Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential Regulation of the Serotonin Transporter by Vesicle-Associated Membrane Protein 2 in Cells of Neuronal versus Non-Neuronal Origin

The serotonin transporter (SERT) is a key regulator of serotonergic signalling as it mediates the re-uptake of synaptic serotonin into nerve terminals, thereby terminating or modulating its signal. It is well-known that SERT regulation is a dynamic process orchestrated by a wide array of proteins and mechanisms. However, molecular details on possible coordinated regulation of SERT activity and 5-HT release are incomplete. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, interacts with SERT. This was documented in vitro, through GST pull-down assays, by co-immunoprecipitation experiments on heterologous cells and rat hippocampal synaptosomes, and with FRET analysis in live transfected HEK-293 MSR cells. The related isoforms VAMP1 and VAMP3 also physically interact with SERT. However, comparison of the three VAMP isoforms shows that only VAMP2 possesses a functionally distinct role in relation to SERT. VAMP2 influences 5-HT uptake, cell surface expression and the delivery rate of SERT to the plasma membrane differentially in HEK-293 MSR and PC12 cells. Moreover, siRNA-mediated knock-down of endogenous VAMP2 reduces 5-HT uptake in CAD cells stably expressing low levels of heterologous SERT. Deletion and mutant analysis suggest a role for the isoform specific C-terminal domain of VAMP2 in regulating SERT function. Our data identify a novel interaction between SERT and a synaptic vesicle protein and support a link between 5-HT release and re-uptake.
Colocalization and Redistribution of Dishevelled and Actin during WNT-Induced Mesenchymal Morphogenesis

Activation of the Wnt signaling pathway is important for induction of gene expression and cell morphogenesis throughout embryonic development. We examined the subcellular localization of dishevelled, the immediate downstream component from the Wnt receptor, in the embryonic mouse kidney. Using immunofluorescence staining, confocal microscopy, and coimmunoprecipitation experiments, we show that dishevelled associates with actin fibers and focal adhesion plaques in metanephric mesenchymal cells. Stimulation of Wnt signaling leads to profound changes in metanephric mesenchymal cell morphology, including disruption of the actin cytoskeleton, increased cell spreading, and increased karyokinesis. Upon activation of Wnt signaling, dishevelled also accumulates in and around the nucleus. Casein kinase Iε colocalizes with dishevelled along actin fibers and in the perinuclear region, whereas axin and GSK-3 are only present around the nucleus. These data indicate a branched Wnt signaling pathway comprising a canonical signal that targets the nucleus and gene expression, and another signal that targets the cytoskeleton and regulates cell morphogenesis.
Using Rapid Diagnostic Tests as a Source of Viral RNA for Dengue Serotyping by RT-PCR - A Novel Epidemiological Tool

Background Dengue virus infection causes major public health problems in tropical and subtropical areas. In many endemic areas, including the Lao PDR, inadequate access to laboratory facilities is a major obstacle to surveillance and study of dengue epidemiology. Filter paper is widely used for blood collection for subsequent laboratory testing for antibody and nucleic acid detection. For the first time, we demonstrate that dengue viral RNA can be extracted from dengue rapid diagnostic tests (RDT) and then submitted to real-time RT-PCR for serotyping. Methodology/Principal Findings We evaluated the Standard Diagnostics (SD) Bioline Dengue Duo RDT, a commonly used test in dengue endemic areas. First, using the QIAamp RNA kit, dengue RNA was purified from the sample pad of the NS1 RDT loaded with virus isolates of the four serotypes, then quantified by RT-PCR. We observed greater recovery of virus, with a mean of 27 times more RNA recovered from RDT, than from filter paper. Second, we evaluated dengue NS1 RDTs from patients at Mahosot Hospital, Vientiane, (99 patients) and from rural Salavan Provincial Hospital (362 patients). There was good agreement between dengue RT-PCR from NS1 RDT with RT-PCR performed on RNA extracted from patient sera, either using RDT loaded with blood (82.8% and 91.4%, in Vientiane and Salavan, respectively) or serum (91.9% and 93.9%). There was 100% concordance between RDT and serum RT-PCR of infecting dengue serotype. Conclusions/Significance Therefore, the collection of NS1 positive RDTs, which do not require cold storage, may be a novel approach for dengue serotyping by RT-PCR and offers promising prospects for the collection of epidemiological data from previously inaccessible tropical areas to aid surveillance and public health interventions.
Toric Ideals of Phylogenetic Invariants

Statistical models of evolution are algebraic varieties in the space of joint probability distributions on the leaf colorations of a phylogenetic tree. The phylogenetic invariants of a model are the polynomials which vanish on the variety. Several widely used models for biological sequences have transition matrices that can be diagonalized by means of the Fourier transform of an abelian group. Their phylogenetic invariants form a toric ideal in the Fourier coordinates. We determine generators and Gröbner bases for these toric ideals. For the Jukes-Cantor and Kimura models on a binary tree, our Gröbner bases consist of certain explicitly constructed polynomials of degree at most four.
Randomized Algorithms for Three Dimensional Protein Structures Alignment

The explosive growth of genetic sequence information has offered us comprehensive collections of the protein sequences found in many living organisms. The challenge of understanding these gene products has led to the development of functional proteomics methods, which collectively aim to imbue the raw sequence with biological understanding. Protein structure provides the opportunity to recognize homology that is undetectable by sequence comparison, and it represents a powerful means of discovering functions, yielding direct insight into the molecular mechanisms. Currently, there are several techniques available in attempting to find the optimal alignment of shared structural motifs between two proteins. In this paper, we propose novel algorithms for pairwise alignment of protein structures. Methods of locating suitable isometric transformations of one structure and aligning it to the other structure are addressed. Our methods allow sequence gaps of any length, reversal of chain direction, and free topological connectivity of atom sequences. Sequential connectivity can be imposed as an option. The method is fully automatic to identify structural resemblances and common structural cores accurately and sensitively, even in the presence of geometrical distortions.
Pressure Ulcers in Orthopaedics

&NA; Pressure ulcers can be a devastating complication in the care of orthopaedic patients. Their presence leads to increased morbidity, mortality, and cost of care. Therapy and rehabilitation cannot progress on a normal postoperative course in the patient with a pressure ulcer. Risk factors for the development of pressure ulcers include spinal cord injury, advanced age, and cognitive impairment. Several grading scales have been developed for the assessment of pressure ulcer. Frequent patient turning, close monitoring, and frequent skin checks are important factors in the prevention of pressure ulcer.
Morphological and biochemical responses of Oryza sativa L. (cultivar MR219) to ion beam irradiation

Heavy ion beam, which has emerged as a new mutagen in the mutation breeding of crops and ornamental plants, is expected to result in the induction of novel mutations. This study investigates the morphological and biochemical responses of Oryza sativa toward different doses of carbon ion beam irradiation. In this study, the dry seeds of O. sativa were irradiated at 0, 20, 40, 60, 80, 100, and 120 Gy, followed by in-vitro germination under controlled conditions. Morphological and biochemical studies were conducted to investigate the morphological and physiological responses of O. sativa towards ion beam irradiation. The study demonstrated that low doses (10 Gy) of ion beam have a stimulating effect on the height, root length, and fresh weight of the plantlets but not on the number of leaves. Meanwhile, doses higher than 10 Gy caused reductions in all the morphological parameters studied as compared to the control samples. The highest total soluble protein content [(2.11±0.47) mg/g FW] was observed in plantlets irradiated at 20 Gy. All irradiated plantlets were found to have 0.85% to 58.32% higher specific activity of peroxidase as compared to the control samples. The present study also revealed that low doses of ion beam (10 and 20 Gy) had negligible effect on the total chlorophyll content of O. sativa plantlets while 40 Gy had a stimulating effect on the chlorophyll content. Plantlets irradiated between 40 to 120 Gy were shown to be 0.38% to 9.98% higher in total soluble nitrogen content which, however, was not significantly different from the control samples. Carbon ion beam irradiation administered at low to moderate doses of 10 to 40 Gy may induce O. sativa mutants with superior characteristics.
Smoking in Asthma Is Associated with Elevated Levels of Corticosteroid Resistant Sputum Cytokines—An Exploratory Study

Background Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear. Objectives To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids. Methods Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform. Results Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers with asthma compared to never smokers with asthma. Conclusion Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.
Reaction and functionality of sulfuric and chromic acids over low density polyethylene for medical textiles: A comparative study

Low density polyethylene (LDPE) swollen in mixture of polar and non-polar solvents was subjected to sulfuric and chromic acids to promote durable hydrophilic and electrical properties. ATR-Fourier transforms infrared spectroscopy and elemental analysis of the treated LDPE depicts the reaction mechanism of both the acids over low density polyethylene in swollen condition. Both sulfuric and chromic acids promote in-depth modification of LDPE resulting in enhanced hydrophilicity and lower electrical resistivity of the polymer. FTIR spectra indicate formation of double bonds, sulfonic and carbonyl moieties. Contact angle goniometry indicates a 30o decrease in contact angle and Photo Luminescence Spectroscopy computes band gap decrease to 2.8eV. Comparative results suggest chromic acid as more influential functionalization agent for low density polyethylene at lower concentrations. Index Terms Low density polyethylene, mineral acids, reaction mechanism, hydrophilicity, band gap. ——————————  ——————————
In vivo 2H2O administration reveals impaired triglyceride storage in adipose tissue of insulin-resistant humans1

Indirect evidence suggests that impaired triglyceride storage in the subcutaneous fat depot contributes to the development of insulin resistance via lipotoxicity. We directly tested this hypothesis by measuring, in vivo, TG synthesis, de novo lipogenesis (DNL), adipocyte proliferation, and insulin suppression of lipolysis in subcutaneous adipose tissue of BMI-matched individuals classified as insulin resistant (IR) or insulin sensitive (IS). Nondiabetic, moderately obese subjects with BMI 25–35 kg/m2, classified as IR or IS by the modified insulin suppression test, consumed deuterated water (2H2O) for 4 weeks. Deuterium incorporation into glycerol, palmitate, and DNA indicated TG synthesis, DNL, and adipocyte proliferation, respectively. Net TG synthesis and DNL in adipose cells were significantly lower in IR as compared with IS subjects, whereas adipocyte proliferation did not differ significantly. Plasma FFAs measured during an insulin suppression test were 2.5-fold higher in IR subjects, indicating resistance to insulin suppression of lipolysis. Adipose TG synthesis correlated directly with DNL but not with proliferation. These results provide direct in vivo evidence for impaired TG storage in subcutaneous adipose tissue of IR as compared with IS. Relative inability to store TG in the subcutaneous depot may represent a mechanism contributing to the development of insulin resistance in the setting of obesity.
Glycolytic Metabolism of Neonatal Mononuclear Cells

Summary: The mononuclear cells of newborn infants compared to those of normal adults contain diminished activity of pyruvate kinase (PK) (14.9 ± 1.2 vs. 22.3 ± 1.3 μmol/1010 cells/min) and phosphoglycerate kinase (PGK) (195 ± 10 vs. 415 ± 19). These deficiencies are accentuated in the cells of premature infants (4.9 ± 0.5 and 71 ± 15, respectively) and are accompanied by reduced activity of adenylate kinase (AK) (14.8 ± 1.9 vs. 33.6 ± 2.6). The activities of AK and PGK in adult and neonatal mononuclear cells are stimulated by phytohemagglutinin (PHA). Although the PK activity of adult cells is stimulated by PHA, the PK activity of neonatal cells is not. Mononuclear cell glycolysis is stimulated by PHA in both adults and neonates. The mean lactate production of neonatal cells is slightly lower than it is in adult cells (93 vs. 110 μmol/1010 cells/hr, unstimulated, and 151 vs. 181, stimulated), but the differences are not statistically significant. The ATP content of neonatal cells (3.8 ± 0.4 μmoll 1010 cells) is reduced compared to adult values (6.0 ± 0.3). Lactate production is directly correlated with PK activity in adult and neonatal mononuclear cells. Neonatal mononuclear cell PK activity increases to adult levels during the first year of life.Speculation: Glycolytic metabolism of neonatal mononuclear cells differs from that observed in adult cells. Pyruvate kinase may play a critical role in the energy metabolism of immunocytes. The observed increase in mononuclear cell PK activity to adult values in the middle of the first year of life may suggest a correlation of PK activity with maturation of monocyte function.
T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice1

Multiple sclerosis (MS) is a chronic autoimmune disease triggered by unknown environmental factors in genetically susceptible hosts. MS risk was linked to high rates of cow milk protein (CMP) consumption, reminiscent of a similar association in autoimmune diabetes. A recent rodent study showed that immune responses to the CMP, butyrophilin, can lead to encephalitis through antigenic mimicry with myelin oligodendrocyte glycoprotein. In this study, we show abnormal T cell immunity to several other CMPs in MS patients comparable to that in diabetics. Limited epitope mapping with the milk protein BSA identified one specific epitope, BSA193, which was targeted by most MS but not diabetes patients. BSA193 was encephalitogenic in SJL/J mice subjected to a standard protocol for the induction of experimental autoimmune encephalitis. These data extend the possible, immunological basis for the association of MS risk, CMP, and CNS autoimmunity. To pinpoint the same peptide, BSA193, in encephalitis-prone humans and rodents may imply a common endogenous ligand, targeted through antigenic mimicry.
Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women.

BACKGROUND Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear. OBJECTIVE The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women. DESIGN Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase. RESULTS Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002). CONCLUSIONS Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.
Evolution of Speech Recognizer Agents by Artificial Life

A state or territory trivia game has a game board bearing a map or representation of a particular state or territory, and that representation is divided into eight color coded sections or regions. Each section represents a different region of the state or territory. On the sides of the board are smaller representations of the state or territory. These are used for the collection of game collection pieces. Game question and answer cards have eight questions relating to the history, geography, etc. of the respective regions of the state or territory, and the answers provided on the other side of the card. The card is arranged so that the answers cannot readily be seen as the question is being asked. The game begins with each player in the state capital or in some other predetermined city, and the player moves his or her piece a number of squares across the board in correspondence with the roll of a die or other randomizer. The object is to answer questions correctly while the transit piece occupies a city station earning a collection piece. The winner of the game is the first player to earn all eight collection pieces.
Development of Posterior Hypothalamic Neurons Enlightens a Switch in the Prosencephalic Basic Plan

In rats and mice, ascending and descending axons from neurons producing melanin-concentrating hormone (MCH) reach the cerebral cortex and spinal cord. However, these ascending and descending projections originate from distinct sub-populations expressing or not “Cocaine-and-Amphetamine-Regulated-Transcript” (CART) peptide. Using a BrdU approach, MCH cell bodies are among the very first generated in the hypothalamus, within a longitudinal cell cord made of earliest delaminating neuroblasts in the diencephalon and extending from the chiasmatic region to the ventral midbrain. This region also specifically expresses the regulatory genes Sonic hedgehog (Shh) and Nkx2.2. First MCH axons run through the tractus postopticus (tpoc) which gathers pioneer axons from the cell cord and courses parallel to the Shh/Nkx2.2 expression domain. Subsequently generated MCH neurons and ascending MCH axons differentiate while neurogenesis and mantle layer differentiation are generalized in the prosencephalon, including telencephalon. Ascending MCH axons follow dopaminergic axons of the mesotelencephalic tract, both being an initial component of the medial forebrain bundle (mfb). Netrin1 and Slit2 proteins that are involved in the establishment of the tpoc and mfb, respectively attract or repulse MCH axons. We conclude that first generated MCH neurons develop in a diencephalic segment of a longitudinal Shh/Nkx2.2 domain. This region can be seen as a prosencephalic segment of a medial neurogenic column extending from the chiasmatic region through the ventral neural tube. However, as the telencephalon expends, it exerts a trophic action and the mfb expands, inducing a switch in the longitudinal axial organization of the prosencephalon.
Effect of antisense oligodeoxynucleotides for ICAM‐1 on renal ischaemia–reperfusion injury in the anaesthetised rat

An antisense oligodeoxynucleotide (As‐ODN) to the 3′ untranslated region of the mRNA sequence expressing the intracellular adhesion molecule‐1 (ICAM‐1) was employed to determine ICAM‐1's role in renal ischaemia–reperfusion injury in the rat. Wistar‐Kyoto rats receiving i.v. either lipofectin–As‐ODN (As‐ODN group), lipofectin–reverse ODN (Rv‐ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post‐ischaemia period in the ischaemia control and Rv‐ODN groups, but was maintained in the As‐ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv‐ODN groups, but was below basal levels (20%) in the As‐ODN group. There was a three‐ to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse‐ODN groups but not in the As‐ODN treated group. The As‐ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM‐1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post‐ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM‐1. The possibility arises that the action of ICAM‐1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia–reperfusion injury.