Miracle-dz/UniFAR-FTUs huggingface dataset:
Cyclic Nucleotide Control of Microtubule Dynamics for Axon Guidance

Graded distribution of intracellular second messengers, such as Ca2+ and cyclic nucleotides, mediates directional cell migration, including axon navigational responses to extracellular guidance cues, in the developing nervous system. Elevated concentrations of cAMP or cGMP on one side of the neuronal growth cone induce its attractive or repulsive turning, respectively. Although effector processes downstream of Ca2+ have been extensively studied, very little is known about the mechanisms that enable cyclic nucleotides to steer migrating cells. Here, we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance via modulating microtubule dynamics and membrane organelle transport. In embryonic chick dorsal root ganglion neurons in culture, contact of an extending microtubule with the growth cone leading edge induces localized membrane protrusion at the site of microtubule contact. Such a contact-induced protrusion requires exocytosis of vesicle-associated membrane protein 7 (VAMP7)-positive vesicles that have been transported centrifugally along the microtubule. We found that the two cyclic nucleotides counteractively regulate the frequency of microtubule contacts and targeted delivery of VAMP7 vesicles: cAMP stimulates and cGMP inhibits these events, thereby steering the growth cone in the opposite directions. By contrast, Ca2+ signals elicit no detectable change in either microtubule contacts or VAMP7 vesicle delivery during Ca2+-induced growth cone turning. Our findings clearly demonstrate growth cone steering machinery downstream of cyclic nucleotide signaling and highlight a crucial role of dynamic microtubules in leading-edge protrusion for cell chemotaxis. SIGNIFICANCE STATEMENT Developing neurons can extend long axons toward their postsynaptic targets. The tip of each axon, called the growth cone, recognizes extracellular guidance cues and navigates the axon along the correct path. Here we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance through localized regulation of microtubule dynamics and resulting recruitment of specific populations of membrane vesicles to the growth cone's leading edge. Remarkably, cAMP stimulates microtubule growth and membrane protrusion, whereas cGMP promotes microtubule retraction and membrane senescence, explaining the opposite directional polarities of growth cone turning induced by these cyclic nucleotides. This study reveals a novel microtubule-based mechanism through which cyclic nucleotides polarize the growth cone steering machinery for bidirectional axon guidance.
An Item-Oriented Algorithm on Cold-Start Problem in Recommendation System

Recommending new items is an important, yet challenging problem due to the lack of preference history for the new items. To handle this problem, the existing system uses the popular core techniques like collaborative filtering, content-based filtering and combinations of these. In this paper, we propose a market-based approach for seeding recommendations for new items in which new items will reach the audience quickest. To support this approach we purposed the algorithm that match the new item specification (features) with the existing item and identify whether these features are available in existing item sets or not. The proposed system identifies the user opinion on new item feature those are available in existing item set and generates the quality report of newly launched item (which is not purchased yet).
Enhanced operational stability of the up-conversion fluorescence in films of palladium-porphyrin end-capped poly(pentaphenylene).

The phenomenon of up-conversion, that is, the generation of higher-energy photons by simultaneous or sequential absorption of two or more photons, with lower energy, is mostly associated with the use of relatively high light intensities available from pulsed lasers. In organic systems, up-conversion fluorescence has also been described as a product of bimolecular processes in which the mechanism of triplet–triplet annihilation plays a prominent role. In our previous work, we demonstrated photon up-conversion in films containing two active components—metallated porphyrin macrocycles (MOEP) in a matrix of a polyfluorene (PF). The so-excited up-conversion fluorescence emission of the matrix polymer occurs at relatively low intensity and under continuous wave (cw) optical excitation. The method was successfully extended to a series of blue-emitting polymer matrices. A general advantage of the systems with more than one active component is the possibility to optimise each one of them independently. The major challenge is the optimisation and stability of the component distribution in the system. The up-conversion efficiency and operational stability of the emitting system is limited by both exand intrinsic factors. The extrinsic factors include the concentration of oxygen—either adsorbed in the film during the spin-coating process or permeated through the film surface over the entire period of optical testing of the sample. Oxygen decreases drastically the life time of the excited triplet state in the dopant molecule and hence the efficiency of the up-conversion process. Preparation and encapsulation of the sample in an inert atmosphere can control the concentration of oxygen. However, the control of the intrinsic parameters that decrease the up-conversion efficiency of the sample during operation is more challenging. In samples blended with dopant molecules, phase separation between the active polymer matrix and the dopant molecules occurs during the operation mostly because of the local in-
Photoluminescence intensity ratio of Eu‐conjugated lactates—A simple optical imaging technique for biomarker analysis for critical diseases

Instant measurement of elevated biomarkers such as lactic acid offers the most promising approaches for early treatment and prevention of many critical diseases including cardiac arrest, stroke, septic shock, trauma, liver dysfunction, as well as for monitoring lactic acid level during intense exercise. In the present study, a unique dependence of visible photoluminescence of Eu3+ ions resulting from 5D0 to 7FJ(J = 0,1,2,3,4) transitions, which can be exploited for rapid detection of biomarkers, both in vitro and ex vivo, has been reported. It is observed that the integrated intensity ratio of photoluminescence signals dominating at 591 and 616 nm originating from 5D0 to 7F2 and 5D0 to 7F1 transitions in Eu3+ ions can be used as a biosensing and bioimaging tool for detection of biomarkers released at disease states. The Eu3+ integrated photoluminescence intensity ratio approach reported herein for optical detection of lactates in blood serum, plasma and confocal imaging of brain tissues has very high potential for exploitation of this technique in both in vitro monitoring and in vivo bioimaging applications for the detection of biomarkers in various diseases states.
Activation of the Escherichia coli lacZ promoter by the Klebsiella aerogenes nitrogen assimilation control protein (NAC), a LysR family transcription factor

A chimeric promoter with the nitrogen assimilation control protein binding site from hutUp of Klebsiella aerogenes fused to the lacZ core promoter from Escherichia coli was built and cloned in a lacZ reporter plasmid. This construct showed a 14-fold increase of beta-galactosidase activity upon nitrogen limitation. Primer extension experiments showed that the nitrogen assimilation control protein activates lacZp1 in a position-dependent manner.
Impact d'un régime Western diet sur la plasticité du système nerveux entérique et répercussions fonctionnelles

Le systeme nerveux enterique (SNE) est un systeme nerveux integratif, innervant l'ensemble du tube digestif, qui controle les fonctions gastro-intestinales (GI). Certains facteurs nutritionnels peuvent moduler le phenotype du SNE et ainsi modifier les fonctions GI. Cependant, l'impact a long terme d'un desequilibre nutritionnel sur le SNE reste largement inconnu. Les objectifs de ce travail etaient donc 1) d'etudier les effets du regime « Western diet » (WD), caracterise par des apports nutritionnels excessifs en acides gras satures et en glucides simples, sur le SNE ainsi que les repercussions fonctionnelles associees et 2) d'identifier les mediateurs responsables de ces modifications. Dans la premiere partie de l'etude, nous avons mis en evidence que la consommation du regime WD pendant 12 semaines prevenait la perte des neurones myenteriques nitrergiques, associee a l'âge, observee dans l'antre des souris controles. Ces modifications du phenotype du SNE etaient associees a une augmentation de la transmission neuromusculaire nitrergique dans l'antre et a une acceleration de la vidange gastrique. De plus, nous avons identifie la leptine et le GDNF comme les mediateurs impliques dans ces effets neuroprotecteurs du regime WD. Dans la seconde partie de l'etude, nous avons observe que le regime WD entrainait une diminution de la permeabilite paracellulaire, associee a une augmentation de l'expression de la proteine de jonction serree Claudine-1 et du peptide intestinal vasoactif (VIP) dans le jejunum. Cette etude identifie donc le SNE comme un nouvel acteur implique dans les modifications des fonctions GI induites par un regime WD.
Molecular Characterization of Oxysterol Binding to the Epstein-Barr Virus-induced Gene 2 (GPR183)

Background: EBI2 was recently deorphanized as the first oxysterol-activated receptor, but the binding mode remains unknown. Results: Mutational analysis showed that substitution of Arg-87, Tyr-112, Tyr-116, and Tyr-260 abolished agonist binding and EBI2 activation. Conclusion: Oxysterol binding is dependent on residues in TM-II, -III, and -VI. Significance: This is the first study to examine the binding mode of these novel 7TM receptor agonists. Oxysterols are oxygenated cholesterol derivates that are emerging as a physiologically important group of molecules. Although they regulate a range of cellular processes, only few oxysterol-binding effector proteins have been identified, and the knowledge of their binding mode is limited. Recently, the family of G protein-coupled seven transmembrane-spanning receptors (7TM receptors) was added to this group. Specifically, the Epstein-Barr virus-induced gene 2 (EBI2 or GPR183) was shown to be activated by several oxysterols, most potently by 7α,25-dihydroxycholesterol (7α,25-OHC). Nothing is known about the binding mode, however. Using mutational analysis, we identify here four key residues for 7α,25-OHC binding: Arg-87 in TM-II (position II:20/2.60), Tyr-112 and Tyr-116 (positions III:09/3.33 and III:13/3.37) in TM-III, and Tyr-260 in TM-VI (position VI:16/6.51). Substituting these residues with Ala and/or Phe results in a severe decrease in agonist binding and receptor activation. Docking simulations suggest that Tyr-116 interacts with the 3β-OH group in the agonist, Tyr-260 with the 7α-OH group, and Arg-87, either directly or indirectly, with the 25-OH group, although nearby residues likely also contribute. In addition, Tyr-112 is involved in 7α,25-OHC binding but via hydrophobic interactions. Finally, we show that II:20/2.60 constitutes an important residue for ligand binding in receptors carrying a positively charged residue at this position. This group is dominated by lipid- and nucleotide-activated receptors, here exemplified by the CysLTs, P2Y12, and P2Y14. In conclusion, we present the first molecular characterization of oxysterol binding to a 7TM receptor and identify position II:20/2.60 as a generally important residue for ligand binding in certain 7TM receptors.
Physiology of the European brown bear (Ursus arctos arctos)

Although the American black (Ursus americanus) and American brown (grizzly) (Ursus arctos horribilis) bears have been the subjects of intensive physiological research, very little so far, has been done to understand the physiology of the European brown bear (Ursus arctos arctos). In our laboratory the research on the physiology of European brown bears started 10 years ago. Between 1987 and 1997, the seasonal changes in physiological indicators such as body temperature (Tb) and blood chemistry were studied in 12 bears under captive conditions in the Zoological Garden of the Department of Biology, University of Oulu, Finland. Changes in the Tb were measured either by using telemetric transmitters or dataloggers implanted into the abdominal cavity under anesthesia. The results show that the Tb decreases during the winter sleep to 3–5°C below the normal level or 37.0–37.5°C. Our bears only slept for just over three months per winter. The winter sleep started in late November/early December and ended in late February/early March. Our results do not support the theory of universal hibernation induction. Plasma from a winter-sleeping bear after injection either into Djungarian hamster (Phodopus sungorus) or laboratory rat did not affect body temperature or diurnal activity of the recipient. The urea concentration during the denning period is only half of that observed in the summer. This decrease during the denning period is in agreement with studies performed on American black and grizzly bears. In sharp contrast to earlier studies performed on the American black bear, our results reveal increases and decreases in the concentration of amino acids supporting the view that the denning bear may be even able to synthesize essential amino acids. The analysis of the total plasma fatty acids show that there may be a trend towards a greater need of unsaturated fatty acids in the denning bear as is the case of true hibernators.
Increases in disturbance and reductions in habitat size interact to suppress predator body size

Food webs are strongly size‐structured so will be vulnerable to changes in environmental factors that affect large predators. However, mechanistic understanding of environmental controls of top predator size is poorly developed. We used streams to investigate how predator body size is altered by three fundamental climate change stressors: reductions in habitat size, increases in disturbance and warmer temperatures. Using new survey data from 74 streams, we showed that habitat size and disturbance were the most important stressors influencing predator body size. A synergistic interaction between that habitat size and disturbance due to flooding meant the sizes of predatory fishes peaked in large, benign habitats and their body size decreased as habitats became either smaller or harsher. These patterns were supported by experiments indicating that habitat‐size reductions and increased flood disturbance decreased both the abundance and biomass of large predators. This research indicates that interacting climate change stressors can influence predator body size, resulting in smaller predators than would be predicted from examining an environmental factor in isolation. Thus, climate‐induced changes to key interacting environmental factors are likely to have synergistic impacts on predator body size which, because of their influence on the strength of biological interactions, will have far‐reaching effects on food‐web responses to global environmental change.
Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones.

1. Whole‐cell patch‐clamp techniques were used to record the excitatory postsynaptic current (EPSC) in a cultured mouse hippocampal neurone that resulted from electrical stimulation of another neurone in the cell culture. 2. L‐Glutamate (less than 1 microM) reversibly depressed the EPSC amplitude in 67% of the synapses tested. The average amplitude reduction was 40%. The depression by glutamate was not blocked by extracellular magnesium (0.8 mM) or 2‐amino‐5‐phosphonovaleric acid (AP5, 100 microM), indicating that N‐methyl‐D‐aspartate (NMDA) receptors were not involved. 3. The phosphonic derivative of glutamate, L‐2‐amino‐4‐phosphonobutyrate (L‐AP4), also depressed the EPSC amplitude. Neither glutamate nor L‐AP4 induced any detectable inward current at concentrations which produced a potent depression of the EPSC. Statistical analysis of the amplitude fluctuations of evoked synaptic currents showed that the depression induced by both glutamate and L‐AP4 was due to a decrease in the probability of synaptic release, confirming a presynaptic site of action. 4. Kainate and quisqualate also depressed excitatory synaptic transmission, but this action was related to the postsynaptic inward current that they induced. Statistical analysis showed that this action was consistent with a purely postsynaptic site of action. 5. Paired EPSCs separated by 20 ms showed either depression or potentiation of the second synaptic response. There was a strong correlation between those EPSCs which exhibited paired pulse depression and those depressed by glutamate application. 6. gamma‐Aminobutyric acid (GABA) and baclofen also depressed excitatory synaptic transmission. This depression was not blocked by picrotoxin (100 microM). GABA (10 microM) was effective in 85% of cell pairs tested, while baclofen (5 microM) depressed every EPSC tested. A presynaptic site of action for both substances was indicated by the statistical analysis. 7. The results indicate that both glutamate and GABA suppress excitatory synaptic transmission by an action at presynaptic sites. The glutamate‐induced depression may result from activation of a distinct excitatory amino acid receptor for which L‐AP4 is a specific agonist.
Human and rodent MaxiK channel beta-subunit genes: cloning and characterization.

Voltage- and Ca2+-sensitive K+ (MaxiK) channels play key roles in controlling neuronal excitability and vascular tone. We cloned and analyzed human and rodent genes for the modulatory beta subunit, KCNMB1. The human and mouse beta-subunit genes are approximately 11 and approximately 9 kb in length, respectively, and have a four exon-three intron structure. Primer extension assay localized the transcription initiation site at 442 (human) or 440 (mouse) bp upstream of the translation initiation codon, agreeing with the transcript size in Northern blots. Both genes have a TATA-less putative promoter region, with a transcription initiator-like region, and motifs characteristic of regulated promoters, including muscle-specific enhancing factors-1 and -2. Consistent with a tissue-specific expression of KCNMB1, regulated at the transcriptional level, beta-subunit transcripts are abundant in smooth muscle and heart, but scarce in lymphatic tissues, brain, and liver. Expressed rat and mouse beta subunits increase the apparent Ca2+ sensitivity of the human MaxiK channel alpha subunit.
Telomere length in myelodysplastic syndromes

We have studied telomere length in the bone marrow cells or the granulocyte and lymphocyte cell fractions of 54 patients with myelodysplastic syndromes (MDS) by Southern blot hybridization using the (TTAGGG)4 probe. The average telomere length expressed as the peak telomere repeat array (TRA) in the peripheral blood, or bone marrow samples obtained from a group of 21 healthy age‐matched controls (26–89 years old, mean age 55), ranged between 7.5 and 9.5 kb (mean peak TRA 8.6 kb). Twenty‐four patients with refractory anemia (RA) were studied; 10/24 (42%) had telomere reduction (<7.5 kb) relative to age‐matched controls and the mean peak TRA was 7.5 kb (range 4.0–9.0 kb). Eleven patients with RA with excess blasts (RAEB) were studied; 5/11 (45%) had reduced telomeres relative to age‐matched controls and the mean peak TRA was 7.1 kb (range 5.0–9.0 kb). Eighteen patients with MDS in transformation to AML, comprising 15 with RAEB in transformation (RAEBt) and 3 with CMML in transformation (CMMLt), were also studied. Thirteen of eighteen patients (72%) had telomere reduction relative to age‐matched controls and the mean peak TRA was 6.1 kb (range 3.5–9.0 kb). Thirty‐six patients included in the study had either a normal karyotype or a simple karyotype (1 karyotypic change) and 20/36 (55%) of these had telomere reduction and the mean peak TRA was 7.1 kb (range 4.3–9.0 kb); 8 patients had a complex karyotype (3 or more karyotypic changes) and 5/8 (62%) of these had telomere reduction and the mean peak TRA was 6.1 kb (range 3.5–9.0 kb). We conclude, firstly that there is heterogeneity of telomere length in MDS and that this is observed throughout the spectrum of FAB‐subtypes. Secondly, these data show that a marked reduction in telomere length in MDS if often associated with leukemic transformation and with the presence of complex karyotypic abnormalities. Am. J. Hematol. 56:266–271, 1997. © 1997 Wiley‐Liss, Inc.
Controle da artrite encefalite caprina através do uso de tecnologias reprodutivas aplicadas às fêmeas.

1Med. Vet. , D. Sc. , Pesquisadora da Embrapa Caprinos, Fazenda Três Lagoas, Estrada Sobral/Groaíras, Km 04, CEP 62010-970, C. Postal 145, Sobral/CE. E-mail: alice@cnpc.embrapa. br 2Med. Vet. , D. Sc. , Pesquisador da Embrapa Caprinos. E-mail: rizaldo@cnpc.embrapa. br 3Med. Vet. , D. Sc. , Professora da Universidade Federal de Minas Gerias. E-mail: aurora@vet.ufmg. br 4Estudante de Zootecnia, Universidade Estadual Vale do Acaraú. Bolsista da Embrapa Caprinos. E-mail:kelma_zoo@hotmail.com 5Med. Vet. , D. Sc. , Pesquisador da Embrapa Caprinos. E-mail: diones@cnpc.embrapa. br Comunicado
Adenoviruses in faeces of children with acute gastroenteritis in Rio De Janeiro, Brazil

Faeces from 746 children less than 5 years old with acute gastroenteritis were screened for the presence of adenovirus particles or antigens by immunoelectron microscopy (IEM) and enzyme immunoassay (EIA). Thirty‐five samples were positive by both IEM and EIA, two only by IEM, and two only by EIA, giving a total of 39 (5.2%) samples with positive results. Of these, 25 could be propagated in HEp2 cells and were neutralized by one of the antisera to adenovirus types 1 to 18. The remaining 14 samples could be propagated only in the 293 permanent line of human cells transformed by adenovirus type 5 DNA [Graham et al, 1977] and were not neutralized by antisera to adenovirus types 1 to 31. An EIA carried out by the antibody‐capture technique, using antiserum specific for “enteric” adenoviruses [Johansson et al, 1979], gave positive results with all isolates that could be propagated only in 293 cells and with none of those capable of growing in HEp2 cells.
Transcriptome asymmetry in synthetic and natural allotetraploid wheats, revealed by RNA-sequencing.

Allopolyploidization has occurred frequently within the Triticum-Aegilops complex which provides a suitable system to investigate how allopolyploidization shapes the expression patterns of duplicated homeologs. We have conducted transcriptome-profiling of leaves and young inflorescences in wild and domesticated tetraploid wheats, Triticum turgidum ssp. dicoccoides (BBAA) and ssp. durum (BBAA), an extracted tetraploid (BBAA), and a synthetic tetraploid (S(l) S(l) AA) wheat together with its diploid parents, Aegilops longissima (S(l) S(l) ) and Triticum urartu (AA). The two diploid species showed tissue-specific differences in genome-wide ortholog expression, which plays an important role in transcriptome shock-mediated homeolog expression rewiring and hence transcriptome asymmetry in the synthetic tetraploid. Further changes of homeolog expression apparently occurred in natural tetraploid wheats, which led to novel transcriptome asymmetry between the two subgenomes. In particular, our results showed that extremely biased homeolog expression can occur rapidly upon the allotetraploidzation and this trend is further enhanced in the course of domestication and evolution of polyploid wheats. Our results suggest that allopolyploidization is accompanied by distinct phases of homeolog expression changes, with parental legacy playing major roles in the immediate rewiring of homeolog expression upon allopolyploidization, while evolution and domestication under allotetraploidy drive further homeolog-expression changes toward re-established subgenome expression asymmetry.