Miracle-dz/UniFAR-FTUs huggingface dataset:
NMDA and β1-Adrenergic Receptors Differentially Signal Phosphorylation of Glutamate Receptor Type 1 in Area CA1 of Hippocampus

Glutamatergic synaptic transmission is mediated primarily through the AMPA-type glutamate receptor (AMPAR); the regulation of this receptor underlies many forms of synaptic plasticity. In particular, phosphorylation of GluR1, an AMPAR subunit, by PKA at serine 845 (S845) increases peak open channel probability and is permissive for both the synaptic expression of the receptor and NMDA-receptor (NMDAR)-dependent long-term potentiation (LTP). Robust NMDAR activation activates PKA as well as other signaling enzymes; however, we find that maximal NMDAR activation dephosphorylates GluR1 at the PKA site S845. Coincident inhibition of phosphatases blocks NMDAR-induced dephosphorylation of S845, but surprisingly does not promote PKA phosphorylation at this site. However, we find that phosphorylation of S845 is increased by the activation of a Gs-coupled receptor, the β1-adrenergic receptor. Interestingly, this divergent signaling occurs despite a more robust coupling of the NMDAR to cAMP generation. In addition, NMDAR activation plays a dominant role in S845 regulation, because activation of β1AR after NMDAR activation has no detectable effect on S845 phosphorylation. These data (1) demonstrate highly specific coupling between these receptors and this substrate, (2) provide an example of a substrate critical in NMDAR-dependent LTP that is incompletely regulated by the NMDAR, and (3) highlight the importance of identifying the physiological signals that regulate these critical synaptic substrates.
Endometrial connexin expression in the mare and pig: Evidence for the suppression of cell‐cell communication in uterine luminal epithelium

This investigation examines the relationship between implantation strategy and gap junction protein expression in uterine endometrium. The pattern of gap junction and connexin protein expression was analyzed in porcine and equine endometrium from cycling and pregnant animals using electron microscopy and immunocytochemistry. Functional analysis of cell‐cell communication was also monitored by laser cytometry in primary cultures of endometrial epithelial cells. Gap junctions were detected in endometrial stroma of cycling and pregnant animals, which was correlated with immunoreactive Cx43 within stromal fibroblasts and vascular elements. No Cx26, Cx32, or Cx43 immunostaining was detected in luminal endometrial epithelium in either the mare or the pig at any stage of the estrous cycle or pregnancy. In contrast, endometrial glands of the mare exhibited a spatiotemporal pattern of Cx43 expression in the apicolateral plasma membrane which, when present, colocalized with the tight junction–associated protein, ZO‐1. Uterine glandular Cx43 expression in mares was present from day 3 postovulation through day 14 of diestrus and until day 23 of pregnancy, whereas Cx43 was absent within uterine glands during seasonal anestrus, estrus, and after day 30 of pregnancy. Primary cultures of equine endometrial epithelial cells expressed both immunoreactive Cx43 and significant gap junction–mediated intercellular communication (GJIC) which was rapidly upregulated by 1.0 mM 8‐bromo‐cAMP or blocked with 1.0 mM octanol. No GJIC or connexin protein was detected in cultured porcine epithelial cells despite incubation with a variety of agents, including 8‐bromo‐cAMP, steroid hormones, retinoic acid, and/or prolactin.
Trends in probiotic research: A pathway towards relevance

C of PPG in early stages has the potential for the treatment of diabetes. Digestive enzyme inhibitors had recently taken the foremost attention of scientific community due to their unambiguious action on PPG. Identification and characterization of these inhibitors from natural resources to avoid side effects associated with synthetic drugs have become a common practice in last decade. Enzyme inhibition through some food sources or by food grade microorganism can have a dual advantage of combining nutritional approach with the pharmacological approach. Therefore, the present study was done to evaluate α-glucosidase inhibitory activity of food grade Lactobacillus spp. For this 54, α-glucosidase deficient lactobacilli isolates were screened for enzyme inhibition against α-glucosidase. Ten highest enzyme inhibitory isolates includes Lactobacillus salivarius (2), Lactobacillus plantarum (4), Lactobacillus fermentum (3) and Lactobacillus casei (1). After affirming their probiotic attributes Lactobacillus plantarum HAF 109 was further tested for control of PPG in sucrose loaded diabetic rat model. Feeding of probiotic fermented milk attenuated PPG levels by 17.2%, 28.2% and 41.3% at 0th day, 4th and 9th week in comparison to 8.5%, 21.2% and 62.3% of acarbose. The mechanism by which these results evolved are proposed to be a consequence of probiotic fermented milk inhibiting the metabolism of carbohydrates by the inhibition of brush border α-glucosidase in the small intestine, similar to that of acarbose. Nevertheless, the in vivo results suggest that the probiotic-fermented milk may exert potential anti-diabetic effect by suppressing PPG levels through the novel inhibition of intestinal α-glucosidase.
Levels of 4‐aminobiphenyl‐induced somatic H‐ras mutation in mouse liver DNA correlate with potential for liver tumor development

The utility of liver H‐ras codon 61 CAA to AAA mutant fraction as a biomarker of liver tumor development was investigated using neonatal male mice treated with 4‐aminobiphenyl (4‐ABP). Treatment with 0.1, 0.3, or 1.0 μmol 4‐ABP produced dose‐dependent increases in liver DNA adducts in B6C3F1 and C57BL/6N mice. Eight months after treatment with 0.3 μmol 4‐ABP or the DMSO vehicle, H‐ras codon 61 CAA to AAA mutant fraction was measured in liver DNA samples (n = 12) by allele‐specific competitive blocker‐polymerase chain reaction (ACB‐PCR). A significant increase in average mutant fraction was found in DNA of 4‐ABP‐treated mice, with an increase from 1.3 × 10−5 (control) to 44.9 × 10−5 (treated) in B6C3F1 mice and from 1.4 × 10−5 to 7.0 × 10−5 in C57BL/6N mice. Compared with C57BL/6N mutant fractions, B6C3F1 mutant fractions were more variable and included some particularly high mutant fractions, consistent with the more rapid development of liver foci expected in B6C3F1 mouse liver. Twelve months after treatment, liver tumors developed in 79.2% of 4‐ABP‐treated and 22.2% of control B6C3F1 mice; thus measurement of H‐ras mutant fraction correlated with subsequent tumor development. This study demonstrates that ACB‐PCR can directly measure background levels of somatic oncogene mutation and detect a carcinogen‐induced increase in such mutation. Published 2005 Wiley‐Liss, Inc.
Automated prostate cancer detection using T2-weighted and high-b-value diffusion-weighted magnetic resonance imaging.

PURPOSE The authors propose a computer-aided diagnosis (CAD) system for prostate cancer to aid in improving the accuracy, reproducibility, and standardization of multiparametric magnetic resonance imaging (MRI). METHODS The proposed system utilizes two MRI sequences [T2-weighted MRI and high-b-value (b = 2000 s/mm(2)) diffusion-weighted imaging (DWI)] and texture features based on local binary patterns. A three-stage feature selection method is employed to provide the most discriminative features. The authors included a total of 244 patients. Training the CAD system on 108 patients (78 MR-positive prostate cancers and 105 benign MR-positive lesions), two validation studies were retrospectively performed on 136 patients (68 MR-positive prostate cancers, 111 benign MR-positive lesions, and 117 MR-negative benign lesions). RESULTS In distinguishing cancer from MR-positive benign lesions, an area under receiver operating characteristic curve (AUC) of 0.83 [95% confidence interval (CI): 0.76-0.89] was achieved. For cancer vs MR-positive or MR-negative benign lesions, the authors obtained an AUC of 0.89 AUC (95% CI: 0.84-0.93). The performance of the CAD system was not dependent on the specific regions of the prostate, e.g., a peripheral zone or transition zone. Moreover, the CAD system outperformed other combinations of MRI sequences: T2W MRI, high-b-value DWI, and the standard apparent diffusion coefficient (ADC) map of DWI. CONCLUSIONS The novel CAD system is able to detect the discriminative texture features for cancer detection and localization and is a promising tool for improving the quality and efficiency of prostate cancer diagnosis.
The influence of nutritional state on shoal choice in zebrafish,Danio rerio


We investigated the mechanisms and functions of shoal choice in relation to nutritional state in the zebrafish. Single fish that had been well fed or food deprived for 2 days were presented with a choice between two stimulus shoals. Food-deprived test fish showed a significant preference for well-fed stimulus fish over food-deprived ones whereas well-fed test fish did not exhibit any significant preference. Subsequent experiments showed that food-deprived test fish had a significantly higher foraging success in shoals consisting of well-fed individuals than in ones that comprised food-deprived fish. No difference in the locomotory behaviour of food-deprived and well-fed stimulus fish was found with respect to the proportion of time spent swimming (as opposed to being motionless), the proportion of time spent in the upper part of the test tank and the number of sharp turns. However, body weight, stomach width (measured directly behind the pectoral girdle) and ventro-dorsal height significantly decreased over a 48-h food-deprivation period. The potential use of the latter factors for the recognition of food-deprived individuals is discussed. Copyright 1999 The Association for the Study of Animal Behaviour.
Giant papillary conjunctivitis

Purpose of reviewDespite shorter replacement intervals and new lens materials, giant papillary conjunctivitis still limits the ability of some patients to wear contact lenses. Recent findingsRecent research has elucidated many new mediators of inflammation. The presence of chemokines and cytokines such as IL-8, IL-6, IL-11, macrophage inflammatory protein-δ, tissue inhibitor of metalloproteinases-2 macrophage–colony stimulating factor and monokine-induced gamma interferon, eotaxin, pulmonary and activation-regulated CC chemokines have been shown to be elevated in patients with giant papillary conjunctivitis. In addition, M cells and B lymphocytes have been hypothesized to play a role in the pathogenesis of giant papillary conjunctivitis. SummaryThe pathophysiology of giant papillary conjunctivitis is complicated with both immune and mechanical mechanisms playing a role in the development of this condition; understanding these mechanisms is important in both treatment and prevention of giant papillary conjunctivitis.
Mutational Analysis of Ganglioside GM1-Binding Ability, Pentamer Formation, and Epitopes of Cholera Toxin B (CTB) Subunits and CTB/Heat-Labile Enterotoxin B Subunit Chimeras

ABSTRACT Variants of cholera toxin B subunit (CTB) were made by bisulfite- and oligonucleotide-directed mutagenesis of the ctxB gene. Variants were screened by a radial passive immune hemolysis assay (RPIHA) for loss of binding to sheep erythrocytes (SRBC). Variant CTBs were characterized for the formation of immunoreactive pentamers, the ability to bind ganglioside GM1 in vitro, and reactivity with a panel of monoclonal anti-CTB antibodies. Substitutions at eight positions (i.e., positions 22, 29, 36, 45, 64, 86, 93, and 100) greatly reduced the yield of immunoreactive CTB. RPIHA-negative substitution variants that formed immunoreactive pentamers were obtained for residues 12, 33, 36, 51, 52 + 54, 91, and 95. Tyrosine-12 was identified as a novel residue important for GM1 binding since, among all of the novel variants isolated with altered RPIHA phenotypes, only CTB with aspartate substituted for tyrosine at position 12 failed to bind significantly to ganglioside GM1 in vitro. In contrast, CTB variants with single substitutions for several other residues (Glu-51, Lys-91, and Ala-95) that participate in GM1 binding, based on the crystal structure of CTB and the oligosaccharide of GM1, were not appreciably altered in their ability to bind GM1 in vitro, even though they showed altered RPIHA phenotypes and did not bind to SRBC. Hybrid B genes made by fusing ctxB and the related Escherichia coli heat-labile enterotoxin eltB genes at codon 56 produced CTB variants that had 7 or 12 heat-labile enterotoxin B residue substitutions in the amino or carboxyl halves of the monomer, respectively, each of which which also bound GM1 as well as wild-type CTB. This collection of variant CTBs in which 47 of the 103 residues were substituted was used to map the epitopes of nine anti-CTB monoclonal antibodies (MAbs). Each MAb had a unique pattern of reactivity with the panel of CTB variants. Although no two of the epitopes recognized by different MAbs were identical, most of the single amino acid substitutions that altered the immunoreactivity of CTB affected more that one epitope. The tertiary structures of the epitopes of these anti-CTB MAbs are highly conformational and may involve structural elements both within and between CTB monomers. Substitution of valine for alanine at positions 10 and 46 had dramatic effects on the immunoreactivity of CTB, affecting epitopes recognized by eight or six MAbs, respectively.
How Adequate Is Your CV? Analyzing French CVs with ReaderBench

This study is aimed at presenting a new ReaderBench-based tool built to support candidates in increasing the quality of their CV for a job opening. Both the visual quality and the textual content are considered while also providing an overview and corresponding feedback for the entire CV. The presented CV analysis tool uses advanced Natural Language Processing techniques to interpret and understand the content from written texts, while also considering their visual traits. The study was performed on a collection of more than 50 CVs that were manually annotated as positive or negative in terms of their visual and content-oriented aspects. A statistical analysis based on more than 400 textual indices was performed on the training corpora in order to extract the traits that define a good commercial CV. The results enabled us to build an online tool accessible on our website that provides recommendations for CVs written in French language.
Limitation of myocardial injury with the potassium channel opener cromakalim and the nonvasoactive analog U-89,232: vascular vs. cardiac actions in vitro and in vivo.

Cromakalim has been shown to have anti-ischemic properties, but it also produces profound hypotension upon systemic administration. We hypothesized that U-89,232, a cromakalim analog, would reduce infarct size in an ischemia-reperfusion injury model without hemodynamic alteration. Twenty-four anesthetized, open chest New Zealand White rabbits were instrumented for occlusion of a marginal branch of the left coronary artery. All animals were subjected to coronary artery occlusion (30 min) and reperfusion (2 hr). Study animals received either cromakalim (20 micrograms/kg, i.v.) or U-89,232 (20 micrograms/kg, i.v.), which was given as a pretreatment 30 min before occlusion. Control animals (n = 10) received vehicle (10% dimethyl sulfoxide). At termination of the experiment, the necrotic area and the area at risk were determined with tetrazolium and India ink staining, and infarct size was calculated using planimetry. Treatment with cromakalim produced profound hypotension (greater than 30% decrease in mean arterial pressure), whereas U-89,232 had no such hemodynamic effect. With comparable areas at risk, infarct size (as a percent of risk area) in the control animals was 46.8 +/- 3.4%. Treatment with cromakalim or U-89,232 reduced infarct size to 33.1 +/- 4.4 and 24.4 +/- 4.0%, respectively (P < .05, both compared to control). In vitro studies demonstrate that although both of these compounds shorten the duration of the cardiac action potential, only cromakalim is active in vascular smooth muscle. We conclude that U-89,232 exhibits myoprotection without hypotension, and that its mechanism of action is most likely due to ability to affect cardiac electrophysiology.
L503F variant of carnitine/organic cation transporter 1 efficiently transports metformin and other biguanides

Carnitine/organic cation transporter 1 (OCTN1) is involved in gastrointestinal absorption and mitochondrial toxicity of biguanides in rodents, but its pharmacokinetic roles in humans are largely unknown. The purpose of this study was to clarify the transport activities of two major OCTN1 variants, L503F and I306T, for gabapentin and three biguanide drugs, metformin, buformin and phenformin.
EU Rules Beyond its Borders: The Policy‐Specific Effects of Transgovernmental Networks and EU Agencies in the European Neighbourhood

The European Union (EU) is increasingly involved in its rule advancement outside its borders through a dense net of transgovernmental networks. However, we know little about the effects of these networks. This article assesses the impact of transgovernmental networks across various policy domains in the European Neighbourhood Policy (ENP) region. Building on a novel longitudinal dataset, we demonstrate that the effects of transgovernmental networks vary across policy sectors. Policies marked by a higher degree of mutual interdependence exhibit greater positive change as a result of denser networks. Meanwhile, the involvement of EU agencies stimulates more intense technical co‐operation and broadens the range of policy areas covered. In doing so, EU agencies serve as bridges for the establishment of strong links between the EU and its neighbours.
Speech Pathology in Giant Cell Arteritis

This paper contains a review of the signs and symptoms of giant cell arteritis, especially speech and respiratory manifestations of the disease, which are demonstrated by a new case history. An elderly woman presented with speech that was falsetto, breathy, and marked by downward pitch breaks and phonation breaks. In addition, she had visual loss, headache, edema along the scalp and pharyngeal arteries, polymyalgia rheumatica, elevation of Westergren erythrocyte sedimentation rates, and positive arterial biopsy results. Her speech disorder recurred during an exacerbation. A vascular mechanism is proposed to explain her unusual speech, acute recurrence, and rapid recovery. This explanation (reversible ischemia of the laryngeal musculature) has been proposed by other authors in previous studies.
The Free Trade Area of Americas and the Regional Development in Brazil

The changes in a country’s economic structure generally don’t spread evenly through the geographic space. This is particularly true in large countries, where the concentration and specialization of the economic activity, the nature of the technology and its process, its position in relation to the consumption centers, and many other variables can affect the way through which an exogenous shock is internalized and absorbed by the national economy. The effects at regional level are hard to predict, given the complexity of the regional inter-relations. In this paper a static inter-regional applied general equilibrium model of Brazil is used to analyze the impacts of the Free Trade Area of Americas – FTAA formation upon the Brazilian economy, disaggregated at state level (27 regions). The model is derived from the ORANIGFR, calibrated with Brazilian data for the 1996 year, and the regional economies are modeled through a “top-down” approach. It is linked to the GTAP model according to a new methodology developed by Horridge and Ferreira Filho (2003) that allows the Brazilian inter-regional model to have results consistent with the global model. Three different scenarios are analyzed and compared: one where the same pattern of agreement observed in the North America Free Trade Area - NAFTA would result for FTAA, one where a linear 100% cut in all tariffs between the FTAA member countries apply, and another one where a 100% tariff cut between Mercosur and the European Union apply. The three scenarios imply different assumptions about the agriculture/industry products relative liberalization in trade, and have important differential impacts at regional level. These options and their meanings are discussed in the paper.
Three-dimensional tracking of motile bacteria near a solid planar surface.

Knowing how motile bacteria move near and along a solid surface is crucial to understanding such diverse phenomena as the migration of infectious bacteria along a catheter, biofilm growth, and the movement of bacteria through the pore spaces of saturated soil, a critical step in the in situ bioremediation of contaminated aquifers. In this study, a tracking microscope is used to record the three-dimensional motion of Escherichia coli near a planar glass surface. Data from the tracking microscope are analyzed to quantify the effects of bacteria-surface interactions on the swimming behavior of bacteria. The speed of cells approaching the surface is found to decrease in agreement with the mathematical model of Ramia et al. [Ramia, M. , Tullock, D. L. & Phan-Tien, N. (1993) Biophys J. 65,755-778], which represents the bacteria as spheres with a single polar flagellum rotating at a constant rate. The tendency of cells to swim adjacent to the surface is shown in computer-generated reproductions of cell traces. The attractive interaction potential between the cells and the solid surface is offered as one of several possible explanations for this tendency.
Balancing Requirements for Stability and Maneuverability in Cetaceans ]

SYNOPSIS. The morphological designs of animals represent a balance between stability for efficient locomotion and instability associated with maneuverability. Morphologies that deviate from designs associated with stability are highly maneuverable. Major features affecting maneuverability are positions of control surfaces and flexibility of the body. Within odontocete cetaceans (i.e., toothed whales), variation in body design affects stability and turning performance. Position of control surfaces (i.e., flippers, fin, flukes, peduncle) provides a generally stable design with respect to an arrow model. Destabilizing forces generated during swimming are balanced by dynamic stabilization due to the phase relationships of various body components. Cetaceans with flexible bodies and mobile flippers are able to turn tightly at low turning rates, whereas fast-swimming cetaceans with less flexibility and relatively immobile flippers sacrifice small turn radii for higher turning rates. In cetaceans, body and control surface mobility and placement appear to be associated with prey type and habitat. Flexibility and slow, precise maneuvering are found in cetaceans that inhabit more complex habitats, whereas high-speed maneuvers are used by cetaceans in the pelagic environment.