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Litoria rothii is a widespread pelodryadid frog with a charismatic laughing advertisement call, distributed across the Australian Monsoon Tropics and southern New Guinea. Given its large distribution spanning well-known biogeographic barriers, variation in male advertisement calls and the prevalence of unresolved species complexes in the Australian frog fauna, we examine the genetic, morphological and acoustic diversity in the species from across its range. Our analyses reveal the presence of a previously unrecognised species in western parts of the range of L. rothii sensu lato, which we describe herein as a new species. Litoria ridibunda sp. nov. is distinguished from L. rothii on the basis of paraphyly of nuclear gene trees with L. everetti from Indonesia, colour patterns on the posterior thigh and male advertisement calls. Compared to L. rothii, the new species has a less contrasting pattern on the posterior thigh and a male advertisement call with a greater number of notes per call and a greater call duration. In particular, the magnitude of call differences between the species is highest where the ranges of the two species are in proximity in north-western Queensland. Our study further emphasises the undiagnosed diversity that remains in Australian frogs, even in relatively large, charismatic, frequently encountered species that often share human dwellings.
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Anuros , Humanos , Animais , Austrália , Anuros/genética , Anuros/anatomia & histologia , FilogeniaRESUMO
The bleating tree frog (Litoria dentata) is one of the more prominent pelodryadid frogs of eastern Australia by virtue of its extremely loud, piercing, male advertisement call. A member of the Litoria rubella species group, L. dentata has a broad latitudinal distribution and is widespread from coastal and subcoastal lowlands through to montane areas. A recent mitochondrial DNA analysis showed a deep phylogeographic break between populations of L. dentata on the mid-north coast of New South Wales. Here we extended the mitochondrial survey with more geographically comprehensive sampling and tested the systematic implications of our findings with nuclear genome wide single-nucleotide polymorphism, morphological and male advertisement call datasets. While similar in appearance and in male advertisement call, our integrative analysis demonstrates the presence of three species which replace each other in a north-south series. We redescribe Litoria dentata, which is restricted to coastal north-eastern New South Wales, and formally describe Litoria balatus sp. nov., from south-eastern Queensland, and Litoria quiritatus sp. nov., from the mid-coast of New South Wales to north-eastern Victoria.
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Anuros , Rubéola (Sarampo Alemão) , Animais , Anuros/genética , DNA Mitocondrial/genética , Masculino , FilogeniaRESUMO
Strange matter is believed to exist in the cores of neutron stars based on simple kinematics. If this is true, then hyperon-nucleon interactions will play a significant part in the neutron star equation of state. Yet, compared to other elastic scattering processes, there is very little data on Λ-N scattering. This experiment utilized the CEBAF Large Acceptance Spectrometer (CLAS) detector to study the ΛpâΛp elastic scattering cross section in the incident Λ momentum range 0.9-2.0 GeV/c. These are the first data on this reaction since the 1970s. The new cross sections have significantly better accuracy and precision than the existing world data, and the techniques developed here can also be used in future experiments.
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Long-distance acoustic signals are widely used in animal communication systems and, in many cases, are essential for reproduction. The acoustic adaptation hypothesis (AAH) implies that acoustic signals should be selected for further transmission and better content integrity under the acoustic constraints of the habitat in which they are produced. In this study, we test predictions derived from the AAH in frogs. Specifically, we focus on the difference between torrent frogs and frogs calling in less noisy habitats. Torrents produce sounds that can mask frog vocalizations and constitute a major acoustic constraint on call evolution. We combine data collected in the field, material from scientific collections and the literature for a total of 79 primarily Asian species, of the families Ranidae, Rhacophoridae, Dicroglossidae and Microhylidae. Using phylogenetic comparative methods and including morphological and environmental potential confounding factors, we investigate putatively adaptive call features in torrent frogs. We use broad habitat categories as well as fine-scale habitat measurements and test their correlation with six call characteristics. We find mixed support for the AAH. Spectral features of torrent frog calls are different from those of frogs calling in other habitats and are related to ambient noise levels, as predicted by the AAH. However, temporal call features do not seem to be shaped by the frogs' calling habitats. Our results underline both the complexity of call evolution and the need to consider multiple factors when investigating this issue.
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Adaptação Fisiológica/fisiologia , Anuros/fisiologia , Meio Ambiente , Vocalização Animal/fisiologia , Animais , Anuros/classificação , FilogeniaRESUMO
Essentials Platelets express retinoic acid receptor (RAR)α protein, specifically binding target mRNAs. mRNAs under RARα control include MAP1LC3B2, SLAIN2, and ANGPT1. All-trans retinoic acid (atRA) releases RARα from its target mRNA. RARα expressed in human platelets exerts translational control via direct mRNA binding. SUMMARY: Background Translational control mechanisms in platelets are incompletely defined. Here, we determined whether the nuclear transcription factor RARα controls protein translational events in human platelets. Methods Isolated human platelets were treated with the pan-RAR agonist all-trans-retinoic acid (atRA). Global and targeted translational events were examined. Results Stimulation of platelets with atRA significantly increased global protein expression. RARα protein bound to a subset of platelet mRNAs, as measured by next-generation RNA-sequencing. In-depth analyses of 5' and 3'-untranslated regions of the RARα-bound mRNAs revealed consensus RARα binding sites in microtubule-associated protein 1 light chain 3 beta 2 (MAP1LC3B2), SLAIN motif-containing protein 2 (SLAIN2) and angiopoietin-1 (ANGPT1) transcripts. When platelets were treated with atRA, binding interactions between RARα protein and mRNA for MAP1LC3B2, SLAIN2 and ANGPT1 were significantly decreased. Consistent with the release of bound RARα protein from MAP1LCB2mRNA, we observed an increase in the synthesis of MAP1LC3B2 protein. Conclusions These findings provide the first evidence that RARα, a nuclear transcriptional factor, regulates synthetic events in anucleate human platelets. They also reveal an additional non-genomic role for RARα in platelets that may have implications for the vitamin A-dependent signaling in humans.
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Plaquetas/metabolismo , Proteínas Sanguíneas/biossíntese , Proteínas Sanguíneas/genética , Receptor alfa de Ácido Retinoico/sangue , Angiopoietina-1/biossíntese , Angiopoietina-1/sangue , Angiopoietina-1/genética , Sequência de Bases , Sítios de Ligação/genética , Plaquetas/efeitos dos fármacos , Humanos , Técnicas In Vitro , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas Associadas aos Microtúbulos/sangue , Proteínas Associadas aos Microtúbulos/genética , Biossíntese de Proteínas , RNA Mensageiro/sangue , RNA Mensageiro/genética , Receptor alfa de Ácido Retinoico/genética , Tretinoína/farmacologiaRESUMO
Through assay analysis into an excess of 1M H2SO4 at fixed temperature a technique has been developed for uranium concentration analysis by visible absorption spectroscopy over an assay concentration range of 1.8-13.4mgU/g. Once implemented for a particular spectrophotometer and set of spectroscopic cells this technique promises to provide more rapid results than a classical method such as Davies-Gray (DG) titration analysis. While not as accurate and precise as the DG method, a comparative analysis study reveals that the spectroscopic method can analyze for uranium in well characterized uranyl(VI) solution samples to within 0.3% of the DG results. For unknown uranium solutions in which sample purity is less well defined agreement between the developed spectroscopic method and DG analysis is within 0.5%. The technique can also be used to detect the presence of impurities that impact the colorimetric analysis, as confirmed through the analysis of ruthenium contamination. Finally, extending the technique to other assay solution, 1M HNO3, HCl and Na2CO3, has also been shown to be viable. Of the four aqueous media the carbonate solution yields the largest molar absorptivity value at the most intensely absorbing band, with the least impact of temperature.
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Essentials Co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. We determined pathogenic variants in a three-generational pedigree with excessive bleeding. Bleeding occurred with concurrent variants in prostaglandin synthase-1 (PTGS-1) and factor VIII. The PTGS-1 variant was associated with functional defects in the arachidonic acid pathway. SUMMARY: Background Inherited human variants that concurrently cause disorders of primary hemostasis and coagulation are uncommon. Nevertheless, rare cases of co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. Objective We prospectively sought to determine pathogenic variants in a three-generational pedigree with excessive bleeding. Patients/methods Platelet number, size and light transmission aggregometry to multiple agonists were evaluated in pedigree members. Transmission electron microscopy determined platelet morphology and granule content. Thromboxane release studies and light transmission aggregometry in the presence or absence of prostaglandin G2 assessed specific functional defects in the arachidonic acid pathway. Whole exome sequencing (WES) and targeted nucleotide sequence analysis identified potentially deleterious variants. Results Pedigree members with excessive bleeding had impaired platelet aggregation with arachidonic acid, epinephrine and low-dose ADP, as well as reduced platelet thromboxane B2 release. Impaired platelet aggregation in response to 2MesADP was rescued with prostaglandin G2 , a prostaglandin intermediate downstream of prostaglandin synthase-1 (PTGS-1) that aids in the production of thromboxane. WES identified a non-synonymous variant in the signal peptide of PTGS-1 (rs3842787; c.50C>T; p.Pro17Leu) that completely co-segregated with disease phenotype. A variant in the F8 gene causing hemophilia A (rs28935203; c.5096A>T; p.Y1699F) was also identified. Individuals with both variants had more severe bleeding manifestations than characteristic of mild hemophilia A alone. Conclusion We provide the first report of co-existing variants in both F8 and PTGS-1 genes in a three-generation pedigree. The PTGS-1 variant was associated with specific functional defects in the arachidonic acid pathway and more severe hemorrhage.
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Fator VIII/genética , Hemorragia/genética , Prostaglandina-Endoperóxido Sintases/genética , Adulto , Idoso , Ácido Araquidônico/metabolismo , Criança , Ciclo-Oxigenase 1/genética , Saúde da Família , Feminino , Frequência do Gene , Variação Genética , Hemorragia/sangue , Hemorragia/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Agregação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Prostaglandina-Endoperóxido Sintases/sangue , Tromboxano B2/genética , Adulto JovemRESUMO
Our aim was to develop an automated multiparametric MR imaging analysis of routinely acquired imaging sequences to identify areas of focally recurrent high-grade glioma. Data from 141 patients treated with radiation therapy with a diagnosis of high-grade glioma were reviewed. Strict inclusion/exclusion criteria identified a homogeneous cohort of 12 patients with a nodular recurrence of high-grade glioma that was amenable to focal re-irradiation (cohort 1). T1WI, FLAIR, and DWI data were used to create subtraction maps across time points. Linear regression was performed to identify the pattern of change in these 3 imaging sequences that best correlated with recurrence. The ability of these parameters to guide treatment decisions in individual patients was assessed in a separate cohort of 4 patients who were treated with radiosurgery for recurrent high-grade glioma (cohort 2). A leave-one-out analysis of cohort 1 revealed that automated subtraction maps consistently predicted the radiologist-identified area of recurrence (median area under the receiver operating characteristic curve = 0.91). The regression model was tested in preradiosurgery MRI in cohort 2 and identified 8 recurrent lesions. Six lesions were treated with radiosurgery and were controlled on follow-up imaging, but the remaining 2 lesions were not treated and progressed, consistent with the predictions of the model. Multiparametric subtraction maps can predict areas of nodular progression in patients with previously treated high-grade gliomas. This automated method based on routine imaging sequences is a valuable tool to be prospectively validated in subsequent studies of treatment planning and posttreatment surveillance.
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UNLABELLED: Essentials Platelets employ proteins/signaling pathways traditionally thought reserved for nuclear niche. We determined retinoic-acid-receptor alpha (RARα) expression and function in human platelets. RARα/actin-related protein-2/3 complex (Arp2/3) interact via non-genomic signaling in platelets. RARα regulates Arp2/3-mediated actin cytoskeletal dynamics and platelet spreading. SUMMARY: Background Platelets utilize proteins and pathways classically reserved for the nuclear niche. Methods We determined whether human platelets express retinoic-acid-receptor family members, traditionally thought of as nuclear transcription factors, and deciphered the function of RARα. Results We found that RARα is robustly expressed in human platelets and megakaryocytes and interacts directly with actin-related protein-2/3 complex (Arp2/3) subunit 5 (Arp2/3s5). Arp2/3s5 co-localized with RARα in situ and regulated platelet cytoskeletal processes. The RARα ligand all-trans retinoic acid (atRA) disrupted RARα-Arp2/3 interactions. When isolated human platelets were treated with atRA, rapid cytoskeletal events (e.g. platelet spreading) were inhibited. In addition, when platelets were cultured for 18 h in the presence of atRA, actin-dependent morphological changes (e.g. extended cell body formation) were similarly inhibited. Using in vitro actin branching assays, RARα and Arp2/3-regulated complex actin branch formation was demonstrated. Consistent with inhibition of cytoskeletal processes in platelets, atRA, when added to this branching assay, resulted in dysregulated actin branching. Conclusion Our findings identify a previously unknown mechanism by which RARα regulates Arp2/3-mediated actin cytoskeletal dynamics through a non-genomic signaling pathway. These findings have broad implications in both nucleated and anucleate cells, where actin cytoskeletal events regulate cell morphology, movement and division.
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Actinas/metabolismo , Plaquetas/metabolismo , Citoesqueleto/metabolismo , Receptor alfa de Ácido Retinoico/metabolismo , Proteína 2 Relacionada a Actina/metabolismo , Proteína 3 Relacionada a Actina/metabolismo , Antígenos CD34/metabolismo , Apoptose , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Espectrometria de Massas , Microscopia de Fluorescência , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismoAssuntos
Aberrações Cromossômicas , França , História do Século XX , História do Século XXI , Leucemia/genética , Pediatria , MédicosRESUMO
Optical rectification is demonstrated in (110)-cut ZnGeP(2) (ZGP) providing broadband terahertz (THz) generation. The source is compared to both GaP and GaAs over a wavelength range of 1150 nm to 1600 nm and peak-intensity range of 0.5 GW/cm(2) to 40 GW/cm(2). ZGP peak-to-peak field amplitude is larger than in the other materials due to either lower nonlinear absorption or larger second-order nonlinearity. This material is well suited for broadband THz generation across a wide range of infrared excitation wavelengths.
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A new method of estimating the lower flammability limit (LFL) of general organic compounds is presented. The LFL is predicted at 298 K for gases and the lower temperature limit for solids and liquids from structural contributions and the ideal gas heat of formation of the fuel. The average absolute deviation from more than 500 experimental data points is 10.7%. In a previous study, the widely used modified Burgess-Wheeler law was shown to underestimate the effect of temperature on the lower flammability limit when determined in a large-diameter vessel. An improved version of the modified Burgess-Wheeler law is presented that represents the temperature dependence of LFL data determined in large-diameter vessels more accurately. When the LFL is estimated at increased temperatures using a combination of this model and the proposed structural-contribution method, an average absolute deviation of 3.3% is returned when compared with 65 data points for 17 organic compounds determined in an ASHRAE-style apparatus.
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Incêndios , Compostos Orgânicos/química , TemperaturaRESUMO
We measured maximum temperature rises on the side of the face after 6 min of continuous mobile phone operation using two models of AMPS analog phones operating in the 835 MHz band and three early model GSM digital phones operating in the 900 MHz band. For the GSM phones the highest recorded temperature rise difference was 2.3 degrees C and for the AMPS phones it was 4.5 degrees C, both at locations on the cheek. The higher differential temperature rise between AMPS and GSM may reflect the higher maximum average operating power of AMPS (600 mW) versus GSM900 (250 mW). Additionally, we compared temperature changes at a consistent location on the cheek for an AMPS phone that was inoperative (-0.7 degrees C), transmitting at full power (+2.6 degrees C) and in stand-by mode (+2.0 degrees C). Our results suggest that direct RF heating of the skin only contributes a small part of the temperature rise and that most is due to heat conduction from the handset.
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Telefone Celular , Campos Eletromagnéticos , Temperatura Cutânea/fisiologia , Desenho de Equipamento , Feminino , Humanos , Masculino , Monitorização Fisiológica , Temperatura Cutânea/efeitos da radiaçãoRESUMO
UNLABELLED: A new photocatalytic oxidation air filter (PCO unit) has been designed for aircraft cabin applications. The PCO unit is designed as a regenerable VOC removal system in order to improve the quality of the recirculated air entering the aircraft cabin. The PCO was designed to be a modular unit, with four UV lamps sandwiched between two interchangeable titanium dioxide coated panels. Performances of the PCO unit has been measured in a single pass mode test rig in order to show the ability of the unit to decrease the amount of VOCs (toluene, ethanol, and acetone) entering it (VOCs are fed separately), and in a multipass mode test rig in order to measure the ability of the unit to clean the air of an experimental room polluted with the same VOCs (fed separately). Triangular cell panels have been chosen instead of the wire mesh panels because they have higher efficiency. The efficiency of the PCO unit depends on the type of VOCs that challenges it, toluene being the most difficult one to oxidise. The efficiency of the PCO unit decreases when the air flow rate increases. The multipass mode test results show that the VOCs are oxidized but additional testing time would be necessary in order to show if they can be fully oxidized. The intermediate reaction products are mainly acetaldehyde and formaldehyde whose amount depends on the challenge VOC. The intermediate reaction products are also oxidized and additional testing time would be necessary in order to show if they can be fully oxidized. The development of this new photocatalytic air filter is still going on. PRACTICAL IMPLICATIONS: The VOC/odor removing adsorbers are available for only a small proportion of aircraft currently in service. The photocatalytic oxidation (PCO) technique has appeared to be a promising solution to odors problems met in aircraft. This article reports the test results of a new photocatalytic oxidation air filter (PCO unit) designed for aircraft cabin applications. The overall efficiency of the PCO unit is function of the compound (toluene, ethanol, and acetone) that challenges the unit and toluene appears to be the most difficult compound to oxidize. Test results have shown the influence of the design of the PCO unit, the air flow rate and the type of UV on the efficiency of the PCO unit. The results obtained in this study represent a first attempt on the way to design a filter for VOC removal in cabin aircraft applications. The PCO technique used by the tested prototype unit is able to partially oxidized the challenge VOCs but one has to be aware that some harmful intermediate reaction products (mainly formaldehyde and acetaldehyde) are produced during the oxidation process before being partially oxidized too.
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Aeronaves/instrumentação , Filtração/instrumentação , Ventilação/instrumentação , Poluição do Ar em Ambientes Fechados/prevenção & controle , Catálise , Desenho de Equipamento , Humanos , Oxirredução , Fotoquímica , Raios UltravioletaRESUMO
This investigation was designed to determine if suppression of testosterone alters the ventilatory response to carbon dioxide in the presence of high and low levels of oxygen. Eleven healthy male subjects completed a series of rebreathing trials during wakefulness, before and after treatment with a long-acting gonadotropin-releasing hormone agonist. Five subjects also completed studies during non-rapid eye movement (NREM) sleep. During wakefulness, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (P(ET,CO2)) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr) or high oxygen (140 Torr) gas mixture. During each trial P(ET,CO2) increased while oxygen was maintained at a constant level. The threshold of the ventilatory response to carbon dioxide was considered to be the point at which minute ventilation began to rise in a linear fashion as P(ET,CO2) increased. The slope of the ventilatory response above the threshold was used as a measure of sensitivity to carbon dioxide. During NREM sleep, hypocapnia was induced via nasal mechanical ventilation. Several trials were completed until the cessation of mechanical ventilation resulted in a central apnoea which demarcated the threshold of the ventilatory response to carbon dioxide. In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 +/- 0.77 versus 39.40 +/- 0.83 Torr; P = 0.01) and high (46.32 +/- 0.56 versus 44.78 +/- 0.83 Torr; P = 0.01) oxygen levels. An increase in sensitivity (4.82 +/- 0.61 versus 7.17 +/- 1.20 l min(-1) Torr(-1); P = 0.02) was also observed during rebreathing in the presence of high but not low oxygen levels. The increase in sensitivity was accompanied by an increase in carbon dioxide production. The findings observed during NREM sleep were similar to those observed during wakefulness, since the P(ET,CO2) that demarcated the threshold was decreased after leuprolide treatment (42.1 +/- 0.6 versus 39.6 +/- 0.6 Torr; P = 0.002). Additionally, the decrease in P(ET,CO2) required to induce an apnoea was greater after treatment with leuprolide (2.56 +/- 0.25 versus 4.06 +/- 0.29 Torr; P = 0.004). We conclude that suppression of testosterone decreases the threshold of the ventilatory response to carbon dioxide during both wakefulness and sleep.
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Dióxido de Carbono/farmacologia , Leuprolida/farmacologia , Ventilação Pulmonar/efeitos dos fármacos , Adulto , Análise de Variância , Humanos , Masculino , Ventilação Pulmonar/fisiologia , Sono/efeitos dos fármacos , Sono/fisiologia , Vigília/efeitos dos fármacos , Vigília/fisiologiaAssuntos
Gasometria/instrumentação , Coleta de Amostras Sanguíneas/instrumentação , Ferimentos Penetrantes Produzidos por Agulha , Saúde Ocupacional , Equipamentos de Proteção/normas , Desenho de Equipamento , Falha de Equipamento , Humanos , Corpo Clínico Hospitalar , Ferimentos Penetrantes Produzidos por Agulha/etiologia , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Seringas/efeitos adversos , Seringas/normasRESUMO
The efficacy of current landfill gas and radon mitigation measures for the prevention of ingress of organic vapours was investigated by the study of four houses situated on contaminated land in North West England. The chemical present in the ground of greatest concern for health due to exposure to vapour in the indoor air was hexachlorobutadiene (HCBD) and the concentration of this compound was used to assess the effectiveness of the remedial measures. A two stage remediation was undertaken. For a house with a solid floor the top surface of the floor was sealed and then for the second stage a fan was used to pressurise the soil gas beneath the house. In a house with a suspended timber floor, extra air bricks were installed to increase ventilation of the floor void and then a fan to further increase air exchange in the void. HCBD in air was monitored by both pumped and diffusive sampling methods. Control houses were also monitored that were not subject to remediation. It is concluded that the remedial measures used for radon protection of a suspended floor have the potential to reduce indoor HCBD concentrations by about 80%, at least in downstairs rooms (where initial levels were highest). The two techniques used for properties with solid floors do not appear to be as effective, and no benefit at all was seen without making allowances for changes in concentration that occurred in the control house over the same period. Further work is required to test the efficacy of the techniques over a longer period and under different circumstances of type of contamination and building characteristics.
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Poluentes Atmosféricos/química , Poluição do Ar em Ambientes Fechados/prevenção & controle , Butadienos/química , Fungicidas Industriais/química , Inglaterra , Humanos , VentilaçãoRESUMO
The hypocapnic apneic threshold (AT) is lower in women relative to men. To test the hypothesis that the gender difference in AT was due to testosterone, we determined the AT during non-rapid eye movement sleep in eight healthy, nonsnoring, premenopausal women before and after 10-12 days of transdermal testosterone. Hypocapnia was induced via nasal mechanical ventilation (MV) for 3 min with tidal volumes ranging from 175 to 215% above eupneic tidal volume and respiratory frequency matched to eupneic frequency. Cessation of MV resulted in hypocapnic central apnea or hypopnea depending on the magnitude of hypocapnia. Nadir minute ventilation as a percentage of control (%Ve) was plotted against the change in end-tidal CO(2) (Pet(CO(2))); %Ve was given a value of zero during central apnea. The AT was defined as the Pet(CO(2)) at which the apnea closest to the last hypopnea occurred; hypocapnic ventilatory response (HPVR) was defined as the slope of the linear regression Ve vs. Pet(CO(2)). Both the AT (39.5 +/- 2.9 vs. 42.1 +/- 3.0 Torr; P = 0.002) and HPVR (0.20 +/- 0.05 vs. 0.33 +/- 0.11%Ve/Torr; P = 0.016) increased with testosterone administration. We conclude that testosterone administration increases AT in premenopausal women, suggesting that the increased breathing instability during sleep in men is related to the presence of testosterone.
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Hormônios Esteroides Gonadais/farmacologia , Caracteres Sexuais , Síndromes da Apneia do Sono/fisiopatologia , Fases do Sono/fisiologia , Testosterona/farmacologia , Administração Cutânea , Adulto , Dióxido de Carbono , Limiar Diferencial/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/administração & dosagem , Humanos , Hipocapnia/etiologia , Hipocapnia/fisiopatologia , Pressão Parcial , Respiração , Respiração Artificial , Testosterona/administração & dosagem , Volume de Ventilação PulmonarRESUMO
Nonrandom, recurring chromosomal translocations are critical events in the pathogenesis of leukemia. The recently identified TEL/AML1 (CBFA2/EVT6) fusion gene occurs as a result of the t(12;21)(p13;q22) in approximately 25% of children with diagnosed pre-B-cell acute lymphoblastic leukemia (PBC-ALL). To identify changes in gene expression patterns that occur during PBC-ALL disease progression, we used cDNA microarrays to compare expressed sequences from the AT-1 and AT-2 cell lines. These cell lines, from the same patient, were established from two distinct stages of PBC-ALL disease progression, namely, first and second relapse. Analysis of both cell lines with spectral karyotying (SKY) revealed an insertion of chromosome 8 into chromosome 5 and a previously undetected translocation in AT-2 involving chromosomes 1 and 17. Hybridization of cDNA microarrays identified the TCL1 transcript as being overexpressed in the AT-2 cell line relative to AT-1. Northern blot analysis showed an eightfold increase of the TCL1 transcript in AT-2 over AT-1 cells. Western blot analysis showed that the TCL1 protein was expressed more than 50-fold higher in AT-2 than AT-1 cells. TCL1 expression was correlated with TEL expression by reintroducing TEL into AT-2 cells and demonstrating that those cells expressing TEL at high levels showed a decreased expression of endogenous TCL1.
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Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Regulação Leucêmica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Proteínas Proto-Oncogênicas , Proteínas Repressoras/genética , Fatores de Transcrição/biossíntese , Doença Aguda , Diferenciação Celular , Pré-Escolar , Coloração Cromossômica , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 1/ultraestrutura , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 17/ultraestrutura , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 21/ultraestrutura , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 5/ultraestrutura , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 8/ultraestrutura , Subunidade alfa 2 de Fator de Ligação ao Core , DNA Complementar/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/fisiologia , Progressão da Doença , Teste de Complementação Genética , Humanos , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiologia , Células-Tronco Neoplásicas/patologia , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Proteínas Proto-Oncogênicas c-ets , Proteínas Repressoras/biossíntese , Proteínas Repressoras/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Translocação Genética , Células Tumorais Cultivadas/metabolismo , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Soft tissue reconstruction using tissue-engineered constructs requires the development of materials that are biocompatible and support cell adhesion and growth. The objective of this study was to evaluate the use of macroporous hydrogel fragments that were formed using either unmodified alginate or alginate covalently linked with the fibronectin cell adhesion peptide RGD (alginate-RGD). These materials were injected into the subcutaneous space of adult, domesticated female sheep and harvested for histological comparisons at 1 and 3 months. In addition, the alginate-RGD porous fragments were seeded with autologous sheep preadipocytes isolated from the omentum, and these cell-based constructs were also implanted. The results from this study indicate that both the alginate and alginate-RGD subcutaneous implants supported tissue and vascular ingrowth. Furthermore, at all time points of the experiment, a minimal inflammatory response and capsule formation surrounding the implant were observed. The implanted materials also maintained their sizes over the 3-month study period. In addition, the alginate-RGD fragments supported the adhesion and proliferation of sheep preadipocytes, and adipose tissue was present within the transplant site of these cellular constructs, which was not present within the biomaterial control sites.