Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Association of TRPC Channel Subunits in Rat Brain Synaptosomes* 210

TRPC genes encode a ubiquitous family of ion channel proteins responsible for Ca2+ influx following stimulation of G-protein-coupled membrane receptors linked to phospholipase C. These channels may be localized to large multimeric signaling complexes via association with PDZ-containing scaffolding proteins. Based on sequence homology, the TRPC channel family can be divided into two major subgroups: TRPC1, -C4, and -C5 and TRPC3, -C6, and -C7. Although TRPC channels are thought to be tetramers, the actual subunit composition remains unknown. To determine subunit arrangement, individual TRPC channel pairs were heterologously expressed in Sf9 insect cells and immunoprecipitated using affinity-purified rabbit polyclonal antibodies specific for each channel subtype. Reciprocal co-immunoprecipitations showed that TRPC1, -C4, and -C5 co-associate and that TRPC3, -C6, and -C7 co-associate but that cross-association between the two major subgroups does not occur. Additionally, the interaction between each TRPC channel and the PDZ-containing protein, INAD (protein responsible for theinactivation-no-after-potentialDrosophila mutant), was examined. TRPC1, -C4, and -C5 co-immunoprecipitated with INAD, whereas TRPC3, -C6, and -C7 did not. To define channel subunit interactions in vivo, immunoprecipitations were performed from isolated rat brain synaptosomal preparations. The results revealed that TRPC1, -C4, and -C5 co-associate and that TRPC3, -C6, and -C7 co-associate in both cortex and cerebellum but that cross-association between the two major subgroups does not occur. These results demonstrate that TRPC channels are present in nerve terminals and provide the first direct evidence for selective assembly of channel subunits in vivo.
Hypothyroidism Reduces Tricarboxylate Carrier Activity and Expression in Rat Liver Mitochondria by Reducing Nuclear Transcription Rate and Splicing Efficiency*

The tricarboxylate carrier (TCC), also known as citrate carrier, is an integral protein of the mitochondrial inner membrane. It is an essential component of the shuttle system by which mitochondrial acetyl-CoA, primer for both fatty acid and cholesterol synthesis, is transported into the cytosol, where lipogenesis occurs. The effect of hypothyroidism on the activity and expression of the hepatic mitochondrial TCC was investigated in this study. TCC activity was significantly decreased in hypothyroid rats as compared with euthyroid animals. This hormone deficiency effect was due to a reduction in the amount of carrier protein, which resulted from a proportionate decrease of the specific mRNA. Hypothyroidism did not influence TCC mRNA stability. On the other hand, nuclear run-on assay revealed that the transcriptional rate of TCC mRNA decreased by ∼40% in the nuclei from hypothyroid versus euthyroid rats. In addition, the ribonuclease protection assay showed that, in the nuclei of hypothyroid rats, the ratio of mature to precursor RNA decreased, indicating that the splicing of TCC RNA is affected. Furthermore, we found that the ratio of polyadenylated/unpolyadenylated TCC RNA as well as the length of the TCC RNA poly(A) tail were similar in both euthyroid and hypothyroid rats. Thus, the rate of formation of the TCC 3′-end is not altered in hypothyroidism. These results suggest that hypothyroidism affects TCC expression at both the transcriptional and post-transcriptional levels.
Molecular support for vicariance as a source of diversity in rainforest

The origin of high diversity in tropical rainforests is attributed to divergence amongst relatively mesic, late Pleistocene refuges. To test this hypothesis we analysed sequence variation within the mitochondrial DNA of populations of six rainforest-dwelling vertebrate species (one lizard and five birds) in the Wet Tropical rainforests of northeastern Australia. Vicariance among historical refuges was indicated by geographically congruent variation across a historical climatic barrier previously predicted by modelling. Sequence divergence across the barrier varied widely, being highest in species with lowest vagility and greatest restriction to rainforest. A high altitude, rainforest-restricted species was exceptional in lacking mtDNA variation. These data support the suggested role of vicariance in promoting evolutionary diversity in rainforests but also indicate variation in the timing of vicariance events, with most speciation or divergence events occurring well before the late Pleistocene. The relation between the amount of molecular divergence and current ecology suggests a sequence of isolation events, perhaps of increasing severity, occurring between the late Tertiary and the late Pleistocene.
Prospective, randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less.

PURPOSE The optimal management of lower pole renal calculi is controversial. We compared shock wave lithotripsy (SWL) and ureteroscopy (URS) for the treatment of patients with small lower pole stones in a prospective, randomized, multicenter trial. MATERIALS AND METHODS A total of 78 patients with 1 cm or less isolated lower pole stones were randomized to SWL or URS. The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months. Secondary outcome parameters were length of stay, complication rates, need for secondary procedures and patient derived quality of life measures. RESULTS A total of 67 patients randomized to SWL (32) or URS (35) completed treatment. The 2 groups were comparable with respect to age, sex, body mass index, side treated and stone surface area. Operative time was significantly shorter for SWL than URS (66 vs 90 minutes). At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35% and 50%, respectively (p not significant). Intraoperative complications occurred in 1 SWL case (unable to target stone) and in 7 URS cases (failed access in 5 and perforation in 2), while postoperative complications occurred in 7 SWL and 7 URS cases. Patient derived quality of life measures favored SWL. CONCLUSIONS This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi. However, SWL was associated with greater patient acceptance and shorter convalescence.
The age at onset in Multiple Sclerosis is associated with patient's prognosis.

BACKGROUND The causes of the individual differences in the rate of disability progression in multiple sclerosis (MS) are still not completely clear. According to the long-term prognosis of MS patients, the search for new valuable prognostic markers of "benign" or "malign" MS is necessary. OBJECTIVES Our aim was to assess the possible association of MS onset age with the disease disability progression rate in Slovak patients with MS. METHODS By the unique pattern of evaluation of disability progression rate using Multiple Sclerosis Severity Score (MSSS), each of 270 MS patients was defined as slow-progressing, mid-rate progressing or rapidly progressing. RESULTS We found a significant differences in the age at onset between MS patients with different rate of disability progression (p(K-W)<0,00005). The faster was a disability progression assessed by MSSS score, the higher was the MS onset age. CONCLUSION We showed for the first time in Central European Slovak population that MS onset age is an early marker that is in the positive correlation with disease disability progression rate, evaluated by MSSS score. We conclude that relapsing-remitting MS patients older at clinical onset have a higher risk of unfavorable prognosis (Tab. 2, Fig. 1, Ref. 21).
Role of Sphk1 in the malignant transformation of breast epithelial cells and breast cancer progression.

BACKGROUND The ojective of the following study is to investigate the role of sphingosine kinase 1 (Sphk1) in the malignant transformation of breast epithelial cells and breast cancer progression and its mechanism. MATERIALS AND METHODS Immunohistochemistry was performed to detect Sphk1 and E-cadherin (E-cad) in resected breast samples. Sphk1 was transfected in normal human breast epithelial cell line (MCF-10A) by Lentivirus and silenced in breast cancer cell line (MCF-7) using small interfering ribonucleic acid. The effect of tumor necrosis factor alpha (TNF-α) and/or N, N-dimethylsphingosine (DMS) on the Sphk1 and E-cad expression, MCF-10A cell proliferation and invasion was investigated. Real time-polymerase chain reaction and western-blot was used to detect messenger ribonucleic acid and protein. Cell counting kit-8 and transwell were used to measure cell proliferation and invasion. RESULTS Sphk1 was positive expression in 114 breast tumors (75.50%) but negative in fibroadenomas. The expression of E-cad and Sphk1 were negatively correlated and E-cad (-)/Sphk1 (+) carriers showed higher ratio of axillary lymph node metastasis than E-cad (+)/Sphk1 (-) carriers. Overexpression of Sphk1 in MCF-10A reduced E-cad expression and improved cell proliferation and invasion, but knockdown of Sphk1 in MCF-7 decreased cell proliferation and invasion. TNF-α increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E-cad expression, which could be blocked by DMS. TNF-α promoted MCF-10A cell proliferation and invasion. CONCLUSION Sphk1 plays an important role in the malignant transformation of breast epithelial cells and modulates breast cancer metastasis through the regulation of E-cad expression. TNF-α can up-regulate Sphk1 expression and reduce E-cad expression through Sphk1, which can be blocked by DMS. TNF-α/Sphk1/E-cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis.
Within-plant distribution of 1,4-benzoxazin-3-ones contributes to herbivore niche differentiation in maize.

Plant defences vary in space and time, which may translate into specific herbivore-foraging patterns and feeding niche differentiation. To date, little is known about the effect of secondary metabolite patterning on within-plant herbivore foraging. We investigated how variation in the major maize secondary metabolites, 1,4-benzoxazin-3-one derivatives (BXDs), affects the foraging behaviour of two leaf-chewing herbivores. BXD levels varied substantially within plants. Older leaves had higher levels of constitutive BXDs while younger leaves were consistently more inducible. These differences were observed independently of plant age, even though the concentrations of most BXDs declined markedly in older plants. Larvae of the well-adapted maize pest Spodoptera frugiperda preferred and grew better on young inducible leaves irrespective of plant age, while larvae of the generalist Spodoptera littoralis preferred and tended to grow better on old leaves. In BXD-free mutants, the differences in herbivore weight gain between old and young leaves were absent for both species, and leaf preferences of S. frugiperda were attenuated. In contrast, S. littoralis foraging patterns were not affected. In summary, our study shows that plant secondary metabolites differentially affect performance and foraging of adapted and non-adapted herbivores and thereby likely contribute to feeding niche differentiation.
The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine1

The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c+, CD8+ cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100+ cells or both CD8+ and CD11c+ cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.
Space vector modulation scheme for dual-bridge matrix converters using safe-commutation strategy

The proposed space-vector modulation scheme for dual-bridge matrix converters uses the principle of the indirect modulation strategy to calculate the duty cycles of the active vectors. On the other hand, zero-vectors duration and distribution within a switching cycle are elaborated such that the line side switches commutate at zero-current leading to safe commutation of the converter. The switching frequency (f s) can be expressed in terms of the line frequency (fl ) as: fs= 6*Ns*fl. For integer values of Ns, synchronization in time between the starting of each switching period and the position of the input current reference in the complex plane is performed. Compared to a previous modulation scheme, this strategy leads to reducing the harmonic distortion factor of the input current in particular case when Ns is odd. The effectiveness of the considered modulation scheme is emphasized using Matlab and Simulink software
Fitting the Nigeria Stock Market Return Series Using GARCH Models

This study investigated the performance of eleven competing time series GARCH models for fitting the rate of returns data, monthly observations on the index returns series of the market over the period of January 1996 to December 2015 was used. From the results obtained from the Log Likelihood (Log L), Schwarzs Bayesian Criterion (SBC) and the Akaike Information Criterion (AIC) values it was found that the models identified was not the same for the two periods (Training and Testing period) that is for Training period were CGARCH (1,1) and EGARCH (1,1) while for Testing period were ARCH (1) and GARCH (2,1). The two extreme classes of models are identified to represent the best and the worst groups respectively. The overall effect of this will tend to increase the volatility of the market returns. The paper therefore recommended that the Nigeria government should as a matter of urgency take appropriate positive measures through the security and exchange commission to regulate the market volatility so that the provided market index could be safely used as predictive index for measuring the performance of the firms and as a guide for investment purpose.
Association of Epstein-Barr virus early antigen diffuse component and virus-specified DNA polymerase activity

The role of Epstein-Barr virus (EBV) early antigen diffuse component (EA-D) and its relationship with EBV DNA polymerase in EBV genome-carrying cells are unclear, EBV-specified DNA polymerase was purified in a sequential manner from Raji cells treated with phorbol-12,13-dibutyrate and n-butyrate by phosphocellulose, DEAE-cellulose, double-stranded DNA-cellulose, and blue Sepharose column chromatography. Four polypeptides with molecular masses of 110,000, 100,000, 55,000, and 49,000 daltons were found to be associated with EBV-specified DNA polymerase activity. A monoclonal antibody which could neutralize the EBV DNA polymerase activity was prepared and found to recognize 55,000- and 49,000-dalton polypeptides. An EA-D monoclonal antibody, R3 (G. R. Pearson, V. Vorman, B. Chase, T. Sculley, M. Hummel, and E. Kieff, J. Virol. 47:183-201, 1983), was also able to recognize these same two polypeptides associated with EBV DNA polymerase activity. It was concluded that EBV EA-D polypeptides, as identified by R3 monoclonal antibody, are critical components of EBV DNA polymerase.
[Apoptosis of retinoic acid-resistant APL NB4-R1 cells induced by As4S4 and its molecular mechanism].

OBJECTIVE This study was to investigate the apoptosis-inducing effect of As(4)S(4) on the retinoic acid-resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanisms. METHODS The leukemia cell line NB4-R1 was cultured in vitro and divided into control group and treatment group. The apoptosis rate and cell cycle were detected by flow cytometry. The apoptotic DNA fragments were analyzed by agarose gel electrophoresis. The changes of BCL-2, BAX and Caspase-3 were determined by Western blot. RESULTS After NB4-R1 cells were treated with As(4)S(4)(25 µmol/L) for 0 h, 24 h, 48 h, the percentage of early apoptotic cells was obviously raised from 0% to 24.49% and 47.41%, the percentage of late apoptotic cells were elevated from 0.08% to 14.72% and 20.70%. Compared with control group, the DNA degradation revealed a characteristic DNA ladder during agarose gel electrophoresis after treatment for 24 h. The drug significantly induced an accumulation of the S phase cell population from 31.85% of the untreated cells to 42.53% and 55.12% treated with the different time whereas the NB4-R1 cells in G0/G1 phase decreased from 57.30% to 37.56% and 28.51%. As(4)S(4) could decrease the expression of BCL-2 and increase the level of BAX. Pro-caspase-3 could be cleaved into small active fragments under the apoptotic stimulation. CONCLUSION As(4)S(4) can efficiently induce NB4-R1 cell apoptosis, which may be related with the down-regulation of BCL-2 and the up-regulation of BAX, as well as the activation of Caspase-3.
[Effect of alendronate on interleukin-1beta induced chondrocytes of rat in vitro].

OBJECTIVE To investigate the feasibility of alendronate (ALN) in treating osteoarthritis (OA) by observing the effects of ALN on interleukin 1beta (IL-1beta) induced chondrocytes of rat in vitro. METHODS The chondrocytes of knee articular surface from 15 SD rats (1-month-old, female or male, weighing 100-150 g) were cultured. The chondrocytes were observed by inverted phase contrast microscope and identified by toluidine blue staining and HE staining. The third passage chondrocytes were divided into 3 groups: the chondrocytes were cultured with DMEM for 5 days in group A, with 10 ng/mL IL-1beta for 2 days and with DMEM for 3 days in group B, and with 10 ng/mL IL-1beta for 2 days and with 1 x 10(6) mol/L ALN for 3 days in group C. Immunocytochemistry and real-time PCR were performed to determine the expression levels of collagen type II (Col II), matrix metalloproteinase 13 (MMP-13), and p-catenin. RESULTS Toluidine blue staining proved that the cultured cells were chondrocytes. The integrated absorbency (IA) value of Col II in group C (10.290 7 +/- 0.499 2) was lower than that in group A (15.377 0 +/- 0.571 8) and higher than that in group B (5.463 2 +/- 0.450 4), showing significant differences (P < 0.05). The IA value of MMP-13 in group C (3.068 6 +/- 0.205 6) was significantly lower than that in group B (6.998 1 +/- 0.329 7, P < 0.05), but there was no significant difference when compared with group A (2.777 5 +/- 0.199 6, P > 0.05). The IA value of beta-catenin in group C (6.611 7 +/- 0.381 8) was lower than that in group B (11.799 9 +/- 0.348 7) and higher than that in group A (4.390 3 +/- 0.551 9), showing significant differences (P < 0.05). The mRNA expression of Col II in group C was significantly higher than those in groups A and B (P < 0.05), the mRNA expression of MMP-13 in group C was significantly lower than that in group B (P < 0.05) but there was no significant difference when compared with group A (P > 0.05). The mRNA expression of j-catenin in group C was significantly lower than that in group B (P < 0.05) and higher than that in group A (P < 0.05). CONCLUSION ALN can protect rat chondrocyte from OA induced by IL-1beta in vitro possibly by upregulating Col II and inhibiting the expression of MMP-13 and beta-catenin in the chondrocytes.
AN IMPACT OF INFLATION AND EXCHANGE RATE ON STOCK RETURNS: EVIDENCE FROM INDIA

The study investigates the existence of relationship between Indian stock market and two macro economic variables namely, inflation and exchange rate. It covers a data period from April 2011 to March 2017. Multivariate Regression Model has been employed to investigate the relationship between BSE Sensex returns as dependent variable, and macro economic variables namely inflation (CPI) and exchange rate (USD- INR) as independent variables. Multicollinearity between independent variables has been tested by calculating Variance Inflation Factor and Tolerance statistics. Both the tests paved the way for application of multivariate regression as multicollinearity among independent variables is not found. The Results of multivariate regression show evidence of positive significant relationship between inflation and stock returns and insignificant relationship between exchange rate and stock returns in India. The findings suggest that Indian Stock Market is driven by inflation.
Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion

Anaemia is a common condition among patients admitted to hospital medicosurgical departments, as well as in critically ill patients. Anaemia is more frequently due to absolute iron deficiency (e.g. chronic blood loss) or functional iron deficiency (e.g. chronic inflammatory states), with other causes being less frequent. In addition, preoperative anaemia is one of the major predictive factors for perioperative blood transfusion. In surgical patients, postoperative anaemia is mainly caused by perioperative blood loss, and it might be aggravated by inflammation‐induced inhibition of erythropoietin and functional iron deficiency (a condition that cannot be corrected by the administration of oral iron). All these mechanisms may be involved in the anaemia of the critically ill. Intravenous iron administration seems to be safe, as very few severe side‐effects were observed, and may result in hastened recovery from anaemia and lower transfusion requirements. However, it is noteworthy that many of the recommendations given for intravenous iron treatment are not supported by a high level of evidence and this must be borne in mind when making decisions regarding its application to a particular patient. Nonetheless, this also indicates the need for further large, randomized controlled trials on the safety and efficacy of intravenous iron for the treatment of anaemia in different clinical settings.