Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiation of human dendritic cells from monocytes in vitro

Since either macrophages (Mϕ) or dendritic cells (DC) differentiate from monocytes (MO) depending on culture conditions, we investigated the relationship of the DC and Mϕ differentiation pathways. Culturing MO‐enriched blood mononuclear cells with Mϕ colony‐stimulating factor (M‐CSF) or with granulocyte/Mϕ (GM)‐CSF induced Mϕ with a different morphology and CD14/CD1a expression. In contrast, in cultures with GM‐CSF and interleukin (IL)‐4, cells rapidly became nonadherent and acquired DC morphology, ultrastructure, CD1a expression, and most DC markers; they lost membrane CD14 and CD64 and capacity of phagocytosis, displayed less CD68 than Mϕ, but retained nonspecific esterase activity. These DC directly developed from MO without proliferation inasmuch as only day 0 FACS‐sorted MO, but not small CD14− cells, differentiated into DC when cultured with GM‐CSF and IL‐4, or to Mϕ with M‐CSF. While overall cell numbers declined, DC numbers plateaued from culture day 2 onwards, indicating that most had differentiasted by then. This differentiation was radioresistant and occurred without [3H]thymidine incorporation. Commitment to differentiate into DC with GM‐CSF and IL‐4 was irreversible by day 2, since discontinuing IL‐4 at this point did not revert cells to Mϕ. Alternatively, cells rapidly converted to DC when IL‐4 was added from day 2 to cultures initiated with GM‐CSF only. If cultures were initiated with M‐CSF and switched to GM‐CSF and IL‐4 after 2 or 5 days, about half of the cells still converted to DC. Thus, the capacity of MO and even of Mϕ to differentiate into DC was conserved for at least this period. The increased capacity to stimulate the mixed leukocyte reaction correlated with the relative number of CD1a− cells at any time and under each condition tested, a confirmation that these cells functionally qualify as DC. Thus, MO and even Mϕ can be directed to differentiate into DC depending on the cytokine microenvironment.
Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor

In late pregnancy rapidly increasing fetal growth dramatically increases uterine wall tension. This process has been implicated in the activation of the myometrium for labor, but the mechanisms involved are unclear. Here, we tested, using a rat model, the hypothesis that gestation‐dependent stretch, via activation of focal adhesion signaling, contributes to the published activation of myometrial ERK at the end of pregnancy. Consistent with this hypothesis, we show here that ERK is targeted to adhesion plaques during late pregnancy. Furthermore, myometrial stretch triggers a dramatic increase in myometrial contractility and ERK and caldesmon phosphorylation, confirming the presence of stretch sensitive myometrial signaling element. Screening by anti‐phosphotyrosine immunoblotting for focal adhesion signaling in response to stretch reveals a significant increase in the tyrosine phosphorylated bands identified as focal adhesion kinase (FAK), A‐Raf, paxillin, and Src. Pretreatment with PP2, a Src inhibitor, significantly suppresses the stretch‐induced increases in FAK, paxillin, Src, ERK and caldesmon phosphorylation and myometrial contractility. Thus, focal adhesion‐Src signaling contributes to ERK activation and promotes contraction in late pregnancy. These results point to focal adhesion signaling molecules as potential targets in the modulation of the myometrial contractility and the onset of labor. J. Cell. Biochem. 100: 129–140, 2007. © 2006 Wiley‐Liss, Inc.
A bi-parameter distance criterion for flange climb derailment

Transportation Technology Center, Inc. (TTCI), a wholly owned subsidiary of the Association of American Railroads (AAR), has developed a bi-parameter flange climb distance criterion for vehicles with an AAR-IB wheel/AREMA 136-pound rail profile combination. This criterion is based on tests and simulation results using TTCFs track loading vehicle (TLV) and a NUCARS/spl trade/ simulation model. The bi-linear characteristics between the transformed climb distance and the two parameters, angle of attack (AOA) and lateral-to-vertical (L/V) force ratio, was obtained through a nonlinear transformation. The accuracy of the fitting formula is further improved by using the gradual linearization methodology. The bi-parameter distance criterion, based on the simulation results, has been validated by TLV test data. This paper also presents the application to two AAR Chapter XI performance acceptance tests and limitations of the bi-parameter criterion.
Issues that impact on Aboriginal health workers' and registered nurses' provision of diabetes health care in rural and remote health settings.

UNLABELLED Type 2 diabetes mellitus is an established health problem for Indigenous Australians. One strategy to address this issue is to educate health professionals in diabetes management and education. OBJECTIVE The objective of this paper is to identify important issues that compromise the clinical practice of rural and remote Aboriginal health workers (AHWs) and registered nurses (RNs) who undertook an accredited Australian Diabetes Educators Association diabetes course and to suggest strategies to improve practice. DESIGN The design used a qualitative approach and discussion schedule to elicit responses. SETTING The setting involved two Aboriginal community controlled and seven mainstream health services in the Far Western region of New South Wales. PARTICIPANTS The participants were experienced diabetes educators (RNs and AHWs), managers and students currently enrolled in the course (n = 17). RESULTS The results indicated issues that compromise diabetes practice and identified strategies to improve practice. Issues were: the confusing funding practices by health providers, the duplication of health services, the lack of recognition of diabetes qualifications and the transient nature of Indigenous people. Strategies included the need for: continuous dedicated diabetes health funding, a role clarification for diabetes educators, strategic diabetes planning and the importance of diabetes educators working in partnership. CONCLUSION The conclusion from this study indicates that if the delivery of diabetes health services to Indigenous Australians is to improve it is necessary to address these identified issues.
Characterization of Plasmin-mediated Activation of Plasma Procarboxypeptidase B

Plasma carboxypeptidase B (PCB) is an exopeptidase that exerts an antifibrinolytic effect by releasing C-terminal Lys and Arg residues from partially degraded fibrin. PCB is produced in plasma via limited proteolysis of the zymogen, pro-PCB. In this report, we show that the K m (55 nm) for plasmin-catalyzed activation of pro-PCB is similar to the plasma concentration of pro-PCB (50–70 nm), whereas the K m for the thrombin- or thrombin:thrombomodulin-catalyzed reaction is 10–40-fold higher than the pro-PCB level in plasma. Additionally, tissue-type plasminogen activator triggers activation of pro-PCB in blood plasma in a reaction that is stimulated by a neutralizing antibody versusα2-antiplasmin. Together, these results show that plasmin-mediated activation of pro-PCB can occur in blood plasma. Heparin (UH) and other anionic glycosaminoglycans stimulate pro-PCB activation by plasmin but not by thrombin or thrombin:thrombomodulin. Pro-PCB is a more favorable substrate for plasmin in the presence of UH (16-fold increase ink cat/K m ). UH also stabilizes PCB against spontaneous inactivation. The presence of UH in clots prepared with prothrombin-deficient plasma delays tissue-type plasminogen activator-triggered lysis; this effect of UH on clot lysis is blocked by a PCB inhibitor from potato tubers. These results show that UH accelerates plasmin-catalyzed activation of pro-PCB in plasma and PCB, in turn, stabilizes fibrin against fibrinolysis. We propose that glycosaminoglycans in the subendothelial extracellular matrix serve to augment the levels of PCB activity thereby stabilizing blood clots at sites where there is a breach in the integrity of the vasculature.
Immunolocalization of NA+,K+-ATPase in the Branchial Cavity During the Early Development of the European Lobster Homarus Gammarus (Crustacea, Decapoda)

We examined the ontogeny of the osmoregulatory sites of the branchial cavity in embryonic and early postembryonic stages of the European lobster Homarus gammarus through transmission electron microscopy, immunofluorescence microscopy, and immunogold electron microscopy using a monoclonal antibody IgGα5 raised against the avian α-subunit of the Na+,K+-ATPase. In mid-late embryos, Na+,K+-ATPase was located along the pleurites and within the epipodite buds. In late embryos just before hatching, the enzyme was confined to the epipodite epithelia. After hatching, slight differentiations of ionocytes occured in the epipodites of larval stages. Na+,K+-ATPase was also located in the ionocytes of the epipodites of larvae exposed to seawater (35.0‰) and to dilute seawater (22.1 ‰). After metamorphosis, the inner-side branchiostegite epithelium appeared as an additional site of enzyme location in postlarvae held in dilute seawater. Within the ionocytes, Na+,K+-ATP-ase was mostly located along the basolateral infoldings. These observations are discussed in relation to the physiological shift from osmoconforming larvae to slightly hyper-regulating (in dilute seawater) postmetamorphic stages. The acquisition of the ability to hyper-osmo-regulate probably originates from the differentiation, on the epipodites and mainly along the branchiostegites, of ionocytes that are the site of ion pumping as evidenced by the location of Na+,K+-ATPase. (J Histochem Cytochem 49:1013–1023, 2001)
Sexual dimorphism of hepatic 11 beta-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the reversible metabolism of corticosterone to inert 11-dehydrocorticosterone. At least two isoforms exist. 11 beta-HSD-1, the first to be characterised and the only isoform for which a cDNA has been isolated, is highly expressed in liver, kidney and hippocampus. The activity of 11 beta-HSD in rat liver is higher in males, due to oestrogen repression of 11 beta-HSD-1 gene transcription in females. Sexual dimorphism in rodent liver proteins is frequently mediated indirectly via sex-specific patterns of GH release (continuous in females, pulsatile in males). We have now investigated whether this applies to 11 beta-HSD, using dwarf rats (congenitally deficient in GH) and hypophysectomised animals. 11 beta-HSD activity and 11 beta-HSD-1 mRNA expression in liver was significantly lower in control female than male rats (50% and 72% of male levels respectively). These sex differences in the liver were attenuated in dwarf rats, with both males and females showing similar levels of 11 beta-HSD activity to control males. Administration of continuous (female pattern) GH to dwarf male rats decreased hepatic 11 beta-HSD activity (30% fall) and mRNA expression (77% fall), whereas the same total daily dose of GH given in the male (pulsatile) pattern had no effect on hepatic 11 beta-HSD in female dwarf rats. Continuous GH also attenuated hepatic 11 beta-HSD activity (25% fall) and 11 beta-HSD-1 mRNA expression (82% fall) in hypophysectomised animals. (ABSTRACT TRUNCATED AT 250 WORDS)
Anti‐inflammatory treatment for recurrent wheezing in the first five years of life

Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long‐term safety when administered in preschool‐age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school‐age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low‐dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long‐term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241–252. © 2003 Wiley‐Liss, Inc.
Regional differences in the effects of septic shock on vascular reactivity in the rabbit.

Experiments were performed to investigate the vascular reactivity in both large and resistance artery preparations from an animal model of septic shock. New Zealand White rabbits were injected with a priming dose of Escherichia coli lipopolysaccharide (LPS), 15 micrograms/kg i.v. , 18 hr before an i.v. dose of 200 to 2000 micrograms/kg under pentobarbital anesthesia. The second LPS challenge dropped mean blood pressure from 79 +/- 4 to 27 +/- 5 mm Hg in approximately 1 hr. At this time animals were sacrificed with the central ear arteries and kidneys being isolated for alignment in a Krebs-bicarbonate buffer perfusion apparatus to monitor perfusion pressure under constant flow conditions. Individual dose-response curves (DRCs) for norepinephrine (NE) and histamine were performed to assess contractile function. For examining vascular relaxant function, DRCs for methacholine (MC) and nitroprusside (NP) were conducted during a submaximal infusion of NE. The DRCs to NE and histamine were shifted to the right by 2- and 2.7-fold, respectively, in isolated ear artery preparations from LPS-treated vs. vehicle-treated animals. There was no difference in contractile function (using NE) in the two groups of perfused kidneys. The relaxation DRCs to MC were similar in the ear artery preparations from the two treatment groups whereas, in isolated kidneys, the relaxation to MC was significantly attenuated, by an average of 26 +/- 2% at each of six doses, in preparations from LPS-treated animals. The relaxation to NP was similar between the LPS- and vehicle-treated animals in the ear artery and kidney preparations. (ABSTRACT TRUNCATED AT 250 WORDS)
Methotrexate treatment of unilateral twin ectopic pregnancy: case report and pharmacokinetic considerations

We describe a case of spontaneous twin ectopic pregnancy, managed with the combination of local injection under ultrasound control and intramuscular administration of methotrexate. We describe a difference between the area under the curve of declining plasma concentration of methotrexate after intramuscular and local injection. Copyright © 1993 International Society of Ultrasound in Obstetrics and Gynecology
Anterior commissure of the wallaby (Macropus eugenii): Adult morphology and development

In metatheria, all neo‐ and paleo‐cortical commissural connections are made by the anterior commissure. We have examined the adult morphology of this commissure and its development in a diprotodontid metatherian, the wallaby (Macropus eugenii), at both the light and electron microscope level. The total number of axons in the adult anterior commissure was 21.7 million, of which 55–62% were myelinated. The dorsal two thirds of the commissure, containing neocortical commissural axons, showed a higher percentage of larger, myelinated axons than the ventral one third, which contains paleocortical commissural axons. The commissure also showed a topographical gradient, with cells in the dorsal cortex projecting through the dorsal region of the commissure, the fasciculus aberrans. In the rostrocaudal axis, axons from the frontal cortex tended to pass more anteriorly through the commissure and those from the occipital more posteriorly, but there was extensive overlap of projections from different areas.
Management of the returning traveler with diarrhea

Traveler’s diarrhea (TD) strikes 20 60% of travelers visiting developing countries. It occurs shortly after the return and can be distinguished into two categories: acute and persistent TD. Acute TD, mostly caused by bacterial and viral pathogens, is usually mild and self-limited, and deserves empirical symptomatic and/or antibiotic therapy in selected cases. Fluoroquinolones are progressively superseded in this indication by azithromycin, a well tolerated macrolide active against most bacteria responsible for TD, including the quinolone-resistant species of Campylobacter jejuni that are now pervasive, especially in Southeast Asia and India. Persistent TD in the returning traveler is much rarer than its acute counterpart and may be associated with three types of causes. Persistent infections, among which Giardia and possibly Entamoeba predominate, account for a significant proportion of cases. Postinfectious processes represent a second cause and comprise temporary lactose malabsorption and postinfectious irritable bowel syndrome, now considered a major cause of persistent TD. Finally, apparently unrelated chronic diseases causing diarrhea are occasionally unmasked by TD and represent a third type of persistent TD, among which the well established case of incident inflammatory bowel disease poses intriguing pathogenesis questions. This review discusses recent advances in the field and provides practical recommendations for the management of TD in adult, immunocompetent returning travelers.
Effects of fatigue and reduced intracellular pH on segment dynamics in ‘isometric’ relaxation of frog muscle fibres.

1. Longitudinal movements of marked segments of single fibres from the anterior tibialis muscle were recorded during tetanus and relaxation under isometric (fixed‐end) conditions. 2. During relaxation, shortening and lengthening of different segments occurred simultaneously, starting at about the same time as the end of the linear fall of force (shoulder on the force record). 3. Variations in intracellular pH, measured with pH‐sensitive microelectrodes, along the length of fibres were not statistically significant, and are unlikely to be responsible for the non‐uniform behaviour of different segments. 4. As expected from earlier studies, both fatigue (produced by increasing tetanus duration or decreasing the time between tetani) and intracellular acidification (produced by raised extracellular CO2), reduced the tetanus force and prolonged the linear phase of force decline in relaxation. Each treatment delayed the start and markedly reduced the amount of segment movement in relaxation. 5. Fatigue and intracellular acidification have a smaller effect on force during stretching than on force produced under isometric conditions. This may contribute to making the segments behave in a more uniform way during relaxation under these conditions. 6. Changes in the Ca2+ uptake mechanisms are also discussed as possible causes for the changes in segment behaviour in relaxation.
Hepatocyte nuclear factor 4 (cid:1) orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver

Epithelial formation is a central facet of organogenesis that relies on intercellular junction assembly to create functionally distinct apical and basal cell surfaces. How this process is regulated during embryonic development remains obscure. Previous studies using conditional knockout mice have shown that loss of hepatocyte nuclear factor 4 (cid:1) (HNF4 (cid:1) ) blocks the epithelial transformation of the fetal liver, suggesting that HNF4 (cid:1) is a central regulator of epithelial morphogenesis. Although HNF4 (cid:1) -null hepatocytes do not express E-cadherin (also called CDH1), we show here that E-cadherin is dispensable for liver development, implying that HNF4 (cid:1) regulates additional aspects of epithelial formation. Mi-croarray and molecular analyses reveal that HNF4 (cid:1) regulates the developmental expression of a myriad of proteins required for cell junction assembly and adhesion. Our ﬁndings deﬁne a fundamen-tal mechanism through which generation of tissue epithelia during development is coordinated with the onset of organ function.
Factors that regulate insulin producing cells and their output in Drosophila

Insulin-like peptides (ILPs) and growth factors (IGFs) not only regulate development, growth, reproduction, metabolism, stress resistance, and lifespan, but also certain behaviors and cognitive functions. ILPs, IGFs, their tyrosine kinase receptors and downstream signaling components have been largely conserved over animal evolution. Eight ILPs have been identified in Drosophila (DILP1-8) and they display cell and stage-specific expression patterns. Only one insulin receptor, dInR, is known in Drosophila and most other invertebrates. Nevertheless, the different DILPs are independently regulated transcriptionally and appear to have distinct functions, although some functional redundancy has been revealed. This review summarizes what is known about regulation of production and release of DILPs in Drosophila with focus on insulin signaling in the daily life of the fly. Under what conditions are DILP-producing cells (IPCs) activated and which factors have been identified in control of IPC activity in larvae and adult flies? The brain IPCs that produce DILP2, 3 and 5 are indirectly targeted by DILP6 and a leptin-like factor from the fat body, as well as directly by a few neurotransmitters and neuropeptides. Serotonin, octopamine, GABA, short neuropeptide F (sNPF), corazonin and tachykinin-related peptide have been identified in Drosophila as regulators of IPCs. The GABAergic cells that inhibit IPCs and DILP release are in turn targeted by a leptin-like peptide (unpaired 2) from the fat body, and the IPC-stimulating corazonin/sNPF neurons may be targeted by gut-derived peptides. We also discuss physiological conditions under which IPC activity may be regulated, including nutritional states, stress and diapause induction.
Highly efficient biallelic genome editing of human ES/iPS cells using a CRISPR/Cas9 or TALEN system

Abstract Genome editing research of human ES/iPS cells has been accelerated by clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) and transcription activator-like effector nucleases (TALEN) technologies. However, the efficiency of biallelic genetic engineering in transcriptionally inactive genes is still low, unlike that in transcriptionally active genes. To enhance the biallelic homologous recombination efficiency in human ES/iPS cells, we performed screenings of accessorial genes and compounds. We found that RAD51 overexpression and valproic acid treatment enhanced biallelic-targeting efficiency in human ES/iPS cells regardless of the transcriptional activity of the targeted locus. Importantly, RAD51 overexpression and valproic acid treatment synergistically increased the biallelic homologous recombination efficiency. Our findings would facilitate genome editing study using human ES/iPS cells.