Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Radiofrequencies on the Immune System : from in Utero through Childhood to Adult life exposure

The immune system normally carries out protective responses against pathogens. Perturbing agents such as toxic compounds and ionizing radiation, as well as some pathogens, can compromise the integrity of the immune system. Alterations in immune functions may results in ineffective responses against pathogens, reduction in tumor surveillance, and development of immune-mediated-diseases. In the last decades, the effects on the immune system of a large body of chemical compounds and physical agents has been investigated. More recently, great attention was dedicated to the effects of exposure to noxious agents during early life. Perinatal life is, indeed, a critic stage in the development of the vertebrate immune system. Exposure to toxic compounds, at levels producing limited transient effects in adults, results in long-lasting or even permanent immune deficits when it occurs during perinatal life. The possible effects of exposure to RF radiation have been investigated in several biological systems, including the immune system. A large number of studies were conducted on lymphoid cells using rodents, rodent and human cell lines, or human peripheral blood lymphocytes to investigate the potential harmful of RF electromagnetic field exposure. In our laboratory we studied the effects of the exposure to GSM-modulated 900 MHz RF and WiFi (2.45 GHz) EMF on the immune system in adult animals, newborns and embryos. An overview of our results is described in the present work.
eEF1A Isoforms Change in Abundance and Actin-Binding Activity during Maize Endosperm Development1

Eukaryotic elongation factor 1A (eEF1A) appears to be a multifunctional protein because several biochemical activities have been described for this protein, in addition to its role in protein synthesis. In maize (Zea mays) endosperm, the synthesis of eEF1A is increased in o2 (opaque2) mutants, and its concentration is highly correlated with the protein-bound lysine content. To understand the basis of this relationship, we purified eEF1A isoforms from developing endosperm and investigated their accumulation and their functional and structural properties. Formation of three isoforms appears to be developmentally regulated and independent of the o2 mutation, although one isoform predominated in one high lysine o2 inbred. The purified proteins differ in their ability to bind F-actin in vitro, suggesting that they are functionally distinct. However, they share similar aminoacyl-tRNA-binding activities. Tandem mass spectrometry revealed that each isoform is composed of the four same gene products, which are modified posttranslationally by methylation and phosphorylation. The chemical differences that account for their different actin-binding activities could not be determined.
Multisite management study of menorrhagia with abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral tranexamic acid

The optimal management of menorrhagia among women with abnormal laboratory haemostasis is uncertain. In a crossover study, 116 women with menorrhagia [pictorial blood assessment chart (PBAC) score >100], negative gynaecological evaluation and abnormal laboratory haemostasis were randomly assigned to either intranasal desmopressin (IN‐DDAVP) or tranexamic acid (TA) therapy for two menstrual cycles. The subjects then crossed over to the second study drug for two additional cycles. Menstrual blood loss (MBL) was measured by PBAC scores at baseline and after each menstrual cycle. Quality of life (QOL) was assessed with four validated instruments. There was a statistically significant decrease in PBAC scores for both treatments. On average, the estimated decrease in the PBAC from baseline was −64·1 [95% confidence interval (CI) = −88·0, −40·3] for IN‐DDAVP and −105·7 (95% CI = −130·5, −81·0) for TA. The decrease in PBAC score was greater for TA than IN‐DDAVP (a difference of 41·6, P‐value = 0·0002, 95% CI = 19·6, 63·6). The test for treatment‐type effect was significant (P < 0·0001) suggesting a greater reduction in PBAC score with TA. Use of both IN‐DDAVP and TA improved QOL by all four instruments. We conclude that both medications reduced MBL and improved QOL among females with menorrhagia and abnormal laboratory haemostasis, but TA proved more effective.
Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro

Telomerase activity is detected in more than 90% of examined tumors but not in most normal somatic cells. Among three subunits of human telomerase, human telomerase reverse transcriptase (hTERT) is the rate-limiting component for telomerase activity. Therefore, targeting hTERT represents a promising approach for diminishing telomerase function that will probably not cause substantial side effects on telomerase negative somatic cells. To explore the effects of antisense hTERT (ahTERT) on the malignant phenotypes of human SGC-7901 gastric cancer cell line in vitro, an antisense eukaryotic expression vector of hTERT was constructed by gene recombinant technology. Telomerase activity by telomeric repeat amplification protocol–ELISA, mRNA of telomerase subunits, c-myc and bcl-2 by reverse transcript-PCR, terminal restriction fragment (TRF) by Southern blot, cell cycle distribution by flow cytometry and protein expression of hTERT, c-myc and bcl-2 by Western blot were analyzed in SGC-7901 cells before and after transfection. Cloning efficiency assay in soft agar and tumorigenesis in nude mice were also examined and evaluated in the above cells. The results demonstrated that after ahTERT transfection, the proliferation of SGC-7901 cells was significantly inhibited. Further study showed that telomerase activity, telomere length, the mRNA and protein expression of hTERT, bcl-2 and c-myc were decreased in ahTERT-transfected cells. There were, however, no obvious effects on transcription of human telomerase RNA (hTR) and human telomerase associated protein1 (TP1) in both transfected and untransfected cells. Flow cytometric analysis displayed an accumulation of G0/G1 phase and a decreasing proliferation index (PI) in ahTERT-transfected cells. Moreover, no tumorigenicity was found after subcutaneous injection of ahTERT-transfected cells in nude mice, whereas palpable tumors were observed in mice injected with control cells. Our study indicates that exogenous ahTERT can inhibit proliferation and partially reverse malignant phenotypes of SGC-7901 cells via the suppression of telomerase activity, hTERT, c-myc and bcl-2 expression. Antisense technology targeted hTERT strategy might be a potential approach for gastric cancer therapy.
Delineation of the Hydroxyapatite-nucleating Domains of Bone Sialoprotein*

Bone sialoprotein (BSP) is a highly modified, anionic phosphoprotein that is expressed almost exclusively in mineralizing connective tissues and has been shown to be a potent nucleator of hydroxyapatite (HA). Two polyglutamic acid (poly[E]) regions, predicted to be in an α-helical conformation and located in the amino-terminal half of the molecule, are believed to be responsible for this activity. Using a prokaryotic expression system, full-length rat BSP was expressed and tested for HA nucleating activity in a steady-state agarose gel system. The unmodified protein is less potent than native bone BSP, indicating a role for the post-translational modifications in HA nucleation. Site-directed mutagenesis of the poly[E] regions in full-length BSP was performed, replacing the poly[E] with either polyaspartic acid (poly[D]) or polyalanine (poly[A]) to examine role of charge and conformation, respectively, in HA nucleation. Replacement of single domains with either poly[A] or poly[D] did not alter nucleating activity nor did replacement of both domains with poly[D]. Replacement of both domains with poly[A], however, significantly decreased nucleating activity. In addition, two recombinant peptides, each encompassing one of the two poly[E] domains, were expressed and tested for nucleating activity. Whereas the peptide encompassing the second poly[E] domain was capable of nucleating HA, the first domain peptide showed no activity. The conformation of the wild-type and mutated proteins and peptides were studied by circular dichroism and small angle x-ray scattering, and no secondary structure was evident. These results demonstrate that a sequence of at least eight contiguous glutamic acid residues is required for the nucleation of HA by BSP and that this nucleating “site” is not α-helical in conformation.
Associations between bone mineral density and vertebral height ratios in women without fracture Pearson ' s correlation Partial correlation coefficient coefficienff

Because no gold standard for the definition of vertebral fracture exists, there has been controversy about whether mild vertebral deformities are truly fractures or simply normal variation in vertebral size and shape. The aim of this study was to assess the associations of mild variations of vertebral height ratios to definite vertebral fractures. In 479 Japanese women (age 53.9 + 9.1 years) who visited our institute for a medical checkup, we performed lateral lumbar radiographs and morphometric parameters were derived by measuring the anterior (Ha), middle (Hm) and posterior (Hp) height of each vertebral body from T12 to L4. Vertebral height ratios, Ha/Hp, Hm/Hp or Hp/Hp' of adjacent vertebrae that were more than 3 SD different from vertebra-specific means of normative data were considered to indicate fractures. Forty-five women were diagnosed with at least one fracture. After excluding the subjects with vertebral fracture, we examined the associations of the variations in vertebral height ratios with age, anthropometric parameters and lumbar bone mineral density (BMD) measured by dualenergy X-ray absorptiometry. Vertebral height ratios, especially Hm/Hp in postmenopausal women, tended to decrease with age and were positively associated with BMD. No significant correlation was observed between anthropometric parameters and vertebral height ratios. Age-related decrease in vertebral height ratios (Ha/Hp and Hm/Hp, each averaged from T12 to L4) was significant even after the correction for BMD. Mean values of height ratios of non-fractured vertebrae adjusted for age and BMD were significantly lower in Correspondence and offprint requests to: Teruki Sone, MD, Department of Nuclear Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-01, Japan. Tel: +81(86)-462-1111. Fax: +81(86)-462-1199. postmenopausal women with vertebral fracture than in those without vertebral fracture. Logistic regression analysis showed that BMD and height ratios of nonfractured vertebrae were independent predictors of vertebral fracture risk. The results suggest that older women, and women with at least one obvious (3 SD) fracture, tend to have mild deformities which do not qualify using the 3 SD definition. These mild deformities may represent real consequences of osteoporosis, because they are more pronounced among women with obvious fracture.
Chronic Kidney Disease—A Common and Serious Complication After Intestinal Transplantation

Background. Chronic kidney disease after organ transplantation is a serious complication that negatively impacts on long-term patient survival. We describe long-term renal function after intestinal transplantation by serial measurements of glomerular filtration rates (GFR) with 51Chromium EDTA clearance. Materials and Methods. Ten patients with at least 6 months survival form the basis of this report. Glomerular filtration rate measurements were performed at baseline, 3 months posttransplantation, and yearly thereafter. Median follow-up time for the cohort was 1.5 years (0.5–7.8 years). Tacrolimus (Prograf) was discontinued in four patients because of impaired renal function. These four patients were switched to sirolimus (Rapamune) at 11, 18, 24, and 40 months posttransplantation. Results. Median baseline GFR was 67 (22–114) mL/min/1.73 m2. In the adult patients, GFR 3 months posttransplantation had decreased to 50% of the baseline. At 1 year, median GFR in the adult patients was reduced by 72% (n=5). Two patients developed renal failure within the first year and required hemodialysis. One of the pediatric patients fully recovered her renal function, the second pediatric patient lost 20% of her baseline GFR at 6 months posttransplantation. Glomerular filtration rate calculated with the modified diet in renal disease formula consistently overestimated GFR by approximately 30% compared with measured GFR. Conclusion. Chronic kidney disease and renal failure are common after intestinal transplantation. These two factors significantly contribute to poor long-term survival rates. Measurements of GFR may help to identify those individuals at risk for developing chronic kidney disease to implement renal sparing strategies.
Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors

Significance Ionotropic glutamate receptors are critical for excitatory transmission and plasticity in the brain and have been implicated in several neurological diseases. The GluA4 subunit of the AMPA-type glutamate receptors is expressed transiently in hippocampal CA1 principal neurons when synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling mechanisms of synaptic plasticity and can fully explain the switch in the kinase dependency of long-term potentiation from PKA to Ca2+/calmodulin-dependent protein kinase II during synapse maturation. GluA4 expression at developing synapses confers a minimal mechanism for activity-dependent AMPA-receptor regulation to facilitate silent synapse activation during early development of glutamatergic synapses. The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling requirements of long-term potentiation (LTP) and can fully explain the switch in the LTP kinase dependency from PKA to Ca2+/calmodulin-dependent protein kinase II during synapse maturation. At immature synapses, activation of PKA leads to a robust potentiation of AMPA-receptor function via the mobilization of GluA4. Analysis of GluA4-deficient mice indicates that this mechanism is critical for neonatal PKA-dependent LTP. Furthermore, lentiviral expression of GluA4 in CA1 neurons conferred a PKA-dependent synaptic potentiation and LTP regardless of the developmental stage. Thus, GluA4 defines the signaling requirements for LTP and silent synapse activation during a critical period of synapse development.
Integrated information visualization to support decision making for use of antibiotics in intensive care: design and usability evaluation

Overuse of antibiotics is a critical problem in intensive care today. The situation is further complicated by the extremely data-intensive environment with clinical data presented in distributed, often stand-alone information systems. To access and interpret all data is a complex and time-consuming technical and cognitive challenge. We propose a holistic integrated visualization in the form of a patient overview to support physicians in decision making for use of antibiotics at intensive care units. Special emphasis is put on analysis of work processes to identify information needs, the development of a visualization tool based on an integrated data model, and usability testing of the tool in combination with an eye-tracking technology. The visualization tool was highly rated in terms of user performance and preferences, and the analysis of users’ visual patterns showed that different types of data visualization may benefit specialist and resident intensive care physicians depending on the task to be performed. A highly interactive tool for integrated information visualization could potentially increase the understanding of a patient's infection status and ultimately enhance decision making for the use of antibiotics.
O NÚCLEO DE INOVAÇÃO TECNOLÓGICA DA UFPE: INSTRUMENTO DE POLÍTICA DE INOVAÇÃO OU OBRIGAÇÃO LEGAL? THE CENTER FOR TECHNOLOGICAL INNOVATION AT UFPR: AN INSTRUMENT OF INNOVATION POLICY OR A LEGAL OBLIGATION?

A partir da definicao do marco legal da inovacao no Brasil em 2004, as Instituicoes Cientificas e Tecnologicas (ICTs) foram obrigadas a criar os Nucleos de Inovacao Tecnologica (NITs) para gerenciar sua politica de inovacao institucional. Embora algumas universidades do pais ja contassem com interfaces para gerenciar a propriedade intelectual (PI) e a transferencia de tecnologia (TT), o processo de institucionalizacao dos NITs so ocorreu apos a obrigatoriedade imposta pela Lei de Inovacao. A questao e, portando, compreender se NITs tem cumprido plenamente os propositos para os quais foram criados. Este trabalho tem como objetivo analisar como o NIT da Universidade Federal de Pernambuco (UFPE) gerencia a PI e a TT. Para isso, foi realizada uma pesquisa qualitativa cuja tecnica adotada foi o estudo de caso. Os dados foram obtidos por meio de entrevistas semiestruturadas presenciais em profundidade com gestores e professores da UFPE. Os resultados do trabalho apontam que o NIT da UFPE tem um perfil classificado por Lotufo (2009) como administrativo, atuando apenas como uma interface para processar encaminhamentos relativos a PI e executar acoes de cunho exclusivamente operacional. Diferente de outros NITs brasileiros identificados na literatura, o NIT da UFPE ainda nao conseguiu superar fragilidades basicas de modo a permiti-lo atuar efetivamente como um instrumento de politica de inovacao.
Structure, evolution, and comparative genomics of tetraploid cotton based on a high-density genetic linkage map

A high-density linkage map was constructed using 1,885 newly obtained loci and 3,747 previously published loci, which included 5,152 loci with 4696.03 cM in total length and 0.91 cM in mean distance. Homology analysis in the cotton genome further confirmed the 13 expected homologous chromosome pairs and revealed an obvious inversion on Chr10 or Chr20 and repeated inversions on Chr07 or Chr16. In addition, two reciprocal translocations between Chr02 and Chr03 and between Chr04 and Chr05 were confirmed. Comparative genomics between the tetraploid cotton and the diploid cottons showed that no major structural changes exist between DT and D chromosomes but rather between AT and A chromosomes. Blast analysis between the tetraploid cotton genome and the mixed genome of two diploid cottons showed that most AD chromosomes, regardless of whether it is from the AT or DT genome, preferentially matched with the corresponding homologous chromosome in the diploid A genome, and then the corresponding homologous chromosome in the diploid D genome, indicating that the diploid D genome underwent converted evolution by the diploid A genome to form the DT genome during polyploidization. In addition, the results reflected that a series of chromosomal translocations occurred among Chr01/Chr15, Chr02/Chr14, Chr03/Chr17, Chr04/Chr22, and Chr05/Chr19.
Combination treatment with recombinant methioninase enables temozolomide to arrest a BRAF V600E melanoma in a patient-derived orthotopic xenograft (PDOX) mouse model

An excessive requirement for methionine termed methionine dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by methionine deprivation such as with recombinant methioninase (rMETase). The present study used a previously-established patient-derived orthotopic xenograft (PDOX) nude mouse model of BRAF V600E-mutant melanoma to determine the efficacy of rMETase in combination with a first-line melanoma drug, temozolomide (TEM). In the present study 40 melanoma PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n=10); TEM (25 mg/kg, oral 14 consecutive days, n=10); rMETase (100 units, intraperitoneal 14 consecutive days, n=10); combination TEM + rMETase (TEM: 25 mg/kg, oral rMETase: 100 units, intraperitoneal 14 consecutive days, n=10). All treatments inhibited tumor growth compared to untreated control (TEM: p=0.0081, rMETase: p=0.0037, TEM-rMETase: p=0.0024) on day 14 after initiation. However, the combination therapy of TEM and rMETase was significantly more efficacious than either mono-therapy (TEM: p=0.0051, rMETase: p=0.0051). The present study is the first demonstrating the efficacy of rMETase combination therapy in a PDOX model, suggesting potential clinical development, especially in recalcitrant cancers such as melanoma, where rMETase may enhance first-line therapy.
Cross-Sectional and Longitudinal Associations between Household Food Security and Child Anthropometry at Ages 5 and 8 Years in Ethiopia, India, Peru, and Vietnam.

BACKGROUND Poor childhood nutritional status has lifetime effects and food insecurity is associated with dietary practices that can impair nutritional status. OBJECTIVES We assessed concurrent and subsequent associations between food insecurity and height-for-age z scores (HAZs) and body mass index-for-age z scores (BMI-Zs); evaluated associations with transitory and chronic food insecurity; and tested whether dietary diversity mediates associations between food insecurity and nutritional status. METHODS We used data from the Young Lives younger cohort composed of children in Ethiopia (n = 1757), India (n = 1825), Peru (n = 1844), and Vietnam (n = 1828) recruited in 2002 (round 1) at ∼1 y old, with subsequent data collection at 5 y in 2006 (round 2) and 8 y in 2009 (round 3). RESULTS Children from food-insecure households had significantly lower HAZs in all countries at 5 y (Ethiopia, -0.33; India, -0.53; Peru, -0.31; and Vietnam, -0.68 HAZ; all P < 0.001), although results were attenuated after controlling for potential confounders (Ethiopia, -0.21; India, -0.32; Peru, -0.14; and Vietnam, -0.27 HAZ; P < 0.01). Age 5 y food insecurity predicted the age 8 y HAZ, but did not add predictive power beyond HAZ at age 5 y in Ethiopia, India, or Peru. Age 5 y food insecurity predicted the age 8 y BMI-Z even after controlling for the 5 y BMI-Z, although associations were not significant after the inclusion of additional confounding variables (Ethiopia, P = 0.12; India, P = 0.29; Peru, P = 0.16; and Vietnam, P = 0.51). Chronically food-insecure households had significantly lower HAZs than households that were consistently food-secure, although BMI-Zs did not differ by chronic food-insecurity status. Dietary diversity mediated 18.8-30.5% of the association between food security and anthropometry in Vietnam, but mediated to a lesser degree (8.4-19.3%) in other countries. CONCLUSIONS In 4 countries, food insecurity at 5 y of age was associated with both HAZ and BMI-Z at age 8 y, although the association was attenuated after adjusting for other household factors and anthropometry at age 5 y, and remained significant only for the HAZ in Vietnam.