Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in the subsets of CD4+ T cells in Trypanosoma musculi infection: delay of immunological cure in young mice and the weak ability of aged mice to control the infection.

After a 3 week course (approximately), during which there is marked lymphoid hyperplasia, Trypanosoma musculi infections in young-adult mice are cured by an immune mechanism involving antibodies of the IgG2a isotype. Both the lymphoid hyperplasia and IgG2a antibody response are T-cell-dependent events and both processes appear to be defective in aged mice. The purpose of the studies reported here was to elucidate the effects of T. musculi infection on subsets of T cells for two reasons: (i) to gain insight into the probable roles of selected cytokines (IL-2, IL-4 and IFN-gamma) in facilitating the production of curative, IgG2a antibodies, and (ii) to examine the hypothesis that aging affects the competence of CD4+ T cells to participate in immunological control of infections. The major conclusions from these studies are that: (i) T. musculi infection of mice induces rapid change in the CD4+ T cell population toward predominance of the activated or memory (CD45RBloCD44hi) phenotype, cells which produce IFN-gamma, II-3, IL-4 and IL-5, accompanied by profound inhibition of IL-2 production, and (ii) in the old mice these changes are superimposed on the natural age-associated changes in the same direction (i.e. toward predominance of CD45RBloCD44hi T cells). Thus, in the old animals, the combined changes of aging and infection, moving in the same direction, are devastating, resulting in the aged animals being unable, or barely able, to control infection.
Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon alpha2a.

BACKGROUND & AIMS Covalent attachment of a 40-kilodalton polyethylene glycol moiety to interferon alpha2a (peginterferon alpha2a) results in sustained delivery and reduced clearance compared with standard interferon alpha2a. The aim of the study was to compare viral kinetics in patients treated with standard or peginterferon alpha2a. METHODS Patients with chronic hepatitis C were randomly assigned to receive either standard interferon alpha2a thrice weekly (n = 16) or 180 microg peginterferon alpha2a once weekly (n = 17) for 48 weeks. HCV RNA was quantitated before and frequently during treatment. RESULTS The extent of the second-phase decline of HCV RNA, representing the degradation rate of infected cells during therapy for responding patients, was 0.02 +/- 0.03 day(-1) (HCV-1), 0.88 +/- 0.64 day(-1) (HCV non-1), 0.06 +/- 0.08 day(-1) (HCV-1), and 0.44 +/- 0.33 day(-1) (HCV non-1) in patients treated with standard or peginterferon alpha2a, respectively. The second-phase decline was low (<0.05 day(-1)) in most patients without a virological end-of-treatment response, and the second-phase decline was high (>0.25 day(-1)) in all patients with sustained virological response. CONCLUSIONS The degradation rate of infected cells is HCV genotype dependent. Treatment with peginterferon alpha2a may reinforce the death rate of infected cells (particularly in HCV-1-infected patients) or stabilize the therapeutic effect on viral production. The second-phase decline of HCV RNA is predictive of virological sustained response.
Increasing delta-9-tetrahydrocannabinol (Δ-9-THC) content in herbal cannabis over time: systematic review and meta-analysis.

AIM The objective of this meta-analysis is to assess the data regarding changes in herbal cannabis potency over time (from 1970 to 2009). METHODS Systematic searches of 17 electronic scientific databases identified studies on this topic, within which 21 case series studies satisfied our inclusion criteria of reporting the mean tetrahydrocannabinol (THC) value per number of samples per year. No language, publication date, publication type or status restrictions were imposed. The study selection and data extraction processes were performed independently but uniformly by two authors, included screening, determination of eligibility and inclusion of the eligible studies in the systematic review, and a meta-analysis of the results on THC content in herbal cannabis samples. We considered papers and not monographic scientific publications, rejecting all studies that were not focused on the subject of this review. RESULTS Meta-analysis by year was performed on 21 studies containing 75 total mean THC observations from 1979 to 2009 using the random effects model. The results revealed much variability between studies. Further, there was a significant correlation between year and mean THC in herbal cannabis. The combined data indicated the correlation between year and mean THC in herbal cannabis, revealing a temporal trend of increasing potency (5% above the mean THC value in the Poisson regression analysis). CONCLUSIONS The results of the analysis suggest that there has been a recent and consistent increase in cannabis potency worldwide.
Prenatal Differentiation of Bovine Oviductal Epithelium: An Electron Microscopic Study

In this study, we investigated the ultrastructural changes during the prenatal differentiation of oviductal epithelium in 16 bovine embryos and fetuses from CRL of 18.0 cm to a CRL of 94.0 cm. Ciliated and secretory cells of bovine uterine tube, a derivative of the Müllerian duct, differentiate to distinct development stages in the prenatal period. The typical cellular pattern, which is generally characteristic for the adult bovine oviduct, is also obtained during fetal life. In the early stages (CRL 18.0/20.4 cm), the bovine oviductal epithelium appears mostly undifferentiated. The epithelial cells show only a few mitochondria, some cisternae of rough endoplasmic reticulum (rER) and a small Golgi‐complex. Most of the cytoplasm is filled with a large amount of glycogen, which decreases during later development. Interspersed between the undifferentiated epithelial cells, a few cells undergoing ciliogenesis can be observed. Ciliogenesis increased significantly during the later prenatal developmental stages. At a CRL of 55.0 cm, ciliated cells appear fully differentiated with mature cells covering their luminal surface. Formation of cilia usually use the acentriolar pathway. Fibrous granules occurred initially in association with the Golgi‐apparatus and r(ER) in the supranuclear cytoplasm. Fibrous granules later fuse with deuterosomes and give rise to procentrioles, which are translocated to the luminal plasma membrane. There they become arranged in a line just beneath the apical cell membrane and further differentiate to basal bodies from which the formation of cilia and striated rootlets take place. Clear signs of differentiation of secretory cells were first seen in our material in fetuses with a CRL of 51.0 cm and 64.0 cm. These cells contain a well developed rER and Golgi‐apparatus with dilated cisterns. In the supranuclear cytoplasm, the number of secretory granules continuously increases during later development and the cells adapt to the morphology of mature secretory cells at the CRL 94.0 cm.
Binding of Xanthine Oxidase to Glycosaminoglycans Limits Inhibition by Oxypurinol*

Although the binding of xanthine oxidase (XO) to glycosaminoglycans (GAGs) results in significant alterations in its catalytic properties, the consequence of XO/GAG immobilization on interactions with clinically relevant inhibitors is unknown. Thus, the inhibition kinetics of oxypurinol for XO was determined using saturating concentrations of xanthine. When XO was bound to a prototypical GAG, heparin-Sepharose 6B (HS6B-XO), the rate of inactivation for uric acid formation from xanthine was less than that for XO in solution (kinact = 0.24 versus 0.39 min–1). Additionally, the overall inhibition constant (Ki) of oxypurinol for HS6B-XO was 2–5-fold greater than for free XO (451 versus 85 nm). Univalent electron flux (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{O}_{2}^{{\bar{{\cdot}}}}\) \end{document} formation) was diminished by the binding of XO to heparin from 28.5% for free XO to 18.7% for GAG-immobilized XO. Similar to the results obtained with HS6B-XO, the binding of XO to bovine aortic endothelial cells rendered the enzyme resistant to inhibition by oxypurinol, achieving ∼50% inhibition. These results reveal that GAG immobilization of XO in both HS6B and cell models substantially limits oxypurinol inhibition of XO, an event that has important relevance for the use of pyrazolo inhibitors of XO in clinical situations where XO and its products may play a pathogenic role.
Inferior infarction following alcohol septal ablation: A consequence of “collateral damage”?

Alcohol septal ablation is fast becoming the most common method to reduce left ventricular outflow tract gradient in patients with symptomatic hypertrophic obstructive cardiomyopathy. Myocardial contrast echocardiography (MCE) is routinely used as an adjunct to avoid the spread of alcohol to non‐target areas of myocardium. We report two cases where despite the careful use of MCE, remote inferior wall myocardial infarctions occurred. The likely mechanism and possible preventive measures are discussed. © 2006 Wiley‐Liss, Inc.
Orthologs of Arabidopsis thaliana stomatal bHLH genes and regulation of stomatal development in grasses

Stomata are adjustable pores in the plant epidermis that regulate gas exchange between the plant and atmosphere; they are present on the aerial portions of most higher plants. Genetic pathways controlling stomatal development and distribution have been described in some detail for one dicot species, Arabidopsis, in which three paralogous bHLH transcription factors, FAMA, MUTE and SPCH, control discrete sequential stages in stomatal development. Orthologs of FAMA, MUTE and SPCH are present in other flowering plants. This observation is of particular interest when considering the grasses, because both the morphology of guard cells and their tissue distributions differ substantially between Arabidopsis and this group. By examining gene expression patterns, insertional mutants and cross-species complementation studies, we find evidence that FAMA function is conserved between monocots and dicots, despite their different stomatal morphologies, whereas the roles of MUTE and two SPCH paralogs are somewhat divergent.
Differential Regulation of Extracellular Tissue Inhibitor of Metalloproteinases-3 Levels by Cell Membrane-bound and Shed Low Density Lipoprotein Receptor-related Protein 1

Background: Tissue inhibitor of metalloproteinases-3 (TIMP-3) is endocytosed, but its regulatory mechanism is not well understood. Results: TIMP-3 endocytosis occurs mainly through low density lipoprotein receptor-related protein-1 (LRP-1), but shed sLRP-1 binds TIMP-3. Conclusion: TIMP-3-sLRP-1 complexes are retained extracellularly with metalloproteinase inhibitory activity. Significance: LRP-1 is the master regulator of extracellular levels of TIMP-3. Tissue inhibitor of metalloproteinases-3 (TIMP-3) plays a key role in regulating extracellular matrix turnover by inhibiting matrix metalloproteinases (MMPs), adamalysins (ADAMs), and adamalysins with thrombospondin motifs (ADAMTSs). We demonstrate that levels of this physiologically important inhibitor can be regulated post-translationally by endocytosis. TIMP-3 was endocytosed and degraded by a number of cell types including chondrocytes, fibroblasts, and monocytes, and we found that the endocytic receptor low density lipoprotein receptor-related protein-1 (LRP-1) plays a major role in TIMP-3 internalization. However, the cellular uptake of TIMP-3 significantly slowed down after 10 h due to shedding of LRP-1 from the cell surface and formation of soluble LRP-1 (sLRP-1)-TIMP-3 complexes. Addition of TIMP-3 to HTB94 human chondrosarcoma cells increased the release of sLRP-1 fragments of 500, 215, 160, and 110 kDa into the medium in a concentration-dependent manner, and all of these fragments were able to bind to TIMP-3. TIMP-3 bound to sLRP-1, which was resistant to endocytosis, retained its inhibitory activity against metalloproteinases. Extracellular levels of sLRP-1 can thus increase the half-life of TIMP-3 in the extracellular space, controlling the bioavailability of TIMP-3 to inhibit metalloproteinases.
Southern Romance: Relationship Quality, Consensus, and Context among Cohabiting Couples in the Gulf States

Abstract Relationships are significantly stressed in the Southeastern United States. Of the six states in the Gulf region (Florida, Georgia, Alabama, Mississippi, Louisiana, and Texas), four are in the top-third of the nation's highest divorce rates. Threats to relationship household stability cause a myriad of social problems and public expenses of approximately $24 billion in increased spending in benefit programs to offset family hardship following divorce and relationship dissolution. This study analyzed associations between relationship quality and satisfaction, consensus, and a series of contextual variables among three types of cohabiting homeowners across the Gulf States (unmarried, married, and married with additional family members), surveying variables of interest. Findings indicated that dyadic couple relationships in this sample are generally distressed relative to other states and that significant negativity is present, but that a large portion of the variance in relationship quality is consistently predicted by certain factors. Using an instrument of increased sensitivity, these factors (consensus, negative interaction, household composition, etc.) have been parsed into specific components (types of consensus, types of interaction, etc.) for improved individual analysis. Specific relationship problem areas are outlined, clarified, and discussed.
GAT2/BGT-1 as a System Responsible for the Transport of γ-Aminobutyric Acid at the Mouse Blood–Brain Barrier

In this study, the γ-aminobutyric acid (GABA) transporter at the blood–brain barrier (BBB) was identified by reverse transcription–polymerase chain reaction (RT-PCR), Western blot, and immunostaining analysis, and the transport mechanism was characterized using a conditionally immortalized mouse brain capillary endothelial cell line (TM-BBB) as an in vitro model of the BBB. γ-Aminobutyric acid transport was studied by the cellular uptake of [3H]GABA. [3H]GABA uptake by TM-BBB cells was Na+−, Cl−-, and concentration-dependent. The corresponding Michaelis–Menten constant was 679 ± 80 μmol/L and the maximal uptake rate was 4,790 ± 494 pmol/(mg protein · 5 minutes). [3 H]GABA uptake by TM-BBB cells was significantly inhibited by betaine, β-alanine, nipecotic acid, taurine, and quinidine, whereas probenecid, L-proline, creatine, and glycine had no effect. This type of inhibition is consistent with the predominant involvement of the GAT2/BGT-1 transporter in TM-BBB cells. RT-PCR analysis showed that GAT2/BGT-1 mRNA was expressed in TM-BBB cells, whereas Western blot analysis showed that TM-BBB cells and mouse brain capillaries express GAT2/BGT-1 protein. Moreover, confocal immunofluorescent microscopy of dual-labeled mouse brain sections demonstrated the colocalization of GAT2/BGT-1 and P-glycoprotein, a BBB-specific marker, on brain capillaries labeled with anti–GAT2/BGT-1 antibody and anti–P-glycoprotein antibody, respectively. These results are evidence that GAT2/BGT-1 is expressed at the BBB and is involved in GABA transport across the BBB.
Acute and chronic hypoxia as well as 7‐day recovery from chronic hypoxia affects the distribution of pulmonary mast cells and their MMP‐13 expression in rats

Chronic hypoxia results in pulmonary hypertension due to vasoconstriction and structural remodelling of peripheral lung blood vessels. We hypothesize that vascular remodelling is initiated in the walls of prealveolar pulmonary arteries by collagenolytic metalloproteinases (MMP) released from activated mast cells. Distribution of mast cells and their expression of interstitial collagenase, MMP‐13, in lung conduit, small muscular, and prealveolar arteries was determined quantitatively in rats exposed for 4 and 20 days to hypoxia as well as after 7‐day recovery from 20‐day hypoxia (10% O2). Mast cells were identified using Toluidine Blue staining, and MMP‐13 expression was detected using monoclonal antibody. After 4, but not after 20 days of hypoxia, a significant increase in the number of mast cells and their MMP‐13 expression was found within walls of prealveolar arteries. In rats exposed for 20 days, MMP‐13 positive mast cells accumulated within the walls of conduit arteries and subpleurally. In recovered rats, MMP‐13 positive mast cells gathered at the prealveolar arterial level as well as in the walls of small muscular arteries; these mast cells stayed also in the conduit part of the pulmonary vasculature. These data support the hypothesis that perivascular pulmonary mast cells contribute to the vascular remodelling in hypoxic pulmonary hypertension in rats by releasing interstitial collagenase.
Behavioral Effects of Withholding Taxes on Labor Supply

Income tax collection in most advanced economies uses third-party reporting and withholding at the employer level before the employee receives her wage income. Since withholding taxes do not necessarily reflect the true effective tax burden, they may give false signals on the net-of-tax pay. We report results of laboratory experiments in which labor supply effects of such misperceptions are tested. Withholding taxes (and resulting tax refunds) should be behaviorally neutral in the experiment, but our results suggest that withholding taxes reduce effort and tax adjustments lead to adjustments of effort for our most relevant group of participants, those motivated by monetary incentives. This indicates that withholding taxes may be behaviorally relevant and deserve attention of policy-makers
The role of ecologic diversification in sibling speciation of Empidonax flycatchers (Tyrannidae): multigene evidence from mtDNA

Avian genera characterized by sibling species with distinctive habitat preferences present an evolutionary enigma in view of the more commonplace occurrence of syntopic congeners that differ strikingly in colour and pattern. No existing theory has explained the evolutionary background that led to these differences. Here we propose that great phenotypic similarity among some groups of sibling species limits their coexistence and that clues to their radiation can be seen in patterns of geographical occurrence. To illustrate our thesis we focused on the New World flycatcher genus Empidonax, a group of 15 species notorious for their great phenotypic similarity. Using 3069 base pairs of mitochondrial DNA from four genes, we produced a complete molecular phylogeny that identified four clades, three of which represent close relatives. The fourth clade includes only E. virescens, which apparently has no close living relatives. The majority of species, including many distant relatives, are completely (58.1%) or essentially (6.7%) allopatric in breeding distribution and exhibit striking ecological segregation into distinctive climate–vegetation zones. Even where ranges overlap, occupancy of the same habitat by different species is rare. Phylogenetic and distributional patterns in Empidonax suggest a peripatric model of stepwise colonization and then range expansion of small groups of pioneers during glacial periods into initially enlarging, distinctive habitats destined to be widespread during interglacials. Vicariance is not indicated in the absence of barriers of appropriate age and geographical position. Rapoport's rule that northern species have larger ranges than southern species is strongly supported.
Singing voice and pregnancy - preliminary results from a case study

During pregnancy significant changes in bodily tissues occur. For example, the cervix undergoes deep structural/biomechanical alterations due to an increase in concentration of progesterone. Previous studies have found a significant correlation between the changes that both cervical and vocal fold smears undergo during the menstrual cycle, demonstrating a relevant hormonal influence on laryngeal tissues. It can be hypothesised that such tissue changes that may occur during pregnancy affect conditions for phonation with respect to e.g. Vocal fold motility. To test this hypothesis recordings of audio, electrolaryngograph, oral pressure and air flow signals were made during pregnancy, at birth and after pregnancy of a semi-professional classically trained soprano. The tasks involved repetitions of the syllable [pae] while performing a diminuendo at various pitches, thus allowing determination of the lowest pressures producing vocal fold vibration and vocal fold contact, i.e. The phonation and contact threshold pressures. Oral pressure during the occlusion for the consonant [p] was accepted as a measure of subglottal pressure. Concentrations of sex female steroid hormones were measured during pregnancy, at birth and post-partum. Results showed a steep decrease of concentrations of progesterone and oestrogens from pregnancy to post-partum conditions. Likewise, phonation and collision thresholds decreased markedly at birth and post-partum, shifts that are in accordance with expectations based on the effects of sex steroid hormones on tissue viscosity and water retention. The results thus demonstrate an effect of pregnancy on the voice.
Selective Estrogen Receptor Modulators (SERMs) in Clinical Practice

The objective of this literature review is to familiarize the reader with the clinical data on selective estrogen receptor modulators (SERMs) and antiestrogens currently in use in the US, excluding data on breast effects. Four compounds in the SERM and antiestrogen families are presently in clinical use in the US: clomiphene (CC), tamoxifen (TAM), toremifene (TOR), and raloxifene (RLX). The clinical databse on these compounds is among the largest available. Each compound demonstrates a specific profile for its target tissue effects, and this may differ between premenopausal and postmenopausal women. CC is the most widely used agent for ovulation induction. TAM is indicated in the management of breast cancer and for prevention in women at high risk. TAM may have additional effects on the cardiovascular and skeleal systems. TOR also is used for its effects on breast tissue and may have positive cardiovascular effects. RLX is approved in the management of osteoporosis with data supporting favorable effects on the cardiovascular system and breast tissue. TAM and TOR appear to have stimulatory effects on the uterus and endometrium, whereas RLX is neutral. Few adverse events have been attributed to these agents, with hot flashes being the most common one. There appears to be an increased risk of thromboembolic events with continuous use of TAM, TOR, and RLX. SERMs and antiestrogens continue to be studied extensively. Their evolving profiles support key roles for these agents in modern day medicine, particularly in the management of postmenopausal women's health.