Miracle-dz/UniFAR-FTUs huggingface dataset:
INTESTINAL EN RATAS CON HIPERSENSIBILIDAD Y MECANISMOS NEUROENDOCRINOS REGULADORES DE LA FUNCIÓN MASTOCITARIA

Several studies demonstrate that intestinal mucosal mast cells (IMMC) are modulated by nervous reflexes as well as by intraluminal content. We recently demonstrated that peptones, such as ovalbumin hydrolysate (OVH), induce the release of rat mast cell protease II (RMCP II), indicating IMMC degranulation. The response is due to complex neuroendocrine reflexes. Somatostatin (SS) and its analogues have been used as potential treatments for inflammation in other body systems with contradictory results. The aim of this study was to evaluate if somatostatin could contribute to the reduction of intestinal mucosal mast cell degranulation. Anesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Somatostatin significantly decreased RMCP II concentration in both nonstimulated conditions and after ovalbumin hydrolysate perfusion. However, when somatostatin was given previously to OVH, the peptone still induced a slight increase of RMCP II. Similar effects were observed in animals previously treated with capsaicin. These protocols were repeated in animals infected with Trichinella spiralis, which induces mucosal mast cell hyperplasia. In these cases, somatostatin blocked the effect of OVH, thus, preventing an increase in RMCP II concentration. Fresh frozen tissue sections from the duodenum were processed in an attempt to demonstrate the presence of SS receptors in mast cells using immunofluorescence and Fluo-peptide labeling techniques. Confocal images from duodenum specimens demonstrate the existence of SS receptors in positive cells for RMCP II. Taken together, these results indicate that somatostatin diminishes mast cell activity and in consequence could prevent the intestinal responses to mast cell hyperplasia. D 2002 Elsevier Science B.V. All rights reserved.
Production of Fructooligosaccharides using Free-whole-cell Biotransformation by Aspergillus niger CGMCC No.6640

Fructooligosaccharides(FOS) have received particular interest because of their excellent biological and functional properties for using as a prebiotic compound.The strain Aspergillus niger CGMCC No.6640 with independent intellectual property rights was found capable of producing FOS using sucrose as the substrate.To produce FOS using free-whole-cell biotransformation by A.niger 6640,the effects of production parameters on the biotransformation of sucrose were investigated by HPLC with the column of Rezex RCM-Monosaccharife Cat.The catalysate concentration of the Nystose(or 1F-Fructofuranosylnystose),kestose,sucrose,glucose and fructose were simultaneously detected,and their retention time was 8.403 min,8.853 min,9.705 min,11.473 min and 14.683 min,respectively.The free-whole-cell concentration and substrate concentration positively affected the maximum FOS yield.However CaCl2 concentration negatively affected the FOS yield.The free-whole-cell concentration,the initial reaction pH,the temperature for catalysis,biotransformation time and sucrose concentration were 60 g/L,7.0,33 ℃,40 h and 600 g/L,respectively.Under the optimal conditions were as follows,the FOS contents reached 314.60 g/L.In summary,the free-whole-cell biocatalyst of A.niger 6640 can effectively produce FOS indicating a potential for industrial production.
A Laboratory-Specific Scaling Factor to Predict the In Vivo Human Clearance of Aldehyde Oxidase Substrates

Aldehyde oxidase (AO) efficiently metabolizes a range of compounds with N-containing heterocyclic aromatic rings and/or aldehydes. The limited knowledge of AO activity and abundance (in vitro and in vivo) has led to poor prediction of in vivo systemic clearance (CL) using in vitro–to–in vivo extrapolation approaches, which for drugs in development can lead to their discontinuation. We aimed to identify appropriate scaling factors to predict AO CL of future new chemical entities (NCEs). The metabolism of six AO substrates was measured in human liver cytosol (HLC) and S9 fractions. Measured blood-to-plasma ratios and free fractions (in the in vitro system and in plasma) were used to develop physiologically based pharmacokinetic models for each compound. The impact of extrahepatic metabolism was explored, and the intrinsic clearance required to recover in vivo profiles was estimated and compared with in vitro measurements. Using HLC data and assuming only hepatic metabolism, a systematic underprediction of clearance was observed (average fold underprediction was 3.8). Adding extrahepatic metabolism improved the accuracy of the results (average fold error of 1.9). A workflow for predicting metabolism of an NCE by AO is proposed, and an empirical (laboratory-specific) scaling factor of three on the predicted intravenous CL allows a reasonable prediction of the available clinical data. Alternatively, considering also extrahepatic metabolism, an scaling factor of 6.5 applied on the intrinsic clearance could be used. Future research should focus on the impact of the in vitro study designs and the contribution of extrahepatic metabolism to AO-mediated clearance to understand the mechanisms behind the systematic underprediction. SIGNIFICANCE STATEMENT This works describes the development of scaling factors to allow in vitro–in vivo extrapolation of the clearance of compounds by aldehyde oxidase metabolism in humans. In addition, physiologically based pharmacokinetic models were developed for each of the aldehyde oxidase substrate compounds investigated.
Global analysis of FSH‐regulated gene expression and histone modification in mouse granulosa cells

Follicle‐stimulating hormone (FSH) regulates ovarian follicular development through a specific gene expression program. We analyzed FSH‐regulated transcriptome and histone modification in granulosa cells during follicular development. We used super‐stimulated immature mice and collected granulosa cells before and 48 h after stimulation with equine chorionic gonadotropin (eCG). We profiled the transcriptome using RNA‐sequencing (N = 3/time‐point) and genome‐wide trimethylation of lysine 4 of histone H3 (H3K4me3; an active transcription marker) using chromatin immunoprecipitation and sequencing (ChIP‐Seq; N = 2/time‐point). Across the mouse genome, 14,583 genes had an associated H3K4me3 peak and 63–66% of these peaks were observed within ≤1 kb promoter region. There were 72 genes with differential H3K4me3 modification at 48 h eCG (absolute log fold change > 1; false discovery rate [FDR] < 0.05) relative to 0 h eCG. Transcriptome data analysis showed 1463 differentially expressed genes at 48 h eCG (absolute log fold change > 1; FDR < 0.05). Among the 20 genes with differential expression and altered H3K4me3 modification, Lhcgr had higher H3K4me3 abundance and expression, while Nrip2 had lower H3K4me3 abundance and expression. Using ChIP‐qPCR, we showed that FSH‐regulated expression of Lhcgr, Cyp19a1, Nppc, and Nrip2 through regulation of H3K4me3 at their respective promoters. Transcript isoform analysis using Kallisto‐Sleuth tool revealed 875 differentially expressed transcripts at 48 h eCG (b > 1; FDR < 0.05). Pathway analysis of RNA‐seq data demonstrated that TGF‐β signaling and steroidogenic pathways were regulated at 48 h eCG. Thus, FSH regulates gene expression in granulosa cells through multiple mechanisms namely altered H3K4me3 modification and inducing specific transcripts. These data form the basis for further studies investigating how these specific mechanisms regulate granulosa cell functions.
The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra‐ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye‐motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2water) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2water values were determined in 12 HC (aged 22‐65 years), 11 MG (aged 28‐71 years) and six GO (aged 28‐64 years) patients at 7 T using Dixon and multi‐echo spin‐echo sequences. The EOM were semi‐automatically 3D‐segmented by two independent observers. MANOVA and t‐tests were used to assess differences in FF, T2water and volume of EOM between groups (P < .05). Bland–Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was −0.7% (LoA: ±2.1%) for the different observers; the bias in FF was −0.3% (LoA: ±2.8%) and 0.03 cm3 (LoA: ± 0.36 cm3) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm3) and MG (0.8 ± 0.2 cm3) compared with HC (0.6 ± 0.2 cm3). The average T2water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.
Endpoint and Epitope-specific Antibody Responses as Correlates of Vaccine-mediated Protection of Mice against Ricin Toxin

The successful licensure of vaccines for biodefense is contingent upon the availability of well-established correlates of protection (CoP) in at least two animal species that can then be applied to humans, without the need to assess efficacy in the clinic. In this report we describe a multivariate model that combines pre-challenge serum antibody endpoint titers (EPT) and values derived from an epitope profiling immune-competition capture (EPICC) assay as a predictor in mice of vaccine-mediated immunity against ricin toxin (RT), a Category B biothreat. EPICC is a modified competition ELISA in which serum samples from vaccinated mice were assessed for their ability to inhibit the capture of soluble, biotinylated (b)-RT by a panel of immobilized monoclonal antibodies (mAbs) directed against four immunodominant toxin-neutralizing regions on the enzymatic A chain (RTA) of RT. In a test cohort of mice (n=40) vaccinated with suboptimal doses of the RTA subunit vaccine, RiVax®, we identified two mAbs, PB10 and SyH7, which had EPICC inhibition values in pre-challenge serum samples that correlated with survival following a challenge with 10 x LD50 of RT administered by intraperitoneal (IP) injection. Analysis of a larger cohort of mice (n=645) revealed that a multivariate model combining endpoint titers and an epitope-profiling immune-competition capture (EPICC) assay values for PB10 and SyH7 as predictive variables had significantly higher statistical power than any one of the independent variables alone. Establishing the correlates of vaccine-mediated protection in mice represents an important steppingstone in the development of RiVax® as a medical countermeasure under the United States Food and Drug Administration’s “Two Animal Rule. ”
Edinburgh Research Explorer Redefining the H-NS protein family: a diversity of specialized core and accessory forms exhibit hierarchical transcriptional network integration

H-NS is a nucleoid structuring protein and global repressor of virulence and horizontally-acquired genes in bacteria. H-NS can interact with itself or with homologous proteins, but protein family diversity and regulatory network overlap remain poorly de-ﬁned. Here, we present a comprehensive phylogenetic analysis that revealed deep-branching clades, dispelling the presumption that H-NS is the progeni-tor of varied molecular backups. Each clade is composed exclusively of either chromosome-encoded or plasmid-encoded proteins. On chromosomes, stpA and newly discovered hlpP are core genes in spe-ciﬁc genera, whereas hfp and newly discovered hlpCare sporadically distributed. Six clades of H-NS plasmid proteins (Hpp) exhibit ancient and dedicated associations with plasmids, including three clades with ﬁdelity for plasmid incompatibility groups H, F or X. A proliferation of H-NS homologs in Erwiniaceae includes the ﬁrst observation of potentially co-dependent H-NS forms. Conversely, the observed diversiﬁcation of oligomerization domains may facilitate stable co-existence of divergent homologs in a genome. Transcriptomic and proteomic analysis in Salmonella revealed regulatory crosstalk and hierarchical control of H-NS homologs. We also discovered that H-NS is both a repressor and activator of Salmonella Pathogenicity Island 1 gene expression, and both regulatory modes are restored by Sfh (HppH) in the absence of H-NS.
Impact of Homozygous C4A Deficiency on Clinical Presentation of Systemic Lupus Erythematosus.

OBJECTIVE To investigate the association of C4A null allele (C4AQ0) with systemic lupus erythematosus (SLE) and determine the clinical presentation of SLE in relation to C4A null allele. STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY Armed Forces Institute of Pathology (AFIP), Rawalpindi, Immunology Department, from December 2018 to December 2019. METHODOLOGY Patients referred to AFIP, who fulfilled American College of Rheumatology (ACR) criteria of 1997 for diagnosis of SLE were included in the study. Approval from the Institutional Ethical Review Board was taken. C4A and C4B null alleles were determined in 66 SLE patients and 40 age- and gender-matched healthy controls by polymerase chain reaction (PCR) using sequence-specific primers (PCR-SSP). Various clinical features and laboratory findings in the SLE patients were analysed in relation with C4A null allele. RESULTS The mean age of the study population was 30.56 ±10.08 years. C4A null allele was detected in 7 (10.6%) patients; whereas, C4B null allele was detected in only two (3%) patients. SLE patients with C4A null allele had increased incidence of arthritis (100%) and renal damage (85.7%); compared to those with normal C4A allele, 57.6% and 32%, respectively. Fisher's Exact test revealed strong association of C4A null allele with arthritis and renal damage, (p = 0.039 and 0.01, respectively). CONCLUSION Homozygous absence of C4A alleles was encountered in 10.6% of Pakistani patients of SLE and is closely related with clinical features of arthritis and renal damage. Knowledge of C4A null allele in SLE patients at diagnosis can predict disease course. Key Words: SLE, C4A null alleles, C4AQ0, Homozygous C4A deficiency.
Feeding Behavior and Food Habits of the Boat-billed Heron (Cochlearius cochlearius)

Boat-billed herons (Cochlearius c. ridgwayi) were observed with a night vision device as they fed nocturnally in a Pacific Guatemalan marsh. They used two basic heron/egret feeding techniques previously described for other species. No specialized feeding behaviors were observed that could be related uniquely to the expanded bill. Food taken by boat-bills was similar to that of black-crowned and yellow-crowned night herons (Nycticorax nycticorax and Nyctanassa violacea) feeding in the same marsh. Because of the limited information on Cochlearius, none of the existing hypotheses are adequate to explain the shape of the bill as a feeding adaptation, and only a previous observation of the bill as a display character provides a plausible explanation. THE FUNCTION of the oddly expanded bill of the boat-billed heron (Cochlearius cochlearius) has for years been assumed to be associated with some specialized feeding technique. Bock (1956) suggested that ". Cochlearius feeds in a manner different from that of other herons. A broad bill may be used as a scoop or may enable the bird to feed on smaller animal life. " More recently, Mock (1975) proposed a hypothetical "touch-feeding" technique specialized to exploit a seasonal abundance of mud-dwelling organisms. Some brief observations of feeding appear in the literature. In Nicaragua, Boavalius (fide Rendahl 1920) said they "waded about, picking up fishes with a surprising rapidity. " Wetmore (1965) reported that "they stand or walk in shallow ripples in the rivers, where they scoop at aquatic animals rather than spear at them in heron style. " Feeding behavior under an attempted simulation of natural conditions was described by Carpenter (1971). Sys,tematized field studies, of the boat-bill have only recently been made. Two studies at San Blas, Nayarit, Mexico provided the first details on the boat-bill's breeding biology (Dickerman and Juarez 1971) and breeding display repertoire (Mock 1976). The present paper records the first detailed observations of nocturnal feeding of boat-billed herons (subspecies Cochlearius c. ridgwayi Dickerman 1973) and includes a description and discussion of their food habits.
Proper Care and Feeding of Coccidioides: A Laboratorian's Guide to Cultivating the Dimorphic Stages of C. immitis and C. posadasii

Coccidioidomycosis (“Valley fever”) is caused by Coccidioides immitis and C. posadasii. These fungi are thermally dimorphic, cycling between mycelia and arthroconidia in the environment and converting into spherules and endospores within a host. Coccidioides can cause a broad spectrum of disease that can be difficult to treat. There has been a steady increase in disease, with an estimated 350,000 new infections per year in the United States. With the increase in disease and difficulty in treatment, there is an unmet need to increase research in basic biology and identify new treatments, diagnostics, and vaccine candidates. Here, we describe protocols required in any Coccidioides laboratory, such as growing, harvesting, and storing the different stages of this dimorphic fungal pathogen. © 2020 Wiley Periodicals LLC.
Management of incidental unruptured intracranial aneurysms

The widespread use of MR has led to the increasingly frequent diagnosis of unruptured incidental intracranial aneurysms. Most are small (<7 mm diameter) and will never rupture. Yet, their recognition causes much anxiety, and their optimal management remains controversial. This review addresses the difficulties in managing incidental unruptured saccular intracranial aneurysms. Note that our conclusions and recommendations do not apply to symptomatic unruptured aneurysms or to fusiform, dissecting, mycotic, traumatic and paediatric aneurysms, each of which has a different natural history.
Orthodontic treatment need and timing: Assessment of evolutive malocclusion conditions and associated risk factors.

AIM Orthodontic treatment need indexes are indispensable tools for collecting aepidemiological information, to define the need for clinical intervention on a graduated risk scale and to monitor the evolution of clinical conditions over time. The purpose of this research is to evaluate the prevalence of malocclusion and associated risk factors, and to compare the prevalence of malocclusion related to children's growth. Investigating the correlation between malocclusion and dental occlusion development is crucial to define orthodontic timing and the most suitable treatment modalities. MATERIALS AND METHODS A cross-sectional, multi-center, observational study was carried out throughout Italy: 4,422 patients aged between 2 and 13 years were visited. The patients were divided into two age groups: one composed of patients aged 2 -7 years, and one of children between 8 and 13 years of age. The prevalence data were classified according to the items of the Baby ROMA (first group, deciduous/early mixed dentition) and ROMA Index (second group, late mixed/permanent dentition). Pearson's Chi-square test was applied for the calculation of statistical significance in the comparison of prevalence data between the two age groups (P <0.05). RESULTS The need for orthodontic treatment among Italian children is high. In the sample aged between 2 and 7 years, the most frequent malocclusions are the moderate and severe open bite (23%), moderate and severe Class II (21.2%), deep bite (18.8%), cross bite (16.5%), Class III (7.7%), and crowding (5.1%). In the sample aged between 8 and 13 years the most frequent malocclusions are crowding (50.8 %), Class II (33.1%), deep bite (19.2%) crossbite (18.1%), Class III (9.1%), open bite (6.6%), facial or mandibular asymmetries (3.3%), and functional asymmetries (3.2%). It was found a statistically significant variation of the different malocclusion conditions according to age. CONCLUSION The study confirms that some risk factors occur during growth, and worsen the malocclusion. Therefore, it is important to reduce this risk of worsening by counteracting those factors with an early orthodontic intervention. Some malocclusions are less affected by environmental risk factors. In these case it would be better defer treatment until adolescence.
Diverse CBX family members as potential prognostic biomarkers in non‐small‐cell lung cancer

Chromobox (CBX) family members are vital epigenetic regulators that repress the transcription of target genes through chromatin modification. Several studies have investigated the role of CBX family members in cancer. However, the function and prognostic value of diverse CBX family members in non‐small‐cell lung cancer remain largely unknown. In this study, we reveal that CBX family members are overexpressed in non‐small‐cell lung cancer tissue compared with normal lung tissue, with the exception of CBX6. Kaplan–Meier analysis demonstrated that high expressions of CBX1 and CBX3 are correlated with overall survival, disease‐specific survival, disease‐free interval, and progression‐free interval for patients with lung adenocarcinoma (LUAD). Furthermore, regression model analysis suggests that CBX3 may be suitable as an independent prediction factor for overall survival and progression‐free interval in patients with LUAD. In addition, CBX3 mRNA expression was found to be associated with tumor diameter and lymph node metastasis. Gene enrichment analysis suggests that CBX3 is involved in the cell cycle and P53 signaling pathways. Aberrant expression of CBX3 in LUAD is correlated with DNA copy number alteration. In summary, our data imply that CBX3 plays an important role in the promotion of LUAD and may thus have potential as a prognostic biomarker and molecular therapeutic target for the disease.