Miracle-dz/UniFAR-FTUs huggingface dataset:
Differentiation of major genotypes of Giardia intestinalis by polymerase chain reaction analysis of a gene encoding a trophozoite surface antigen

SUMMARY The polymerase chain reaction (PCR) has been used to amplify in vitro a semi-conserved region of a gene encoding an Mr 68–72000 surface antigen of Giardia intestinalis trophozoites. Using primers specific for conserved nucleotide sequences identified within the promoter-distal portion of two homologous genes (tsp11 and tsa417) cloned previously from the G. intestinalis isolates Ad-1 (from Australia) and WB (from Afghanistan), a single PCR-amplified DNA fragment of the expected size (0·52 kilobases) was obtained in high yield from either purified DNA or whole trophozoites of the Ad-1 isolate and from every 1 of 9 other axenic G. intestinalis isolates belonging to genetic groups I and II (defined previously on the basis of allozyme electrophoresis data—Andrews et al. 1989). Discernible product was recovered from as few as 2–4 trophozoites. In contrast, 6 G. intestinalis isolates that were assigned by allozymic analysis to genetic groups III/IV yielded small amounts of a 0·37-kilobase (kb) amplification product (with evidence in some samples of an additional 0·4 or 0·18 kb fragment) but no 0·52 kb product. Two animal-derived isolates of G. duodenalis (one from an Australian native rodent, Notomys alexis, the other from a domestic cat) also yielded a single 0·37 kb PCR-amplified fragment, whereas an isolate from another cat produced a 0·34 kb fragment. No product was recovered from G. muris, a morphologically distinct species of Giardia. The results demonstrate that different genotypes of G. duodenalis can be distinguished using this assay and that it is diagnostic for isolates belonging to two major clusters (groups I/II and III/IV) of G. intestinalis. The amplified DNA segment appears to be relatively conserved among group I and group II isolates of G. intestinalis. A related but clearly distinct sequence seems to be conserved among group III/IV isolates of G. intestinalis and some isolates of G. duodenalis.
The labour market impact of immigration

In the first part of this paper, we present a stylized model of the labour market impact of immigration. We then discuss mechanisms through which an economy can adjust to immigration: changes in factor prices, output mix, and production technology. In the second part, we explain the problems of empirically estimating how immigration affects labour market outcomes of the resident population and review some strategies to address these. We then summarize some recent empirical studies for the UK and other countries. We conclude with an outlook on what we believe are important avenues for future research.
Using Aspects and the Spring Framework to Implement Variabilities in a Software Product Line

Software Product Line (SPL) is one of the most adopted techniques to enable software reuse. Aspect-orientation (AOSD) has been investigated to implement variabilities in component-based SPL. This paper presents an experience on the implementation of SPL variabilities using AOSD. The Spring framework is used to configure the components of an existing SPL architecture. This paper compares the AOSD version of an SPL with an existing component-based one. Lessons learned are discussed regarding the use of AOSD in component-based SPL configured with the Spring framework.
Clinical Application of a Complex of Blood Pressure Profile, Arterial Stiffness and Albuminuria for Cardiorenal Risk Assessment in Diabetic Patients

Background: In modern epidemiology, risk assessment is a crucial step in diabetes care. Clinic blood pressure reading though is not a good measurement for this purpose since both uncontrolled hypertension and white coat hypertension (WCH) are frequent among patients with diabetes mellitus (DM). Given the problems with clinical application of ambulatory blood pressure monitoring (ABPM), in this study we evaluated clinical utility of home self measurement (HSM) with a wrist-cuff device in DM patients with hypertension to make a BP profile. Also, the clinical application of a complex of arterial study, albuminuria and blood pressure profile, in DM risk assessment was investigated. Methods and Materials: Seventy-eight adult DM patients with labile or uncontrolled hypertension were randomly assigned to 24 hour ABPM or HSM for 4 consecutive days and their BP profiles were evaluated in conjunction with an assessment of arterial stiffness and renal function as well as lipid profile. Results: The two groups were of comparable age, gender, BP, DM duration and control, smoking, lipids, renal function, arterial compliance and antihypertensive medication use. ABPM detected 33% WCH and 17.6% evening/night-time dipping, compared to 32% and 16% respectively for HSM, with overlapping 95% confidence intervals for day versus night BP regression coefficients. WCH patients had more compliant arteries as well as less albuminuria compared to the sustained hypertensive group. Conclusion: A complex of BP profile (by either ABPM or HSM), arterial compliance and albuminuria is a reliable and economical alternative to current methods for risk assessment in hypertensive diabetic patients.
Effect of a Metacognitive Scaffolding on Information Web Search.

The objective of the research was to determine the effect that a metacognitive scaffolding for Web information searches exercises on the development of school students, through a general chemistry course in a blended learning modality. One hundred and four students from a school of the city of Bogota D.C.‑Colombia participated in the study. The research followed a quasi‑experimental design with a pretest and posttest. Three tenth‑grade groups, previously established, worked with a b‑learning environment with three versions: the first group worked with a fixed scaffolding, the second with an optional scaffolding, and the third group interacted with a b‑learning environment without any type of scaffolding whatsoever. The Metacognitive Awareness Inventory (MAI) test was used to measure metacognitive abilities before and after data treatment. To analyze the data, a Multivariate Analysis of Covariance (MANCOVA) was conducted, which showed that the fixed scaffolding favors the development of metacognitive abilities, especially those related to procedural knowledge, planning, organization, monitoring, and evaluation. This tool, possibly based on the analysis and reflection of their own performance in task development, allowed students to consolidate structured strategies in Web information searches. In contrast, the use of the optional scaffolding did not exhibit the expected results since it was not used by a high percentage of students. These findings, among others, are discussed in the study.
Leishmania donovani development in Phlebotomus argentipes: comparison of promastigote- and amastigote-initiated infections

SUMMARY Leishmania parasites alternate in their life cycle between promastigote stages that develop in the gut of phlebotomine sand flies and amastigotes residing inside phagocytic cells of vertebrate hosts. For experimental infections of sand flies, promastigotes are frequently used as this way of infection is technically easier although ingestion of promastigotes by sand flies is unnatural. Here we aimed to answer a critical question, to what extent do promastigote-initiated experimental infections differ from those initiated with intracellular amastigotes. We performed side-by-side comparison of Leishmania development in Phlebotomus argentipes females infected alternatively with promastigotes from log-phase cultures or amastigotes grown ex vivo in macrophages. Early stage infections showed substantial differences in parasite load and representation of morphological forms. The differences disappeared along the maturation of infections; both groups developed heavy late-stage infections with colonization of the stomodeal valve, uniform representation of infective metacyclics and equal efficiency of transmission. The results showed that studies focusing on early phase of Leishmania development in sand flies should be initiated with intracellular amastigotes. However, the use of promastigote stages for sand fly infections does not alter significantly the final outcome of Leishmania donovani development in P. argentipes and their transmissibility to the vertebrate host.
Clinical correlates in an experimental model of repetitive mild brain injury

Although there is growing awareness of the long‐term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long‐term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies.
Broadly altered expression of the mRNA isoforms of FE65, a facilitator of beta amyloidogenesis, in Alzheimer cerebellum and other brain regions

FE65 is a key “adapter” protein that links a multiprotein complex to an intracellular domain of β‐amyloid precursor protein (βPP). Its overexpression modulates the trafficking of βPP and facilitates the generation of β‐amyloid (Aβ). FE65 is predominantly expressed in brain tissues. An exon 9‐inclusive isoform is exclusively expressed in neurons, and an exon 9‐exclusive isoform is only expressed in non‐neuronal cells. We quantitated the two isoforms in middle temporal cortex, middle frontal cortex, cerebellar cortex and caudate nucleus of 17 Alzheimer disease (AD) patients, 12 normal controls and 9 non‐AD neurodegenerative disease controls by reverse transcription‐competitive polymerase chain reaction (RT‐cPCR). Expression of the two isoforms was significantly and differentially altered, with a 30–57% decrease in levels of the neuronal form (P < 0.05–0.002) and a 73–135% increase in levels of non‐neuronal form (P < 0.02–0.001), in the temporal and frontal cortex of AD brains. These alterations presumably reflect advanced neurodegenerative processes of these regions. Surprisingly, expression of both isoforms was significantly up‐regulated by 42–66% in the cerebellar cortex and caudate nucleus of AD brains when compared to normal brains (P < 0.05–0.005). Diffuse Aβ‐positive plaques were observed in the cerebellum of these AD subjects but not in the normal controls. Selective up‐regulation of only the FE65 neuronal isoform was seen in the cerebellar cortex in association with other neurodegenerative diseases (largely Parkinson's disease). Because FE65 modulates trafficking of βPP toward the production of Aβ, the up‐regulation of FE65 in AD cerebellum may be relevant to the genesis of diffuse plaques. Thus, early biochemical alterations in AD, not complicated by advanced pathology, may be beneficially investigated in the less‐affected regions of the brain, such as the cerebellum. J. Neurosci. Res. 60:73–86, 2000 © 2000 Wiley‐Liss, Inc.
Greater Expansion of IFN- γ ﹣ CD4 + NKT Cells in HIV-1 Compared with HIV-2-Infected Subjects with Preserved CD4 + T Cell Counts

Context: Human Natural Killer T cells are T lymphocytes that express an invariant αβ T cells receptors and NK cells receptors. They regulate innate and adaptive immune response but are susceptible to HIV-1 infection. Objective: We compare the frequency and the activity of NKT cells in HIV-1 and HIV-2 infected individuals with CD4+ counts greater than 500/mm3 using flow cytometry after overnight stimulation with phytohemagglutinin (PHA). Results: The frequency of NKT cells was similar between both groups and also to sero-negative control subjects. There were also no significant differences in the proportions of total NKT cells and the CD4+ NKT subset that secreted interferon gamma (IFN-γ) after polyclonal stimulation. However, there was a significantly higher frequency of IFN-γ﹣ CD4+ NKT cells in HIV-1-infected compared with HIV-2 infected subjects (p = 0.043). Conclusion: These data suggest there is no relationship between the functional activity of NKT cell subsets and the total NKT cell population in HIV infection. The expansion of IFN-γ﹣ CD4+ NKT cells in HIV-1 infection may serve as target for viral infection and may eventually result in their depletion during chronic infection.
Preclinical Characterization of OSI-027, a Potent and Selective Inhibitor of mTORC1 and mTORC2: Distinct from Rapamycin

The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC50 values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K–AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. Mol Cancer Ther; 10(8); 1394–406. ©2011 AACR.
Effects of abscisic Acid and ethylene on the gibberellic Acid-induced synthesis of alpha-amylase by isolated wheat aleurone layers.

Gibberellic acid-induced alpha-amylase synthesis in wheat aleurone layers (Triticum aestivum L. var Potam S-70) escaped from transcriptional control 30 h after addition of the hormone, as evidenced by the tissue's loss of susceptibility to cordycepin. Abscisic acid inhibited the accumulation of alpha-amylase activity when added to the tissue during this cordycepin-insensitive phase of enzyme induction. alpha-Amylase synthesis was not restored by the addition of cordycepin, indicating that the response to abscisic acid was not dependent upon the continuous synthesis of a short lived RNA. When ethylene was added simultaneously or some time after abscisic acid, the accumulation of alpha-amylase activity was sustained or quickly restored. The loss of susceptibility to cordycepin was completely prevented when aleurone layers were incubated with a combination of gibberellic and abscisic acids from the start of the induction period. This effect of abscisic acid was not reversed by ethylene. On the basis of these observations, it is suggested that abscisic acid inhibits both the transcription and translation of alpha-amylase mRNA, and that only the latter site of action is susceptible to reversal by ethylene.The rate of incorporation of [methyl-(14)C]choline into phospholipids was also inhibited by abscisic acid. Ethylene reversed this effect. The effects of abscisic acid and ethylene on phospholipid synthesis were not dependent upon the presence of gibberellic acid. No direct relationship was found between the control of alpha-amylase synthesis and membrane formation by abscisic acid and ethylene.
A dual role for the βPS integrin myospheroid in mediating Drosophila embryonic macrophage migration

Summary Throughout embryonic development, macrophages not only act as the first line of defence against infection but also help to sculpt organs and tissues of the embryo by removing dead cells and secreting extracellular matrix components. Key to their function is the ability of embryonic macrophages to migrate and disperse throughout the embryo. Despite these important developmental functions, little is known about the molecular mechanisms underlying embryonic macrophage migration in vivo. Integrins are key regulators of many of the adult macrophage responses, but their role in embryonic macrophages remains poorly characterized. Here, we have used Drosophila macrophages (haemocytes) as a model system to address the role of integrins during embryonic macrophage dispersal in vivo. We show that the main &bgr;PS integrin, myospheroid, affects haemocyte migration in two ways; by shaping the three-dimensional environment in which haemocytes migrate and by regulating the migration of haemocytes themselves. Live imaging revealed a requirement for myospheroid within haemocytes to coordinate the microtubule and actin dynamics, and to enable haemocyte developmental dispersal, contact repulsion and inflammatory migration towards wounds.
Evolution of vertebrate rod and cone phototransduction genes

Vertebrate cones and rods in several cases use separate but related components for their signal transduction (opsins, G-proteins, ion channels, etc.). Some of these proteins are also used differentially in other cell types in the retina. Because cones, rods and other retinal cell types originated in early vertebrate evolution, it is of interest to see if their specific genes arose in the extensive gene duplications that took place in the ancestor of the jawed vertebrates (gnathostomes) by two tetraploidizations (genome doublings). The ancestor of teleost fishes subsequently underwent a third tetraploidization. Our previously reported analyses showed that several gene families in the vertebrate visual phototransduction cascade received new members in the basal tetraploidizations. We here expand these data with studies of additional gene families and vertebrate species. We conclude that no less than 10 of the 13 studied phototransduction gene families received additional members in the two basal vertebrate tetraploidizations. Also the remaining three families seem to have undergone duplications during the same time period but it is unclear if this happened as a result of the tetraploidizations. The implications of the many early vertebrate gene duplications for functional specialization of specific retinal cell types, particularly cones and rods, are discussed.
FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

The accurate prediction, at a pre-dementia stage of Alzheimer’s disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment. We are indebted to Ms C. Lalevée, Ms P. Piolino, Dr F. Le Doze, Ms M.H. Noël, Ms M.C. Onfroy, Mr D. Luet, Mr O. Tirel, Ms A. Blondel, Ms C. Giry, Mr A. Traifi-Delarue and Mrs F. Leblond for their help in this study. This work was supported by INSERM U.320, Ministère de la Santé (PHRC, Principal Investigator: J-C Baron), Ministère de l’éducation nationale, and the Fondation France-Alzheimer.
Thioredoxin Reductase Linked to Cytoskeleton by Focal Adhesion Kinase Reverses Actin S-Nitrosylation and Restores Neutrophil β2 Integrin Function*

Background: Hyperbaric oxygen inhibits neutrophil β2 integrin adherence, but mechanisms for reversal are unclear. Results: Thioredoxin reductase reverses cytoskeletal changes due to hyperoxia when kept in proximity to short filamentous actin by focal adhesion kinase. Conclusion: Cell activation causes sequential protein associations with actin to restore integrin adherence function. Significance: Intermittent hyperoxia can have benefits, and results show why it does not concomitantly inhibit neutrophil antibacterial functions. The investigation goal was to identify mechanisms for reversal of actin S-nitrosylation in neutrophils after exposure to high oxygen partial pressures. Prior work has shown that hyperoxia causes S-nitrosylated actin (SNO-actin) formation, which mediates β2 integrin dysfunction, and these changes can be reversed by formylmethionylleucylphenylalanine or 8-bromo-cyclic GMP. Herein we show that thioredoxin reductase (TrxR) is responsible for actin denitrosylation. Approximately 80% of cellular TrxR is localized to the cytosol, divided between the G-actin and short filamentous actin (sF-actin) fractions based on Triton solubility of cell lysates. TrxR linkage to sF-actin requires focal adhesion kinase (FAK) based on immunoprecipitation studies. S-Nitrosylation accelerates actin filament turnover (by mechanisms described previously (Thom, S. R., Bhopale, V. M., Yang, M., Bogush, M., Huang, S., and Milovanova, T. (2011) Neutrophil β2 integrin inhibition by enhanced interactions of vasodilator stimulated phosphoprotein with S-nitrosylated actin. J. Biol. Chem. 286, 32854–32865), which causes FAK to disassociate from sF-actin. TrxR subsequently dissociates from FAK, and the physical separation from actin impedes denitrosylation. If SNO-actin is photochemically reduced with UV light or if actin filament turnover is impeded by incubations with cytochalasin D, latrunculin B, 8-bromo-cGMP, or formylmethionylleucylphenylalanine, FAK and TrxR reassociate with sF-actin and cause SNO-actin removal. FAK-TrxR association can also be demonstrated using isolated enzymes in ex vivo preparations. Uniquely, the FAK kinase domain is the site of TrxR linkage. We conclude that through its scaffold function, FAK influences TrxR activity and actin S-nitrosylation.