Miracle-dz/UniFAR-FTUs huggingface dataset:
The Campylobacter jejuni Dps Homologue Is Important for In Vitro Biofilm Formation and Cecal Colonization of Poultry and May Serve as a Protective Antigen for Vaccination

ABSTRACT In this work, we investigated the Campylobacter jejuni dps (DNA binding protein from starved cells) gene for a role in biofilm formation and cecal colonization in poultry. In vitro biofilm formation assays were conducted with stationary-phase cells in cell culture plates under microaerophilic conditions. These studies demonstrated a significant (>50%) reduction in biofilm formation by the C. jejuni dps mutant compared to that by the wild-type strain. Studies in poultry also demonstrated the importance of the dps gene in host colonization by C. jejuni. Real-time PCR analysis of mRNA extracted from the cecal contents of poultry infected with wild-type C. jejuni indicated that the dps gene is upregulated 20-fold during poultry colonization. Cecal colonization was greater than 5 log CFU lower in chicks infected with the dps mutant than chicks infected with the wild-type C. jejuni strain. Moreover, the dps mutant failed to colonize 75% of the chicks following challenge with 105 CFU. Preliminary studies were conducted in chicks by parenteral vaccination with a recombinant Dps protein or through oral vaccination with a recombinant attenuated Salmonella enterica strain synthesizing the C. jejuni Dps protein. No reduction in C. jejuni was noted in chicks vaccinated with the parenteral recombinant protein, whereas, a 2.5-log-unit reduction of C. jejuni was achieved in chicks vaccinated with the attenuated Salmonella vector after homologous challenge. Taken together, this work demonstrated the importance of Dps for biofilm formation and poultry colonization, and the study also provides a basis for continued work using the Dps protein as a vaccine antigen when delivered through a Salmonella vaccine vector.
Emergence of the Permanent Teeth in Pima Indian Children

THE PROCESS of tooth emergence is traditionally a source of information on the status and progress of physiologic development. Concentrating on the applied aspects of the problem, authors of the studies in the literature are publishing for the practicing dentist, orthodontist, and forensic anthropometrist. The practitioner has found this material useful within broad limits in planning treatment and as a criterion of age. However, both the practitioner and the research worker would profit from a more detailed analysis of the patterns of dental eruption. Studies of the emergence of the teeth of the Pima Indians showed that replacement of the deciduous teeth with the permanent ones is for them a process which starts later and finishes earlier than in most other populations. These materials also permitted another view of the importance of the second premolar-second molar eruption sequence. Some authors have claimed that the second premolar followed by the second molar is an advanced trait and the reverse, that is, the second molar followed by the second premolar, is a primitive or ancestral sequence. The Pima material supports the rather recent work and discussions by Garn, Koski, and Lewis' that the so-called ancestral sequence is common in at least several modern populations. In approaching these and other problems it was found that the parameters, methods, types of studies, and the available data from previous publications had to be subjected to review.
Toward Ubiquitous Blood Pressure Monitoring via Pulse Transit Time: Theory and Practice

Ubiquitous blood pressure (BP) monitoring is needed to improve hypertension detection and control and is becoming feasible due to recent technological advances such as in wearable sensing. Pulse transit time (PTT) represents a well-known potential approach for ubiquitous BP monitoring. The goal of this review is to facilitate the achievement of reliable ubiquitous BP monitoring via PTT. We explain the conventional BP measurement methods and their limitations; present models to summarize the theory of the PTT-BP relationship; outline the approach while pinpointing the key challenges; overview the previous work toward putting the theory to practice; make suggestions for best practice and future research; and discuss realistic expectations for the approach.
Increased Cerebrospinal Fluid Dopamine and 3,4‐Dihydroxyphenylacetic Acid Levels in Huntington's Disease: Evidence for an Overactive Dopaminergic Brain Transmission

Abstract: Levels of dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 3‐methoxy‐4‐hydroxyphenylglycol (MHPG), and 5‐hydroxyindoleacetic acid (5‐HIAA) in the CSF of patients with Huntington's disease (HD) were measured by HPLC. CSF DA, DOPAC, and MHPG levels were found to be increased in HD patients. Levels of HVA, 5‐HIAA, and NA in the CSF of HD patients did not differ from those of controls. Changes in CSF DA and DOPAC levels were consistent with previous findings of increased DA tissue content in some brain areas of patients with HD. These results suggest that CSF DOPAC levels could be a more reliable index of over‐active dopaminergic brain systems in HD than CSF HVA levels.
Mitochondrial Transcription Factor B2 Is Essential for Metabolic Function in Drosophila melanogaster Development*

Characterization of the basal transcription machinery of mitochondrial DNA (mtDNA) is critical to understand mitochondrial pathophysiology. In mammalian in vitro systems, mtDNA transcription requires mtRNA polymerase, transcription factor A (TFAM), and either transcription factor B1 (TFB1M) or B2 (TFB2M). We have silenced the expression of TFB2M by RNA interference in Drosophila melanogaster. RNA interference knockdown of TF2BM causes lethality by arrest of larval development. Molecular analysis demonstrates that TF2BM is essential for mtDNA transcription during Drosophila development and is not redundant with TFB1M. The impairment of mtDNA transcription causes a dramatic decrease in oxidative phosphorylation and mitochondrial ATP synthesis in the long-lived larvae, and a metabolic shift to glycolysis, which partially restores ATP levels and elicits a compensatory response at the nuclear level that increases mitochondrial mass. At the cellular level, the mitochondrial dysfunction induced by TFB2M knockdown causes a severe reduction in cell proliferation without affecting cell growth, and increases the level of apoptosis. In contrast, cell differentiation and morphogenesis are largely unaffected. Our data demonstrate the essential role of TFB2M in mtDNA transcription in a multicellular organism, and reveal the complex cellular, biochemical, and molecular responses induced by impairment of oxidative phosphorylation during Drosophila development.
The impact of infliximab induction therapy on mucosal healing and clinical remission in Polish pediatric patients with moderate-to-severe Crohn’s disease

Objective To assess the clinical efficacy and the impact of infliximab (IFX) induction therapy on mucosal healing in Polish children with Crohn’s disease (CD). Methods A total of 66 children (29 boys and 37 girls) aged 14.06±3.59 years with CD diagnosed at the mean age of 8.4±7.3 years were included in the study. Patients received IFX (5 mg/kg) in three repeated infusions at 0, 2, and 6 weeks. The clinical activity of the disease was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI) and the endoscopic activity was scored using the Simple Endoscopic Score for Crohn’s disease at baseline and at week 10. Results Twenty-two (33%) of the studied patients reached clinical remission (PCDAI⩽10), 26 (39%) showed a clinical response (PCDAI between 15 and 30), and 18 (28%) did not respond to the therapy. When comparing data at baseline and at week 10, significant decreases were observed in the median PCDAI, C-reactive protein, and platelet count. In addition, a significant increase in BMI was noted. A significant decrease in the Simple Endoscopic Score for CD was observed between the initial and the control colonoscopies. Fifteen out of 66 patients (22.7%) had score 0 in the control endoscopy at week 10. No adverse events leading to therapy termination were observed. Conclusion Biological therapy with IFX enables mucosal healing in pediatric patients with CD. Induction therapy with infliximab was found to be clinically effective in 72% of Polish pediatric patients with CD and induced a remission in 33% of them. Induction therapy with infliximab helps to increase BMI.
Visitas de escolares de Educación Primaria a museos de ciencias. Análisis preliminar sobre sus percepciones

Dentro de la educacion no formal en sentido estricto, o de la aprovechada desde la escuela para complementar la formacion impartida en el aula, las visitas a museos de ciencias son cada vez mas consideradas. Este trabajo es continuacion de otro anterior que analizaba las percepciones de los maestros sobre el uso de este recurso. Nos centramos en este caso en la percepcion de los escolares de Educacion Primaria sobre lo que hacen y aprenden en estos espacios. Hemos encontrado que en general estan bastante familiarizados con los museos y que sus visitas suelen estar muy dirigidas por los monitores o guias de los museos. Se detecta tambien una escasa preparacion previa de las visitas,aunque si es mas frecuente realizar actividades posteriores en el aula relacionadas con las mismas.
Predicting cloud droplet number concentration in community atmosphere model (CAM)-Oslo

A continuity equation for cloud droplet number concentration is implemented in an extended version of the National Center for Atmospheric Research (NCAR) Community Atmosphere Model version 2.0. 1 (CAM-2.0.1). The new continuity equation for cloud droplet number concentration consists of a nucleation term and several microphysical sink terms. The nucleation term is calculated based on a parameterization of activation of cloud condensation nuclei. A sub-grid distribution of vertical velocity is used to determine the range of supersaturations found within each model grid box. This supersaturation combined with the hygroscopicity of the aerosols present will determine the number of Cloud Condensation Nuclei (CCN) activated into cloud droplets. The aerosol types considered in this study are sea salt, sulfate, black carbon, organic carbon and mineral dust. The horizontal and vertical distributions of sulfate and carbonaceous aerosols are calculated based on AEROCOM (http://nansen.ipsl.jussieu.fr/AEROCOM) sources. These are combined with the background aerosols, which are a combination of sea salt, mineral dust and sulfate dependent on soil type, wind speed and location (Arctic, Antarctic, maritime, desert or continental). The resulting aerosol size distributions are multimodal, allowing sulfate, black carbon and organic carbon to be both internally and externally mixed with the background aerosols. Microphysical sink termsmore » for cloud droplets are obtained from a prognostic cloud water scheme, assuming a direct proportionality between loss of cloud water and loss of cloud droplets. Based on the framework described above, the cloud droplet number concentration and cloud droplet effective radius can be determined. The resulting cloud radiative forcings (CRF) can hereafter be calculated. By comparing the CRF for two different model runs, one with pre-industrial aerosol sources and the other with sources corresponding to present day, the indirect effect of aerosols can be calculated. A significantly smaller aerosol indirect effect is found in this study compared to most other comparable studies. This is largely due to the introduction of microphysical sinks for cloud droplets and a cloud droplet activation scheme which accounts for the so called competition effect among CCN. « less
Adaptive compounding of synthetic aperture and compounded plane-wave imaging for fast ultrasonography

This paper describes the investigation and implementation of a combined synthetic aperture (SA) and compounded plane wave (CPW) ultrasound imaging technique. Individually, these methods offer unique benefits over the conventional transmit beamforming used in ultrasonography (higher resolution and increased signal-to-noise ratio, respectively), and both have the potential for a higher physical frame rate limit. The technique described combines the individual benefits while maintaining a higher frame rate, by adaptively compounding the resulting images from SA and CPW sequences at half the standard number of transmits. Tests on a phantom with both point scatterers and occlusions showed overall improvements of 14.5% in lateral resolution and 7.5% in axial resolution over CPW, and a 14.5 dB improvement in signal-to-noise ratio (SNR) for occlusions over SA. Both resolution and SNR were an improvement over that for conventional transmit beamforming with two focus depths, and offer double the physical frame rate limit.
Intranasal immunization with heat shock protein 60 induces CD4+CD25+GARP+ and type 1 regulatory T cells and inhibits early atherosclerosis

Atherosclerosis is an autoimmune inflammatory disease involving both innate and adaptive immune mechanisms. Immune tolerance induction may have therapeutic potential for the suppression of atherosclerosis. Current interest is directed towards mucosal tolerance induction, especially nasal tolerance. Previous studies have shown that heat shock protein 60 (HSP60) is recognized as an important autoantigen in atherosclerosis, and nasal or oral HSP60 can induce tolerance and ameliorate atherosclerosis by inducing several subsets of regulatory T cells (Tregs) such as latency‐associated peptide (LAP)+ and forkhead box transcription factor 3 (FoxP3)+ Tregs. However, little is known regarding the detailed mechanisms of nasal tolerance. Here, we again investigated the impact of nasal HSP60 on atherosclerosis and the mechanisms underlying the anti‐atherosclerosis responses. We found that nasal HSP60 caused a significant 33·6% reduction in plaque size at the aortic root in the early stages of atherosclerosis (P < 0·001). Notably, a significant increase in activated CD4+CD25+ glycoprotein A repetitions predominant (GARP)+ Tregs, type 1 Tregs (Tr1 cells), and CD4+CD25+FoxP3+ Tregs, as well as a marked decrease in the numbers of type 1 and 17 T helper cells was detected in the spleens and cervical lymph nodes of HSP60‐treated mice. Moreover, nasal HSP60 increases the production of transforming growth factor (TGF)‐β and interleukin (IL)‐10 and decreases the secretion of IFN‐γ and IL‐17. Interestingly, the atheroprotective role of nasal HSP60 treatment was abrogated partly by the neutralization of IL‐10. Our findings show that nasal administration of HSP60 can attenuate atherosclerotic formation by inducing GARP+ Tregs, Tr1 cells and FoxP3+ Tregs, and that these Tregs maintain immune homeostasis by secreting IL‐10 and TGF‐β.
Integration between point-of-care cardiac markers in an emergency/cardiology department and the central laboratory: methodological and preliminary clinical evaluation

Abstract To achieve rapid assessment of chest pain in emergency/cardiology departments, a short turnaround time for cardiac marker testing is necessary. Nevertheless, Total Quality Management principles must be incorporated into the management of point-of-care testing (POCT); in this setting we implemented the Stratus CS ® assay as POCT for cardiac markers in our emergency/cardiology department. The analytical performance of the troponin I method was evaluated; information connectivity between the Stratus CS ® data management system and the laboratory information system was implemented and practical training of testing personnel was carried out at the POCT site. A total of 41 non-ST-segment elevation patients admitted to the hospital were followed to evaluate the appropriateness of hospital admission, formulated on the basis of the cardiac troponin-I level measured at the POCT site by clinical staff. Our preliminary clinical data suggest that the high sensitivity of the Stratus CS ® troponin method could play an important role in the early identification of patients with acute myocardial infarction in a low to intermediate-risk population for acute coronary syndrome. Our POCT model suggests that the central laboratory could ensure that the POCT program remains in compliance with quality requirements. Nevertheless, our comparison studies suggest that the implementation of POCT requires a high level of integration between cardiologists and pathologists to guarantee appropriate interpretation of the monitoring results for suspected ACS patients.
Filgrastim-mobilized peripheral blood progenitor cells versus bone marrow transplantation for treating leukemia: 3-year results from the EBMT randomized trial.

BACKGROUND AND OBJECTIVES Allogeneic peripheral blood progenitor cells (PBPC) are now widely used as the source of hematopoietic stem cells for transplantation. However, it is still not clear which patients should receive mobilized PBPC or bone marrow cells to reconstitute hematopoiesis after myeloablative conditioning. The aim of this study is to present 3-year-follow-up data on outcome (incidence and severity of chronic graft-versus-host disease (GVHD), overall survival (OS) and leukemia-free survival (LFS) after a PBPC transplant (PBPCT) or a bone marrow transplant (BMT). DESIGN AND METHODS Data on 350 patients with leukemia were collected in a multicenter, randomized study initiated by the EBMT. The patients were randomized to receive filgrastim-mobilized PBSCT or BMT from an HLA-identical donor. RESULTS At a median follow-up of 3 years, significantly more patients transplanted with PBPC than with bone marrow developed chronic GVHD (73% vs 55%, p=0.003) and extensive chronic GvHD (36% vs 19%, p=0.002). The higher incidence and greater severity of chronic GvHD had little impact on the patient's performance status or survival. OS was 58% for PBPCT recipients versus 65% among those undergoing BMT. LFS was 56% for PBPCT recipients versus 60% for BMT recipients. INTERPRETATION AND CONCLUSIONS Patients transplanted with PBPC from an HLA-identical sibling develop more chronic GvHD than those transplanted with bone marrow, but the final impact of this difference is unclear. Longer follow-up is necessary to characterize the impact of chronic GvHD on quality of life, leukemia-free survival and overall survival.
Emergency Department Utilization by Crack-Cocaine Smokers in Dayton, Ohio

The objective of this study was to determine the frequency, principal diagnoses, and correlates of emergency department (ED) visits made by persons with a history of crack-cocaine use (n = 333) over a 3-year period. Data were collected from participant self-reports and hospital records. During the study a total of 643 ED visits were made by 211 people, ranging from 53.5 to 76.7/100 persons/year. Injury and poisoning accounted for the largest single category of ED visits (29.5%). Men had lower odds of visiting the ED (OR = 0.79, 95%CI = 0.62–0.99), as did participants with higher levels of education (OR = 0.83, 95%CI = 0.73–0.94). Number of times in drug abuse treatment (OR = 1.04, 95%CI = 1.01–1.09), having a chronic disease (OR = 1.46, 95%CI = 1.06–1.99), and higher Addiction Severity Index composite medical scores (OR = 1.62, 95%CI = 1.15–2.29) increased the odds of an ED visit. Factors in addition to drug use are likely to affect ED utilization rates among crack-cocaine smokers.
Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY 720

Graft-versus-host disease (GvHD) mediated by donor T cells recognizing host alloantigens is associated with beneficial graft-versus-tumor effects in recipients of allogeneic hematopoietic cell transplants. Since leukemias and lymphomas reside largely within the lymphohematopoietic system, we have proposed that the desired graft-versus-leukemia or graft-versus-lymphoma effect can be separated from the complication of GvHD by confinement of the graft-versus-host alloresponse to the lymphohematopoietic tissues. Since the new sphingosine-1-phosphate receptor agonist immunosuppressive drug FTY720 leads to trapping of T cells in secondary lymphoid tissues, we evaluated the possibility that this drug could diminish GvHD, a disease involving epithelial target tissues, while permitting a beneficial alloresponse to take place within the lymphohematopoietic system, leading to graft-versus-lymphoma effects. We demonstrate here that FTY720 markedly reduces GvHD in a clinically relevant, haploidentical strain combination, while permitting antitumor effects against a T cell lymphoma of unshared host MHC haplotype to proceed unhindered. These results establish a potential new immunotherapeutic approach to separating graft-versus-leukemia effects from GvHD. Article Transplantation
The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa

Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens that infect non‐immunocompromised patients with established lung disease, although they can also cause primary infections. The ability to bind fibronectin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures constructed with human tissue and the contribution of M. avium fibronectin attachment protein (FAP) to the process. MAC adhered to fibrous, but not globular mucus, and to extracellular matrix (ECM) in areas of epithelial damage, but not to intact extruded cells and collagen fibres. Bacteria occasionally adhered to healthy unciliated epithelium and to cells that had degenerated exposing their contents, but never to ciliated cells. The results obtained with different respiratory tissues were similar. Two ATCC strains of MAC gave similar results. There was a significant reduction (P < 0.05) in the number of bacteria adhering to ECM after preincubation of bacteria with fibronectin and after preincubation of the tissue with M. avium FAP in a concentration‐dependant manner. The number of bacteria adhering to fibrous mucus was unchanged. Immunogold labelling demonstrated fibronectin in ECM as well as in other areas of epithelial damage, but only ECM bound FAP. A Mycobacterium smegmatis strain had the same pattern of adherence to the mucosa as MAC. When the FAP gene was deleted, the strain demonstrated reduced adherence to ECM, and adherence was restored when the strain was transfected with an M. avium FAP expression construct. We conclude that MAC adheres to ECM in areas of epithelial damage via FAP and to mucus with a fibrous appearance via another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.
Molecular Basis for Autoregulatory Interaction Between GAE Domain and Hinge Region of GGA1

Golgi‐localizing, γ‐adaptin ear domain homology, ADP ribosylation factor‐binding (GGA) proteins and the adaptor protein (AP) complex, AP‐1, are involved in membrane traffic between the trans Golgi network and the endosomes. The γ‐adaptin ear (GAE) domain of GGAs and the γ1 ear domain of AP‐1 interact with an acidic phenylalanine motif found in accessory proteins. The GAE domain of GGA1 (GGA1‐GAE) interacts with a WNSF‐containing peptide derived from its own hinge region, although the peptide sequence deviates from the standard acidic phenylalanine motif. We report here the structure of GGA1‐GAE in complex with the GGA1 hinge peptide, which revealed that the two aromatic side chains of the WNSF sequence fit into a hydrophobic groove formed by aliphatic portions of the side chains of conserved arginine and lysine residues of GGA1‐GAE, in a similar manner to the interaction between GGA‐GAEs and acidic phenylalanine sequences from the accessory proteins. Fluorescence quenching experiments indicate that the GGA1 hinge region binds to GGA1‐GAE and competes with accessory proteins for binding. Taken together with the previous observation that γ1 ear binds to the GGA1 hinge region, the interaction between the hinge region and the GAE domain underlies the autoregulation of GGA function in clathrin‐mediated trafficking through competing with the accessory proteins and the AP‐1 complex.