orifice was not visualized. On exploration, there was evidence of intravesical herniation of right tubal fimbria through the common opening of VVF and left UVF near left vaginal vault apex mimicking a bladder mass presenting with continuous incontinence for 18 months. Modified O' Conners VVF repair with left ureteric reimplantation was done. The postoperative period was uneventful with patient having no incontinence. Conclusion: It seems that surgical resection of ovarian cyst with VVF and UVF repair is the definitive treatment and histopathological examination is essential to exclude malignant transformation. [ABSTRACT FROM AUTHOR]

Abstract Escherichia coli is generally used as model bacteria to define microbial cell factories for many products and to investigate regulation mechanisms. E. coli exhibits phospholipids, lipopolysaccharides, colanic acid, flagella and type I fimbriae on the outer membrane which is a self-protective barrier and closely related to cellular morphology, growth, phenotypes and stress adaptation. However, these outer membrane associated molecules could also lead to potential contamination and insecurity for fermentation products and consume lots of nutrients and energy sources. Therefore, understanding critical insights of these membrane associated molecules is necessary for building better microbial producers. Here the biosynthesis, function, influences, and current membrane engineering applications of these outer membrane associated molecules were reviewed from the perspective of synthetic biology, and the potential and effective engineering strategies on the outer membrane to improve fermentation features for microbial cell factories were suggested.

Objective: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. Methods: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). Results: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. Conclusion: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC.

Introduction: Ovarian cancer is one of the major reasons of mortality in women due to gynaecological malignancies. The origin of ovarian carcinomas was considered to be de novo previously. But recent studies have shown that the type II ovarian carcinomas, majority constituting of High Grade Serous Carcinomas (HGSCs) originate from the fimbrial end of the fallopian tubes. Aim: To establish an association of epithelial changes of fallopian tube with epithelial neoplasms of ovary in light of p53 expression. Materials and Methods: An observational, descriptive, crosssectional study was done in the Department of Pathology in a tertiary care centre of Eastern India for a period of 18 months from July 2019 to December 2020. Approval from an Institutional Review Board (IRB) was obtained at the initiation of the study. All patients signed informed written consent. The epithelial ovarian neoplasms and fimbrial ends of the fallopian tubes using Sectioning and Extensively Examining the FIMbrial (SEE-FIM) end technique were submitted in 51 cases. The sections were stained with Haematoxylin and Eosin (H&E) and p53 tumour marker. The obtained results were tabulated and data analysis was done using Chi-square test and Fischer-exact test with the help of statistical software International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) 25.0. A p-value of <0.05 was considered statistically significant. Results: On histopathological examination, 84.31% (43/51) cases were found to be Serous Tumours of the ovary, out of which 54.9% (28/51) cases showed histological features of HGSCs, 100% of these HGSCs were p53 positive. Thirteen cases (46.42%) of fimbrial ends of HGSCs showed nuclear atypia, pleomorphism and stratification and p53 positivity were categorised as Serous Tubal Intra Epithelial Carcinomas (STIC). The 10 cases (10/28=35.71%) fimbrial ends which showed p53 positive in minimum of 12 cells in the fimbrial ends were labelled as 'p53 signatures'. The remaining five cases didn't show any significant finding. Conclusion: Overall, the fimbrial end of the fallopian tube could be considered as the origin of these HGSCs and these lesions are precancerous in nature. [ABSTRACT FROM AUTHOR]

Poly-3-hydroxybutyrate (PHB) is an environmentally friendly polymer and can be produced in Escherichia coli cells after overexpression of the heterologous gene cluster phaCAB. The biosynthesis of the outer membrane (OM) consumes many nutrients and influences cell morphology. Here, we engineered the OM by disrupting all gene clusters relevant to the polysaccharide portion of lipopolysaccharide (LPS), colanic acid (CA), flagella, and/or fimbria in E. coli W3110. All these disruptions benefited PHB production. Especially, disrupting all these OM components increased the PHB content to 83.0 wt% (PHB content percentage of dry cell weight), while the wild-type control produced only 1.5 wt% PHB. The increase was mainly due to the LPS truncation to Kdo2 (3-deoxy-D-manno-octulosonic acid)-lipid A, which resulted in 82.0 wt% PHB with a 25-fold larger cell volume, and disrupting CA resulted in 57.8 wt% PHB. In addition, disrupting LPS facilitated advantageous fermentation features, including 69.1% less acetate, a 550% higher percentage of autoaggregated cells among the total culture cells, 69.1% less biofilm, and a higher broken cell ratio. Further detailed mechanism investigations showed that disrupting LPS caused global changes in envelope and cellular metabolism: (i) a sharp decrease in flagella, fimbria, and secretions; (ii) more elastic cells; (iii) much greater carbon flux toward acetyl coenzyme A (acetyl-CoA) and supply of cofactors, including NADP, NAD, and ATP; and (iv) a decrease in by-product acids but increase in g-aminobutyric acid by activating s E factor. Disrupting CA, flagella, and fimbria also improved the levels of acetyl-CoA and cofactors. The results indicate that engineering the OM is an effective strategy to enhance PHB production and highlight the applicability of OM engineering to increase microbial cell factory performance. [ABSTRACT FROM AUTHOR]

Purpose: Temporal lobe epilepsy is associated with tissue abnormalities of several gray and white matter structures that are reproduced in animal models. Few longitudinal studies have focused on the identification of structural differences during epileptogenesis. The diffusion tensor model is a useful tool for evaluating cell death, gliosis, and axonal plasticity in epileptic subjects. This study aimed to evaluate temporal tissue changes after experimental status epilepticus in an animal model of chronic temporal lobe epilepsy.Methods: Systemic pilocarpine-induced status epilepticus in adult Sprague-Dawley rats. Animals were scanned using diffusion tensor imaging (DTI) at three time points: prior to status epilepticus, and 24 and 64 days post-induction (early and late chronic, respectively). Fractional anisotropy, apparent diffusion coefficient, axial diffusivity (D║), and radial diffusivity (D┴) were evaluated in white (fimbria, cingulum, corpus callosum, and internal capsule) and gray (dorsal hippocampus, dentate gyrus, and CA3) matter regions for the three time points. Histological assessment of neurodegeneration in Klüver-Barrera preparations from the same animals was performed.Results: Significantly reduced volume of dorsal hippocampus and fimbria of the epileptic animals was observed already at 24 days post-status epilepticus. Progressive changes of DTI parameters in both the white and gray matter structures of the experimental group were also observed. Stained sections confirmed such alterations.Conclusion: Our study revealed time-dependent diffusion changes in gray and white matter structures after pilocarpine-induced status epilepticus. The characterization of these alterations over time may be potential imaging markers for epileptogenesis. [ABSTRACT FROM AUTHOR]

Background: Information about the prevalence of fallopian tube pathology in the early stages of endometriosis is scarce. The aim of our study was to examine the association between genital endometriosis and the lengths of fallopian tubes in infertile women. Settings and Design: retrospective cohort study. Methods: We studied 651 infertile patients in the 20–40 year age group, who visited a Reproductive Clinic for treatment between 2012–2018. After laparoscopy, endometriosis (detected by histomorphology) was indicated in 472 cases and absent in 179 cases. The length of the fallopian tubes was estimated in 193 primary infertile women with endometriosis. We excluded patients from the study who had surgical intervention on their tubes. Appearance of tubes and fimbriae was assessed in 177 patients without endometriosis and in 461 patients with endometriosis. Results: The proportion of women with shorter (12 cm) left fallopian tubes was significantly higher in the group of patients without endometriosis. Correlation analysis showed significant positive correlations of endometriosis with: a short (12 cm) left fallopian tube-r = –0.596** (p < 0.001); Conclusions: Infertile women with minimal or mild endometriosis have been shown to have anatomical and structural changes in the fallopian tubes and fimbriae compared to those without endometriosis. The presence of genital endometriosis (I;II stage) maybe associated with shorter fallopian tubes.

Escherichia coli is generally used as model bacteria to define microbial cell factories for many products and to investigate regulation mechanisms. E. coli exhibits phospholipids, lipopolysaccharides, colanic acid, flagella and type I fimbriae on the outer membrane which is a self-protective barrier and closely related to cellular morphology, growth, phenotypes and stress adaptation. However, these outer membrane associated molecules could also lead to potential contamination and insecurity for fermentation products and consume lots of nutrients and energy sources. Therefore, understanding critical insights of these membrane associated molecules is necessary for building better microbial producers. Here the biosynthesis, function, influences, and current membrane engineering applications of these outer membrane associated molecules were reviewed from the perspective of synthetic biology, and the potential and effective engineering strategies on the outer membrane to improve fermentation features for microbial cell factories were suggested. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) strains producing K88 (F4) or F18 fimbriae and enterotoxins are the predominant cause of pig post-weaning diarrhea (PWD). We recently identified neutralizing epitopes of fimbriae K88 and F18, heat-labile toxin (LT), heat26 stable toxin type I (STa) and type II (STb), and Shiga toxin 2e (Stx2e). In this study, we explored novel epitope- and structure-based vaccinology platform multiepitope-fusion-antigen (MEFA) for PWD vaccine development. By using an epitope-substitution LT toxoid, which lacks enterotoxicity, but retains immunogenicity, as the backbone to present neutralizing epitopes of two ETEC fimbriae and four toxins, we generated PWD fimbria-toxin MEFA to mimic epitope native antigenicity. We then examined MEFA protein immunogenicity and evaluated MEFA application in PWD vaccine development. Mice subcutaneously immunized with PWD MEFA protein developed strong IgG responses to K88, F18, LT and STb and moderate responses to toxins Stx2e and STa. Importantly, MEFA-induced antibodies inhibited adherence of K88-fimbrial or F18-fimbrial bacteria to pig intestinal cells and also neutralized LT, STa, STb and Stx2e toxicity. These results indicated that PWD fimbria-toxin MEFA induced neutralizing antibodies against unprecedently two fimbriae and four toxins, and strongly suggested a potential application of this MEFA protein in developing a broadly protective PWD vaccine. [ABSTRACT FROM AUTHOR]

In this study, we sought to identify alterations of hippocampal shape and subfield volumes in a relatively large sample of medication‐free obsessive–compulsive disorder (OCD) patients without comorbid depression. 3D T1‐weighted Magnetic Resonance Imaging scans were collected from 81 medication‐free OCD patients and 95 age‐ and sex‐matched healthy controls (HC). Total hippocampal volume and volume of eight bilateral subfields were measured using FreeSurfer software. Subregional shape deformity was examined via FSL software. Volumetric and shape differences between groups and correlations with OCD symptoms were examined. The volume of right hippocampus was significantly reduced in OCD patients (p =.001, η2 = 0.065). Follow‐up analysis of right hemisphere subfields showed reduced volume in right subiculum (p < .001, η2 = 0.081), presubiculum (p < .001, η2 = 0.125), CA2/3 (p =.001, η2 = 0.06), and hippocampal tail (p < 0.001, η2 = 0.105), while the volume of right fimbria was increased (p =.001, η2 = 0.058). Shape analysis revealed a bilateral outward bending in the hippocampal body related to a lateral displacement of hippocampus from the body to the tail. Symptom severity was correlated with volumes of presubiculum (with compulsions, r = −0.25, p =.024) and fimbria (with obsessions, r = −0.28, p =.012), and with the lateral shift of middle and posterior hippocampus (with obsessions). Alterations across hippocampal subfields and overall shape may contribute to the distinctive cognitive and affective abnormalities associated with OCD. [ABSTRACT FROM AUTHOR]

Background: Escherichia coli (E. coli) is the major cause of urinary tract infections (UTIs) in hospital settings. Attachment to the target is the essential step to colonization of this organism in human host. S and A fimbriae are important virulence factors causing urinary tract infection in uropathogenic E. coli strains. Objective: To determine the frequency of S and A fimbriae encoding genes in uropathogenic E. coli isolated from patients admitted in teaching hospitals of Qazvin. Methods: In this descriptive study, 126 E. coli isolates were collected from urine samples between 2012 and 2013. All isolates were identified using standard laboratory techniques and further evaluated for the frequency of sfa and afa genes using PCR and sequencing methods. Findings: In total, 37 (29.4%) and 13 (10.3%) isolates were positive for the presence of sfa and afa genes, respectively. The afa and sfa-positive isolates were mostly collected from patients admitted in intensive care unit (5 isolates, 4%) and internal medicine (23 isolates, 18.3%) wards, respectively. Conclusion: The findings showed a considerable rate of sfa and afa virulence factors in urinary E. coli isolates. According to clinical importance of this virulence factors in establishment and progress of urinary tract infection, using useful treatment strategy is essential for eradicating of this pathogen in studied hospitals.

Periodontal disease is a significant problem in companion animals such as dogs and cats. However, there is little information available about fimbriae association of periodontal disease in companion animals. In this study, we have purified and characterized a fimbriae from Porphyromonas salivosa ATCC 49407. The molecular mass of this protein was approximately 60-kDa, as estimated by SDS-PAGE. Immunogold electron microscopy revealed that anti-60-kDa fimbrial serum bound to fimbria on the cell surface of P. salivosa ATCC 49407. However, fimbriae of P. gingivalis and P. gulae were not labeled with the same antibody. Immunoelectron-microscopic studies and immunoblot analysis revealed that antigenicity and molecular weight were distinct from previously reported Porphyromonas fimbrial proteins. The amino acid sequence of the N-terminal 15 residues of the 60-kDa fimbrillin protein revealed only 3 of 15 residues identical to other Porphyromonas species fimbrillin proteins. Thus, the N-terminal amino acid sequence of the 60-kDa fimbrillin protein of P. salivosa clearly differed from previously reported fimbrillin proteins. The level of adherence of the P. salivosa was 1.81%. It was confirmed that P. salivosa can adheres to human cells. These results suggest that the 60-kDa fimbriae of P. salivosa ATCC 49407 is a new type of fimbria and may have an important factor in the adherence host cells. We suggest that the surface structure of P. salivosa may have a role in the colonization of this organism in periodontal pockets in companion animals. [ABSTRACT FROM AUTHOR]

Abstract A recent paradigm shift in ovarian cancer research is the finding that many ovarian cancers may originate from fallopian tube epithelial (FTE) cells. As tissue stem and progenitor cells often serve as cells of origin of cancer, a better understanding of FTE stem/progenitor cells and how they become transformed is essential for early detection and prevention of ovarian cancer. To facilitate study of FTE stem/progenitor cells in model systems, we established an organoid culture system for mouse FTE cells. We find that EPCAM+ mouse FTE cells can be stably cultured long-term under a minimal condition of activated EGF signaling and suppressed TGFbeta signaling. We show that both Notch and Wnt signaling are required for growth of FTE cells in organoids, and further activation of Wnt signaling supports their maturation toward the ciliated cell lineage. Lastly, by analyzing the frequency of organoid-forming cells in different portions of the fallopian tube (FT), we find that the distal portion of the FT, which includes the fimbria, is enriched with organoid-forming FTE stem cells. Highlights • Mouse fallopian tube epithelial cells can be stably cultured long-term as organoids. • Long-term culture only requires activated EGF and suppressed TGFbeta signaling. • Both Notch and Wnt pathways play key roles in these organoids. • Organoid-forming fallopian tube stem cells are enriched toward the fimbrial portion. [ABSTRACT FROM AUTHOR]

Aim. Study adhesive activity of enterobacteria in the model of hemagglutination reaction with animal and avian erythrocytes and clarify structures responsible for adhesion in enterobacteria. Materials and methods. 58 cultures ofenterobacteria were used, ofwhich: 21 Escherichia coli strains, 13 Citrobacter spp., 11 Morganella morganii, 9 Proteus spp., 4 Hafnia alvei. Erythrocytes of various animals and birds were used in hemagglutination reaction. Electron-microscopical studies were carried out in JEM-100B (Japan) electron microscope. Results. Use of avian erythrocytes as a target of adhesion determination, compared with animal erythrocytes, has shown that bacteria can cause D-mannose-sensitive hemagglutination reaction, linked with the presence of110 - 420 nm long and 5.0 - 5.4 nm wide cilia in the microorganisms. Conclusion. Adhesion of enterobacteria was shown to be a complex process, depending on the presence of certain fimbrial structures, use of those results in specific interaction of the microbe with certain host cell receptors. Avian erythrocytes are a model target cells

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.

Mucinous adenocarcinoma of the fallopian tube is exceptionally rare and the detailed clinicopathologic features of these tumors have not yet been reported in English literature. Here we report a moderately differentiated mucinous adenocarcinoma arising in the tubal fimbria in a 70-year-old woman. Patient had a history of cholecystectomy for gallstones and gastric banding who presented with gastrointestinal discomfort and was found to have a large adnexal mass on imaging studies. Serum CA-125 was moderately elevated. Recent mammography, upper endoscopy and colonoscopy were completely normal. She underwent surgical staging for the adnexal mass. Frozen section and final pathology diagnosis revealed moderately differentiated adenocarcinoma arising in the left fimbria. Carcinoma had spread to the ipsilateral ovary and pelvic soft tissue at the time of her presentation. Tumor was strongly immunoreactive to CK7 and CEA, and was negative for CK20, CDX-2, PAX-8, WT-1, p16, ER, and vimentin. TP53 showed wild-type phenotype by immunohistochemistry. Molecular studies showed no mutation in codon 12 and 13 of the k-ras gene, and no mutation was detected in the BRAF and EGFR genes. In addition, the non-tumorous fimbria epithelium showed a spectrum of mucinous alterations with variable nuclear atypia: cytologically bland areas that were reminiscent of mucinous metaplasia were positive for p53 and showed minimal proliferation as assessed by Ki-67, and cytologically atypical stratified mucinous epithelium that was positive for p53 and Ki-67. The patient received 3 cycles of Folfox and was regularly followed at a 3–6 month interval. Her carcinoma recurred in abdomen at 32 months post surgery. After excluding the possibility of an extra-gynecologic tract primary through extensive clinical investigations and post-surgical follow-up, we concluded that this tumor most likely represented a mucinous adenocarcinoma of tubal origin.

Enterotoxigenic Escherichia coli (ETEC) K88 (F4) is a worldwide cause of severe diarrhoea in the offspring of some animal species such as weaned pigs. Preventing ETEC K88 (F4) attaching to the small intestine by natural feed ingredients interfering with its fimbria-receptor recognition could be an alternative method to reduce diarrhoea occurrence. The purpose of this study is to evaluate the ability of different common ingredients in the formulation of pig diets, and particularly different kinds of cereal brans, to attach ETEC K88 (F4) (adhesion test, AT) and to block its attaching to intestinal epithelial cells (IPEC-J2) (blocking test, BT) in vitro . For the feed ingredients, wheat, corn, oats, barley, rye, extruded full-fat soybean meal, soybean meal, as well as sweet whey powder, all demonstrated a clear affinity to attach ETEC K88 (F4) ( P < 0.05). Regarding rye, oats ( P < 0.01) and also wheat ( P  = 0.05), all of them could also reduce ETEC K88 (F4) adhesion to IPEC-J2 cells. Among differently tested cereal brans, wheat bran, spelt bran, kamut bran, rye bran, oat bran and rice bran all demonstrated an ability to attach ETEC K88 (F4) ( P < 0.001) and all of them were able to reduce ETEC K88 (F4) attachment to IPEC-J2 cells ( P < 0.001), except rice bran. Results from these experiments highlight the functional properties of some common feed ingredients like rye, oats and wheat, in addition to their bran to prevent the adhesion of ETEC K88 (F4) to the intestinal epithelium. The properties of these ingredients could be considered as an additional criteria, together to their nutritive value, in the formulation of diets to prevent the appearance of post-weaning diarrhoea. [ABSTRACT FROM AUTHOR]

Abstract: Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra‐hippocampal white matter structure, in relation to the progression of well‐accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid‐β 1‐42 (Aβ) and total‐tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple‐sibling familial history of AD. Apolipoprotein (APOE) ɛ4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated‐tau (p‐tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra‐hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment. [ABSTRACT FROM AUTHOR]

Background: One of the most frequent health problems in the swine industry is the post-weaning diarrhea in nursery pigs, which leads to significant losses due to weight loss, dehydration, cost of medication and mortality. Escherichia coli (E. coli) is one of the main bacterial agents of the post-weaning diarrhea. To investigate the possibility of enterotoxigenic E. coli (ETEC) transmission through drinking water to nursery piglets, the objective of this study was to isolate, characterize by virulence factors, and compare the antimicrobial resistance profiles of E. coli from drinking water samples in nurseries and from rectal swabs of their piglets presenting post-weaning colibacillosis. Materials, Methods & Results: Fifteen rectal swabs from diarrheic piglets in their first three weeks after weaning and one water sample were collected from each of ten nurseries located in Rio Grande do Sul State, south of Brazil. After enrichment with a commercial broth medium, water samples were cultured in blood agar, as well as the rectal swab samples, and the characteristic colonies were identified by standard biochemical analysis. Following isolation and identification of E. coli, the colonies from water samples and their corresponding piglets' samples were characterized by multiplex PCR in order to determine specific ETEC fimbria and toxin genes. Finally, all E. coli isolates were submitted to antimicrobial susceptibility testing. Virulence factors and antimicrobial sensitivity could then be compared between water and piglets' samples. The difference in the antimicrobial resistance frequency for each of the sample groups were compared using the multi comparison test. E. coli was isolated in four out of the ten water samples, although none of the water samples presented ETEC virulence factors. From 60 rectal swab samples (15 from each of the four positive farms with E. coli isolated from water samples), 21 E. coli were isolated and seven demonstrated characteristic ETEC virulence factors. The fimbriae exhibited in higher frequency were F18 (62.5%) and F4 (25%) and the toxins were STb (100%) and STaP (75%). E. coli isolated from water samples presented higher resistance to the antimicrobials apramycin, florfenicol, lincomycin, lincomycin+spectinomycin, oxytetracycline, and sulfamethoxazole+trimethoprim; it did not present resistance to colistin and fosfomycin. The seven ETEC from rectal swab samples presented a higher resistance to lincomycin, and lower resistance frequency to fosfomycin. The other 14 E. coli non-ETEC from rectal swab samples presented a higher resistance to florfenicol and no resistance to colistin. Discussion: Enterotoxigenic E. coli is an important agent causing post-weaning colibacillosis, although, differently from other studies, this experiment did not find the agent in most of the sampled animals. In contrast to other authors, ETEC was not found in water, as the development of its virulence factors may depend on conditions presented exclusively in the animal. By the results we can conclude that, although E. coli was isolated from the drinking water, it was not a significant mechanism for nursery piglets' infection with ETEC in this experiment. The samples analyzed presented a wide range of resistance to different antimicrobials, including multi-resistance. In some cases, E. coli found in water presented different antimicrobial profile from the bacterium found in the rectal swab samples. Enterotoxigenic E. coli was susceptible to fosfomycin and its use may represent a prudent antimicrobial choice to the swine industry. [ABSTRACT FROM AUTHOR]

Background: One of the most frequent health problems in the swine industry is the post-weaning diarrhea in nursery pigs, which leads to significant losses due to weight loss, dehydration, cost of medication and mortality. Escherichia coli (E. coli) is one of the main bacterial agents of the post-weaning diarrhea. To investigate the possibility of enterotoxigenic E. coli (ETEC) transmission through drinking water to nursery piglets, the objective of this study was to isolate, characterize by virulence factors, and compare the antimicrobial resistance profiles of E. coli from drinking water samples in nurseries and from rectal swabs of their piglets presenting post-weaning colibacillosis. Materials, Methods & Results: Fifteen rectal swabs from diarrheic piglets in their first three weeks after weaning and one water sample were collected from each of ten nurseries located in Rio Grande do Sul State, south of Brazil. After enrichment with a commercial broth medium, water samples were cultured in blood agar, as well as the rectal swab samples, and the characteristic colonies were identified by standard biochemical analysis. Following isolation and identification of E. coli, the colonies from water samples and their corresponding piglets' samples were characterized by multiplex PCR in order to determine specific ETEC fimbria and toxin genes. Finally, all E. coli isolates were submitted to antimicrobial susceptibility testing. Virulence factors and antimicrobial sensitivity could then be compared between water and piglets' samples. The difference in the antimicrobial resistance frequency for each of the sample groups were compared using the multi comparison test. E. coli was isolated in four out of the ten water samples, although none of the water samples presented ETEC virulence factors. From 60 rectal swab samples (15 from each of the four positive farms with E. coli isolated from water samples), 21 E. coli were isolated and seven demonstrated characteristic ETEC virulence factors. The fimbriae exhibited in higher frequency were F18 (62.5%) and F4 (25%) and the toxins were STb (100%) and STaP (75%). E. coli isolated from water samples presented higher resistance to the antimicrobials apramycin, florfenicol, lincomycin, lincomycin+spectinomycin, oxytetracycline, and sulfamethoxazole+trimethoprim; it did not present resistance to colistin and fosfomycin. The seven ETEC from rectal swab samples presented a higher resistance to lincomycin, and lower resistance frequency to fosfomycin. The other 14 E. coli non-ETEC from rectal swab samples presented a higher resistance to florfenicol and no resistance to colistin. Discussion: Enterotoxigenic E. coli is an important agent causing post-weaning colibacillosis, although, differently from other studies, this experiment did not find the agent in most of the sampled animals. In contrast to other authors, ETEC was not found in water, as the development of its virulence factors may depend on conditions presented exclusively in the animal. By the results we can conclude that, although E. coli was isolated from the drinking water, it was not a significant mechanism for nursery piglets' infection with ETEC in this experiment. The samples analyzed presented a wide range of resistance to different antimicrobials, including multi-resistance. In some cases, E. coli found in water presented different antimicrobial profile from the bacterium found in the rectal swab samples. Enterotoxigenic E. coli was susceptible to fosfomycin and its use may represent a prudent antimicrobial choice to the swine industry. [ABSTRACT FROM AUTHOR]