Miracle-dz/UniFAR-FTUs huggingface dataset:
Intratumoral, not circulating, endothelial progenitor cells share genetic aberrations with glial tumor cells

Literature data indicate that glioma stem cells may give rise to both tumor cells and endothelial progenitor cells (EPCs). Malignant glioma patients usually have increased levels of circulating (EPCs) and these cells are known to contribute to the glioma neovasculature. In this study we compared the intratumoral and circulating EPCs of glioma patients for a set of common glioma genotypical aberrations (amplification of EGFR; deletion of PTEN and aneusomy of chromosomes 7 and 10). We found that the EPCs present in the tumor tissues, not the circulating EPCs, share genetic aberrations with the tumor cells. EPCs with EGFR amplification were found in 46% and with PTEN deletion in 36% of the cases. EPCs with polysomy 7 and monosomy 10 were detected in 56% and 38% of the cases while centrosomal abnormalities in EPCs were found in 68% of the cases. The presence of genetic aberrations of glioma cells in intratumoral EPCs may point to transdifferentiation of glioma stem cells into EPCs. However, the tissue specific CD133 splice variant of blood EPCs was detected in the glioma tissues but not in control brains, suggestive of a blood origin of at least part of the intratumoral EPCs. The findings highlight the complexity of the cellular constituents of glioma neovascularization which should be taken into account when developing anti‐angiogenic strategies for gliomas. J. Cell. Physiol. 228: 1383–1390, 2013. © 2012 Wiley Periodicals, Inc.
Efficacy of Garcinia mangostana L. (mangosteen rind extract) to reduce acne severity

Background: In vitro studies showed that extract of mangosteen rind (EMR) (Garcinia mangostana L.) containing xanthones has antibacterial effect against Propionibacterium acnes and also anti-inflammatory effect. The aim of this study is to determine the efficacy of EMR in reducing acne vulgaris (AV). Methods: A randomized, double-blind, placebo controlled clinical trial was done on 94 subjects (18-30 years) with mild and moderate AV. The treatment group was given 400 mg EMR 3 times daily orally, for 3 weeks and control group was given placebo capsules. As a standard therapy, all subjects were given a topical cream of 0.025% retinoic acid applied on acne lesions during night time. Efficacy was assessed by counting the acne lesion number as well as proportion of subjects with more than 20% decrease in lesion. The decrease of plasma malondialdehyde (MDA) levels were also measured. Results: After 3 weeks of treatment, acne lesion counts was significantly reduced in both groups [from 934 to 584 lesion (37%) in treatment group, p 0.55). The proportion of subjects whose acne lesion reduced ≥ 20% was 73% (33 of 45 subjects) in treatment group vs 66% (27 of 41 subjects) in control (p > 0.2). The level MDA was reduced from 1.16 to 1.02 nmol/mL in treatment group and from 1.32 become 1.02 nmol/mL in control (p > 0.48). Conclusion: Extract of mangosteen rind given orally for 3 weeks clinically reduced acne severity better than placebo, although statistically was not significant. Antioxidant effect of EMR seem to be unspecific in reducing acne severity. (Med J Indones. 2013;22:167-72. doi: 10.13181/mji.v22i3.586)
Evaluation of Bambara groundnut varieties for off-season production in Zimbabwe

Early planting of bambara groundnuts (Vigna subterranea L. Verdc) in the southern Africa enables farmers to fetch premium prices before the markets are flooded with produce from the main summer growing period. However, adaptation of the crop outside the main growing season has not been studied in Zimbabwe. Therefore, this study evaluated 20 varieties at four planting dates covering contrasting temperatures and daylength, at Harare Research Station, during 2000/2001. Planting date was the main plot factor replicated three times and cultivar the subplot. Standard agronomic practices were followed and adequate moisture supplied through supplementary irrigation. Both the planting dates and variety main effects were significant (P most of the secondary traits. Planting date x genotype interaction (G x E) effects were not significant (P and different photothermal conditions. August and September planting dates resulted in high dry pod yield. Varieties BS599, BS537, V2-17, BS520, and Variety-10, had high relative yield, and were the most promising for off-season planting.
Up-regulation of Cavβ3 Subunit in Primary Sensory Neurons Increases Voltage-activated Ca2+ Channel Activity and Nociceptive Input in Neuropathic Pain*

Background: We determined how nerve injury affects calcium channel β (Cavβ) subunits in neuropathic pain. Results: Nerve injury increases Cavβ3 expression level, and Cavβ3 knockdown reduces increased calcium channel activity in primary sensory neurons and pain hypersensitivity. Conclusion: Cavβ3 subunit up-regulation augments calcium channel activity in neuropathic pain. Significance: Understanding molecular changes in sensory neurons is important for developing new treatments for neuropathic pain. High voltage-activated calcium channels (HVACCs) are essential for synaptic and nociceptive transmission. Although blocking HVACCs can effectively reduce pain, this treatment strategy is associated with intolerable adverse effects. Neuronal HVACCs are typically composed of α1, β (Cavβ), and α2δ subunits. The Cavβ subunit plays a crucial role in the membrane expression and gating properties of the pore-forming α1 subunit. However, little is known about how nerve injury affects the expression and function of Cavβ subunits in primary sensory neurons. In this study, we found that Cavβ3 and Cavβ4 are the most prominent subtypes expressed in the rat dorsal root ganglion (DRG) and dorsal spinal cord. Spinal nerve ligation (SNL) in rats significantly increased mRNA and protein levels of the Cavβ3, but not Cavβ4, subunit in the DRG. SNL also significantly increased HVACC currents in small DRG neurons and monosynaptic excitatory postsynaptic currents of spinal dorsal horn neurons evoked from the dorsal root. Intrathecal injection of Cavβ3-specific siRNA significantly reduced HVACC currents in small DRG neurons and the amplitude of monosynaptic excitatory postsynaptic currents of dorsal horn neurons in SNL rats. Furthermore, intrathecal treatment with Cavβ3-specific siRNA normalized mechanical hyperalgesia and tactile allodynia caused by SNL but had no significant effect on the normal nociceptive threshold. Our findings provide novel evidence that increased expression of the Cavβ3 subunit augments HVACC activity in primary sensory neurons and nociceptive input to dorsal horn neurons in neuropathic pain. Targeting the Cavβ3 subunit at the spinal level represents an effective strategy for treating neuropathic pain.
Invariant U2 RNA sequences bordering the branchpoint recognition region are essential for interaction with yeast SF3a and SF3b subunits

U2 small nuclear RNA (snRNA) contains a sequence (GUAGUA) that pairs with the intron branchpoint during splicing. This sequence is contained within a longer invariant sequence of unknown secondary structure and function that extends between U2 and I and stem IIa. A part of this region has been proposed to pair with U6 in a structure called helix III. We made mutations to test the function of these nucleotides in yeast U2 snRNA. Most single base changes cause no obvious growth defects; however, several single and double mutations are lethal or conditional lethal and cause a block before the first step of splicing. We used U6 compensatory mutations to assess the contribution of helix III and found that if it forms, helix III is dispensable for splicing in Saccharomyces cerevisiae. On the other hand, mutations in known protein components of the splicing apparatus suppress or enhance the phenotypes of mutations within the invariant sequence that connect the branchpoint recognition sequence to stem IIa. Lethal mutations in the region are suppressed by Cus1-54p, a mutant yeast splicing factor homologous to a mammalian SF3b subunit. Synthetic lethal interactions show that this region collaborates with the DEAD-box protein Prp5p and the yeast SF3a subunits Prp9p, Prp11p, and Prp21p. Together, the data show that the highly conserved RNA element downstream of the branchpoint recognition sequence of U2 snRNA in yeast cells functions primarily with the proteins that make up SF3 rather than with U6 snRNA.
Absence of Interhemispheric Transfer of Unilateral Visuomotor Learning in Young Children and Individuals With Agenesis of the Corpus Callosum

This study was undertaken to investigate the role of the corpus callosum in interhemispheric transfer of unilateral visuomotor learning. In the first experiment, the cross-manual performance of 4 callosal agenesis participants was compared to that of 4 age- and IQ-matched controls. In the second experiment, normal children of different ages (6-7 and 11-12 years) and adults were submitted to the same task to assess the impact of callosal maturation on interhemispheric transfer. Participants had to make aiming movements from a starting position toward either a central or a lateral target on the same side as the hand used, while maintaining central fixation. Prior to training, a pretest was performed with the hand contralateral to the hand used during learning. Participants were then submitted to a posttest with the untrained hand. All participants learned the unilateral aiming task in the learning phase, as evidenced by a reduction in spatial errors with an increasing number of practice trials. However, acallosal participants and children aged 6 to 7 years failed to transfer the acquired skill from the trained to the untrained hemisphere. These findings suggest that interhemispheric transfer of visuomotor skills cannot be assumed by other structures in the case of agenesis or morphological immaturity of the corpus callosum. The results further indicate that unilateral visuomotor learning leads to the formation of a single, unihemispheric engram in the absence, whether functional or anatomical, of the corpus callosum.
Various methods of analysis of mdr-1/P-glycoprotein in human colon cancer cell lines.

BACKGROUND Multidrug resistance (MDR) mediated by high levels of mdr-1 (also known as PGY1)/P-glycoprotein (Pgp) has been studied in tissue culture systems; however, most tumor samples which express mdr-1/Pgp have much lower levels. PURPOSE We wanted to determine if levels seen clinically could be detected by commonly used methods and to determine if these levels conferred MDR reversible by Pgp antagonists. METHODS We studied multi-drug-resistant cell lines and sublines with levels of mdr-1/Pgp expression comparable to those seen clinically. We evaluated the expression of mdr-1 RNA by Northern blot analysis, slot blot analysis, polymerase chain reaction (PCR) analysis, and in situ hybridization. We evaluated protein expression by immunofluorescence, immunohistochemistry, fluorescence-activated cell sorting, and immunoblotting analyses. Drug resistance and reversibility were determined by cell growth during continuous drug exposure. RESULTS In most cases, the low level of mdr-1/Pgp present in these cell lines could be detected by each method, but the assays were at the limit of sensitivity for all methods except the PCR method. These low levels of mdr-1/Pgp are capable of conferring MDR, which can be antagonized by verapamil. CONCLUSIONS Levels of mdr-1/Pgp similar to those found in clinical samples can be detected by each of these methods, but the PCR method was the most sensitive and most reliably quantitative. IMPLICATIONS In vitro sensitization by the addition of verapamil in cell lines with these low levels of mdr-1/Pgp suggests that clinically detected levels may confer drug resistance in vivo.
The developmental origins of health and disease: importance for animal production

The importance of management of pregnant animals during pregnancy has been long known to have effects on the quality of their offspring products. In this review, after defining and setting up the current understanding of the Developmental Origins of Health and Disease (DOHaD), effects on traits relevant to animal production, such as meat quality and lactation as well as general health are discussed, with a special interest for effects of periconceptional nutrition.
Influence of low-level exposure to Fusarium mycotoxins on selected immunological and hematological parameters in young swine.

The effects of low dietary concentrations of Fusarium mycotoxins (deoxynivalenol (DON), 15-acetyl-DON, and zearalenone) on growth, immunological, and hematological parameters were determined in young pigs during a 28-day feeding experiment. Clean and naturally contaminated corn were incorporated into basal diets formulated to contain 0.00, 0.75, 1.50, and 3.00 mg DON/kg diet. A pair-fed control animal was used for comparison with each animal receiving the highest level of contamination (diet 4). Skin temperature, measured during the first week of the experiment, decreased linearly as the dietary mycotoxin concentration increased. Several other linear effects were observed: depressed feed intake throughout the experiment, reduction in thyroid size (absolute/relative), and changes in the appearance of the esophageal region of the stomach (thicker and higher degree of folding with increasing toxin concentration). Serum T4 (thyroxine) levels increased quadratically after 7 and 28 days of exposure compared to control animals. This change coincided with an increase in albumin levels, a decrease in alpha-globulin levels, and an overall increase in albumin/globulin ratio as the level of contamination increased. After immunization with sheep red blood cells (SRBC), animals fed contaminated diets showed a delayed response in peak titers. At the end of the experiment an increase in the segmented neutrophil count was observed. The following observations were made for animals consuming diet 4 as compared to the pair-fed controls: lower skin temperature, better feed efficiency, more corrugated stomachs, reduced alpha-globulin levels, and lower antibody titers to SRBC. (ABSTRACT TRUNCATED AT 250 WORDS)
Isolation and characterization of type III group B streptococcal mutants defective in biosynthesis of the type-specific antigen

Four classes of mutants of type III group B streptococcus were isolated by serial subculture of the wild-type strain in the presence of type III-specific rabbit antiserum. Class I mutants no longer synthesized sialic acid but still elaborated the core antigen. Class II mutants maintained the ability to synthesize sialic acid but could not attach it to the core antigen. Class III mutants did not produce the core antigen but still synthesized intracellular sialic acid. Class IV mutants synthesized the complete antigen; however, only approximately 4% of the antigen synthesized was found associated with the cell wall peptidoglycan (in the wild-type strain greater than 85% of the antigen synthesized is covalently attached to the cell wall peptidoglycan), whereas greater than 90% of the antigen was secreted into the growth medium. Production of other components (CAMP factor, group B antigen, beta-hemolysin, neuraminidase) by these mutants appeared similar to those of the wild-type strain. Mouse lethality studies of these strains indicated that all four classes have greater than 3 log10-higher 50% lethal dose values than that of the wild-type strain. To understand the basis for this variation, the invasive ability of the wild-type strain and the sialic acid-deficient mutant strain M-10 (class I) was examined. Mice received 10(5) CFU of each organism; they were then sacrificed at various times postinoculation, and viable group B streptococci from different organs were enumerated. Mice were able to clear M-10 more efficiently, with greater than 80% of M-10 cells being phagocytized by macrophages within 1 h, whereas the wild-type strain was able to evade phagocytic killing and disseminate to other tissues. These data, therefore, strongly indicate that the sialic acid moiety greatly enhances the virulence of the type III antigen. In addition, the level of cell-associated type-specific antigen appears to contribute significantly to the pathogenicity of the organism.
Growth, developmental stability and immune response in juvenile Japanese quails (Coturnix coturnix japonica)

Stresses are environmental factors which restrict growth or cause a potentially adverse change in an organism. The exposure of developing organisms to environmental stresses may have several physiological consequences including a decrease in immunocompetence. However, mounting an immune response against a foreign antigen may in itself constitute a cost for developing organisms. This cost has potentially long–term consequences for adult function and fitness. This study examines the growth and developmental stability of Japanese quail chicks challenged by three non–pathogenic antigens: sheep red blood cells, which assess T–cell–dependent immune responses, and Mycoplasma synoviae and Newcastle disease virus, which assess T–cell–independent responses. Increases in both body mass and wing length were significantly reduced in antigen–challenged compared to control birds. Fluctuating asymmetry (FA) in the masses of primary feathers increased from the innermost (1) to the outermost (10) position on the wing. In addition, antigen challenge by M. synoviae and sheep red blood cells was associated with an increase in FA. The cell–mediated response measured by reaction to phytohaemagglutinin (PHA) was significantly depressed in M. synoviae–challenged birds. White blood cell (WBC) counts, except for monocytes, were elevated in response to all three antigen treatments. Total plasma protein and haematocrit also differed between treatments but exhibited no clear relationship to antigen challenge. Immune responses clearly impose a stress on developing chicks. Additional research will be required to determine the long–term consequences of developmental stress and assess the selective forces that influence the strength of the immune responses of chicks.
Expansion and Contraction of HIV-Specific CD4 T Cells with Short Bursts of Viremia, but Physical Loss of the Majority of These Cells with Sustained Viral Replication1

Chronic infection with the HIV results in poor HIV-specific CD4 T cell proliferation, but more recent analyses using intracellular cytokine staining demonstrated that IFN-γ-producing, HIV-specific CD4 T cells can be detected for years in HIV-infected subjects. Because it is not known whether the majority of HIV-specific T cells are lost or become dysfunctional, we examined the kinetics of the T cell response over an extended period of time using a panel of 10 HLA-DR tetramers loaded with HIV p24 peptides. Tetramer+ CD4 T cells were present at a relatively high frequency during acute infection, but the size of these populations substantially contracted following suppression of viral replication. Short-term cessation of antiretroviral therapy resulted in a burst of viral replication and concomitant expansion of tetramer+ CD4 T cells, and these populations again contracted following reinitiation of therapy. The kinetics with which these cell populations contracted were characteristic of effector T cells, a conclusion that was supported by their phenotypic (CCR7−CD45RA−) and functional properties (IFN-γ+). Continued high-level viremia resulted in the physical loss of the majority of tetramer+ CD4 T cells, and the decline of HIV p24-specific CD4 T cells occurred more rapidly and was more substantial than the reduction of total CD4 T cell numbers. We conclude that the population of HIV p24-specific CD4 T cells is initially responsive to changes in the levels of viral Ags, but that the majority of these cells are lost in a setting of chronic viremia.
Changes in pulmonary artery pressure during the acute phase of respiratory distress syndrome treated with three different types of surfactant

We studied the changes in acceleration time/right ventricular ejection time ratio (AT/RVET; indicative of changes in pulmonary artery pressure) calculated from Doppler ultrasound examinations performed before and 1, 6, and 12 h after the first and second doses of surfactant following the administration of each of three different surfactants during the acute phase of the respiratory distress syndrome. Maximum fractional inspired oxygen concentration (FI,O2) and peak inspiratory pressure (PIP) were recorded during each 4 h period from birth for the first 24 h and subsequently every 24 h until 72 h. Eighty‐three infants were studied. Fifty patients weighing >1 kg received Exosurf® (n = 29) or ALEC® (n = 21) and 33 weighing ≤1 kg received Exosurf® (n = 22) or Survanta® (n = 11).
Reverse Gyrase Recruitment to DNA after UV Light Irradiation in Sulfolobus solfataricus*

Induction of DNA damage triggers a complex biological response concerning not only repair systems but also virtually every cell function. DNA topoisomerases regulate the level of DNA supercoiling in all DNA transactions. Reverse gyrase is a peculiar DNA topoisomerase, specific to hyperthermophilic microorganisms, which contains a helicase and a topoisomerase IA domain that has the unique ability to introduce positive supercoiling into DNA molecules. We show here that reverse gyrase of the archaean Sulfolobus solfataricus is mobilized to DNA in vivo after UV irradiation. The enzyme, either purified or in cell extracts, forms stable covalent complexes with UV-damaged DNA in vitro. We also show that the reverse gyrase translocation to DNA in vivo and the stabilization of covalent complexes in vitro are specific effects of UV light irradiation and do not occur with the intercalating agent actinomycin D. Our results suggest that reverse gyrase might participate, directly or indirectly, in the cell response to UV light-induced DNA damage. This is the first direct evidence of the recruitment of a topoisomerase IA enzyme to DNA after the induction of DNA damage. The interaction between helicase and topoisomerase activities has been previously proposed to facilitate aspects of DNA replication or recombination in both Bacteria and Eukarya. Our results suggest a general role of the association of such activities in maintaining genome integrity and a mutual effect of DNA topology and repair.
VEGF Secretion by Neuroendocrine Tumor Cells Is Inhibited by Octreotide and by Inhibitors of the PI3K/AKT/mTOR Pathway

Gastroenteropancreatic (GEP) endocrine tumors are hypervascular tumors able to synthesize and secrete high amounts of VEGF. We aimed to study the regulation of VEGF production in GEP endocrine tumors and to test whether some of the drugs currently used in their treatment, such as so- matostatin analogues and mTOR inhibitors, may interfere with VEGF secretion. We therefore analyzed the effects of the somatostatin analogue octreotide, the mTOR inhibitor rapamycin, the PI3K inhibitor LY294002, the MEK1 inhibitor PD98059 and the p38 inhibitor SB203850 on VEGF secretion, assessed by ELISA and Western blotting, in three murine endocrine cell lines, STC-1, INS-r3 and INS-r9. Octreotide and rapamycin induced a significant decrease in VEGF production by all three cell lines; LY294002 significantly inhibited VEGF production by STC-1 and INS-r3 only. We detected no effect of PD98059 whereas SB203850 significantly inhibited VEGF secretion in INS-r3 and INS-r9 cells only. By Western blotting analysis, we observed decreased intracellular levels of VEGF and HIF-1α under octreotide, rapamycin and LY294002. For rapamycin and LY294002, this effect was likely mediated by the inhibition of the mTOR/HIF-1/VEGF pathway. In addition to its well-known anti-secretory effects, octreotide may also act through the inhibition of the PI3K/Akt pathway, as suggested by the decrease in Akt phosphorylation detected in all three cell lines. In conclusion, our study points out to the complex regulation of VEGF synthesis and secretion in neoplastic GEP endocrine cells and suggests that the inhibition of VEGF production by octreotide and rapamycin may contribute to their therapeutic effects.