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1.
BMJ Mil Health ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38754974

RESUMO

INTRODUCTION: The US military has frequently used a 'walking blood bank', formally known as an 'emergency donor panel' (EDP) to obtain warm fresh whole blood (WFWB) which is then immediately transfused into the casualty. We describe the frequency of EDP activation by the US military. METHODS: We analysed data from 2007 to 2015 within the Department of Defense Trauma Registry for US, Coalition and US contractor casualties that received at least 1 unit of blood product within the first 24 hours and described the frequency of WFWB use. RESULTS: There were 3474 casualties that met inclusion, of which, 290 casualties (8%) required activation of the EDP. The highest proportion of EDP events was in 2014, whereas the highest number of EDP events was in 2011. Median injury severity scores were higher in the recipients, compared with non-EDP recipients (29 vs 20), as were proportions with serious injuries to the abdomen (43% vs 19%) and extremities (77% vs 65%). The median number of units of all blood products, except for packed red blood cells, was higher for WFWB recipients. Of the WFWB recipients, the median was 5 units (IQR 2-10) with a maximum documented 144 units. There were four documented cases of EDP recipients receiving >100 units of WFWB with only one surviving to hospital discharge. During the study period, there were a total of 3102 (3%) units of WFWB transfused among a total of 104 288 total units. CONCLUSIONS: We found nearly 1 in 11 casualties who received blood required activation of the EDP. Blood from the EDP accounted for 3% of all units transfused. These findings will enable future mission planning and medical training, especially for units with smaller, limited blood supplies. The lessons learned here can also enable mass casualty planning in civilian settings.

2.
Oncogene ; 34(34): 4545, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25619837

RESUMO

Correction to: Oncogene (2015) 34, 4448­4459; doi:10.1038/onc.2014.372; published online 24 November 2014. In this article, published online 24 November 2014, the authors have noticed that the latest supplementary information was not used. The corrected supplementary information (Supplementary Materials) appears online together with this corrigendum. The authors would like to apologise for any inconvenience this may cause

3.
Oncogene ; 34(34): 4448-59, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-25417704

RESUMO

Acquired drug resistance constitutes a major challenge for effective cancer therapies with melanoma being no exception. The dynamics leading to permanent resistance are poorly understood but are important to design better treatments. Here we show that drug exposure, hypoxia or nutrient starvation leads to an early innate cell response in melanoma cells resulting in multidrug resistance, termed induced drug-tolerant cells (IDTCs). Transition into the IDTC state seems to be an inherent stress reaction for survival toward unfavorable environmental conditions or drug exposure. The response comprises chromatin remodeling, activation of signaling cascades and markers implicated in cancer stemness with higher angiogenic potential and tumorigenicity. These changes are characterized by a common increase in CD271 expression concomitantly with loss of differentiation markers such as melan-A and tyrosinase, enhanced aldehyde dehydrogenase (ALDH) activity and upregulation of histone demethylases. Accordingly, IDTCs show a loss of H3K4me3, H3K27me3 and gain of H3K9me3 suggesting activation and repression of differential genes. Drug holidays at the IDTC state allow for reversion into parental cells re-sensitizing them to the drug they were primarily exposed to. However, upon continuous drug exposure IDTCs eventually transform into permanent and irreversible drug-resistant cells. Knockdown of CD271 or KDM5B decreases transition into the IDTC state substantially but does not prevent it. Targeting IDTCs would be crucial for sustainable disease management and prevention of acquired drug resistance.


Assuntos
Melanoma/tratamento farmacológico , Estresse Fisiológico , Animais , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Histona Desmetilases com o Domínio Jumonji/fisiologia , Camundongos , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/fisiologia , Proteínas Nucleares/fisiologia , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Receptores de Fator de Crescimento Neural/análise , Receptores de Fator de Crescimento Neural/fisiologia , Proteínas Repressoras/fisiologia , Transdução de Sinais
4.
Cell Death Differ ; 22(4): 597-611, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25301065

RESUMO

Dual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied systematically. In addition to redox reactivity, heme may adversely alter cellular functions by binding to essential proteins and impairing their function. We studied inducible heme oxygenase (Hmox1)-deficient mouse embryo fibroblast cell lines as a model to systematically explore adaptive and disruptive responses that were triggered by intracellular heme levels exceeding the homeostatic range. We extensively characterized the proteome phenotype of the cellular heme stress responses by quantitative mass spectrometry of stable isotope-labeled cells that covered more than 2000 individual proteins. The most significant signals specific to heme toxicity were consistent with oxidative stress and impaired protein degradation by the proteasome. This ultimately led to an activation of the response to unfolded proteins. These observations were explained mechanistically by demonstrating binding of heme to the proteasome that was linked to impaired proteasome function. Oxidative heme reactions and proteasome inhibition could be differentiated as synergistic activities of the porphyrin. Based on the present data a novel model of cellular heme toxicity is proposed, whereby proteasome inhibition by heme sustains a cycle of oxidative stress, protein modification, accumulation of damaged proteins and cell death.


Assuntos
Heme/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Bortezomib/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Células HEK293 , Proteínas de Choque Térmico/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Complexo de Endopeptidases do Proteassoma/química , Inibidores de Proteassoma/farmacologia , Ligação Proteica , Proteína Sequestossoma-1 , Espectrofotometria Ultravioleta , Ubiquitina/metabolismo
5.
Domest Anim Endocrinol ; 45(3): 122-5, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23932580

RESUMO

Relatively little is known about the physiological roles of microRNAs (miRNAs) during follicular development. Previous evidence from in vitro studies suggests specific roles for a subset of miRNAs, including miR-21, miR-23a, miR-145, miR-503, miR-224, miR-383, miR-378, miR-132, and miR-212, in regulating ovarian follicle development. The objective of this study was to gain insight on the involvement of these miRNAs during follicle maturation. Follicular fluid was aspirated from dominant follicles (>32 mm) during the ovulatory season (July to October) and the anovulatory season (January to March) in each of 5 mares, and the levels of steroids, IGF1, and miRNAs were analyzed by immunoassays and quantitative PCR. Levels of progesterone, testosterone, and IGF1 were lower (P ≤ 0.05) in anovulatory than in ovulatory follicles. Relative to ovulatory follicles, anovulatory follicles had higher (P < 0.05) mean levels of miR-21, miR-23b, miR-378, and miR-202 and tended to have higher (P = 0.06) levels of miR-145. Levels of miR-224 and miR-383 could not be detected in follicular fluid. These novel results indicate a physiological association between increases in follicular miRNA levels and seasonal anovulation in mares; further studies should elucidate the precise involvement of miR-21, miR-23b, miR-145, miR-378, and miR-202 in follicle maturation in the mare.


Assuntos
Cavalos/fisiologia , MicroRNAs/análise , Folículo Ovariano/metabolismo , Ovulação/fisiologia , Animais , Feminino , Líquido Folicular/química , Imunoensaio , Fator de Crescimento Insulin-Like I/análise , MicroRNAs/fisiologia , Folículo Ovariano/química , Folículo Ovariano/fisiologia , Progesterona/análise , Estações do Ano , Testosterona/análise
6.
Reproduction ; 146(3): 273-82, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23813447

RESUMO

Previous evidence from in vitro studies suggests specific roles for a subset of miRNAs, including miR-21, miR-23a, miR-145, miR-503, miR-224, miR-383, miR-378, miR-132, and miR-212, in regulating ovarian follicle development. The objective of this study was to determine changes in the levels of these miRNAs in relation to follicle selection, maturation, and ovulation in the monovular equine ovary. In Experiment 1, follicular fluid was aspirated during ovulatory cycles from the dominant (DO) and largest subordinate (S) follicles of an ovulatory wave and the dominant (DA) follicle of a mid-cycle anovulatory wave (n=6 mares). Follicular fluid levels of progesterone and estradiol were lower (P<0.01) in S follicles than in DO follicles, whereas mean levels of IGF1 were lower (P<0.01) in S and DA follicles than in DO follicles. Relative to DO and DA follicles, S follicles had higher (P≤0.01) follicular fluid levels of miR-145 and miR-378. In Experiment 2, follicular fluid and granulosa cells were aspirated from dominant follicles before (DO) and 24 h after (L) administration of an ovulatory dose of hCG (n=5 mares/group). Relative to DO follicles, L follicles had higher follicular fluid levels of progesterone (P=0.05) and lower granulosa cell levels of CYP19A1 and LHCGR (P<0.005). Levels of miR-21, miR-132, miR-212, and miR-224 were increased (P<0.05) in L follicles; this was associated with reduced expression of the putative miRNA targets, PTEN, RASA1, and SMAD4. These novel results may indicate a physiological involvement of miR-21, miR-145, miR-224, miR-378, miR-132, and miR-212 in the regulation of cell survival, steroidogenesis, and differentiation during follicle selection and ovulation in the monovular ovary.


Assuntos
Cavalos/fisiologia , MicroRNAs/fisiologia , Folículo Ovariano/metabolismo , Animais , Gonadotropina Coriônica/fisiologia , Dinoprostona/metabolismo , Feminino , Líquido Folicular/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Distribuição Aleatória , Esteroides/fisiologia
7.
Br J Cancer ; 108(9): 1830-7, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23591196

RESUMO

BACKGROUND: Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before. METHODS: In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase-PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14(ARF) and the proliferation marker Ki-67. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth. RESULTS: In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04-3.40; P=0.043) and cancer-specific survival (HR=2.0; CI=1.1-3.8; P=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (P=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (P<0.05). CONCLUSION: This is the first study of the expression pattern and distribution of spinophilin in HCC. According to our data, the loss of spinophilin is associated with higher proliferation and might be useful as a prognostic marker in patients with HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D2/biossíntese , Intervalo Livre de Doença , Feminino , Células Hep G2 , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Masculino , Proteínas dos Microfilamentos/genética , Proteínas do Tecido Nervoso/genética , Prognóstico , Modelos de Riscos Proporcionais , Interferência de RNA , RNA Interferente Pequeno , Taxa de Sobrevida , Proteína Supressora de Tumor p14ARF/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética
8.
Plant Signal Behav ; 8(2): e23091, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23299423

RESUMO

On the surface of healthy land plants (embryophytes), numerous non-pathogenic bacteria have been discovered and described. Among these epiphytic microbes, pink-pigmented facultative methylotrophic microbes of the genus Methylobacterium are of special significance, because these microorganisms consume methanol emitted via the stomatal pores and secrete growth-promoting phytohormones. Methylobacterium funariae, Schauer and Kutschera 2011, a species isolated in our lab from the common cord moss, described as a nova species in this journal, was recently characterized for a second time as a "new taxon" under a different name, "M. bullatum." Based on a phylogenetic analysis, we show that these taxa are identical. In addition, we provide novel information on the exact cell size, and describe the correct type locality of this bacterial species, which was classified as a phytosymbiont. Finally, we discuss the hypothesis that certain methylobacteria may preferentially colonize bryophytes. With reference to our recent discovery that thalli of ferns form, like liverworts and moss protonemata, associations with methylobacteria, we argue that the haploid phase of cryptogames are preferred host organisms of these pink-pigmented microbial phytosymbionts.


Assuntos
Briófitas/microbiologia , Methylobacterium/fisiologia , Hepatófitas/microbiologia , Methylobacterium/classificação , Filogenia
9.
Theriogenology ; 79(3): 409-16, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23199747

RESUMO

There is evidence in several species that high circulating LH concentrations can interfere with normal follicle development and ovulation. In the mare, high LH levels after induction of luteolysis with PGF(2α) have been temporally associated with an increased incidence of anovulatory follicles. We hypothesized that a premature increase in LH levels during a follicular wave in mares would disrupt normal follicle maturation leading to ovulatory dysfunction. In experiment 1, all follicles >10 mm were ablated at midestrous cycle in pony mares followed by twice daily administration of equine LH (eLH; 1.6 µg/kg body weight) or saline (vehicle; N = 8 mares per group). When a dominant follicle reached >32 mm, an ovulatory dose of hCG was given. Treatment with eLH had no effects on ovulatory responses or progesterone levels during the posttreatment luteal phase. In experiment 2, after follicle ablation, mares were treated with eLH or vehicle (as above) or were given a single injection of PGF(2α) (N = 7 mares per group), followed by aspiration of a dominant follicle when it reached >32 mm. Administration of eLH induced an increase in circulating LH levels similar to that after PGF(2α) injection. Neither PGF(2α) nor eLH administration had significant effects on follicle growth or total number of follicles in the postablation wave. However, compared with mares treated with vehicle, the preovulatory follicle in the eLH and PGF(2α) groups had lower levels of androstenedione (P = 0.03) and higher levels of insulin-like growth factor I (P = 0.03). Further, levels of prostaglandin E2 in preovulatory follicles tended to be lower in the eLH and PGF(2α) groups (P = 0.06). In conclusion, exposure of developing follicles to high LH in mares did not have apparent effects on ovulation but it induced changes in follicular fluid factor levels which might reflect a disruption in follicle and/or oocyte maturation, indicating the need to further study the implications of using PGF(2α) for the control of fertility in farm animals.


Assuntos
Cavalos/fisiologia , Hormônio Luteinizante/administração & dosagem , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Androstenodiona/análise , Animais , Gonadotropina Coriônica/administração & dosagem , Dinoprosta/administração & dosagem , Feminino , Hormônio Foliculoestimulante/sangue , Líquido Folicular/química , Fator de Crescimento Insulin-Like I/análise , Hormônio Luteinizante/sangue , Folículo Ovariano/anatomia & histologia , Ovulação/efeitos dos fármacos , Progesterona/sangue
10.
J Endocrinol ; 215(3): 323-34, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23038794

RESUMO

Although much progress has been made in the genetic dissection of biological networks involved in follicular/luteal development in the mammalian ovary, the gene regulation mechanisms involved are still poorly understood. Over the last 10 years, miRNAs have emerged as master regulators of tissue growth and differentiation in animals. However, compared with other body tissues, little is still known about the functional involvement of miRNAs in the ovary. Several studies have identified miRNA populations specifically associated with the development of follicles and corpora lutea, particularly in relation to the follicular-luteal transition, and the functional involvement of some of these miRNAs has been characterised in vitro and/or in vivo. Specifically, three different miRNAs, miR-224, miR-378 and miR-383, have shown to be involved in regulating aromatase expression during follicle development. In addition, miR-21 has been identified as promoting follicular cell survival during ovulation, and pro-angiogenic miR-17-5p and let-7b were shown to be necessary for normal development of the corpus luteum. Experimental evidence for the involvement of several other miRNAs in different aspects of follicle/luteal development has also been obtained. In addition, many of these studies exemplify the challenges associated with identifying physiologically relevant targets of ovarian miRNAs. Continuous advances in this field will be considerably facilitated by progress in understanding miRNA physiology in other body systems and will eventually lead to a much better understanding of the control of follicular/luteal development. In turn, through the potential offered by miRNA diagnostics and miRNA therapeutics, this new knowledge should bring considerable benefits to reproductive medicine.


Assuntos
Corpo Lúteo/crescimento & desenvolvimento , Corpo Lúteo/metabolismo , MicroRNAs/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Animais , Feminino , Humanos , MicroRNAs/genética
11.
Cell Death Dis ; 3: e354, 2012 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-22825472

RESUMO

According to the concept of lipotoxicity, ectopic accumulation of lipids in non-adipose tissue induces pathological changes. The most prominent effects are seen in fatty liver disease, lipid cardiomyopathy, non-insulin-dependent diabetes mellitus, insulin resistance and skeletal muscle myopathy. We used the MCK(m)-hLPL mouse distinguished by skeletal and cardiac muscle-specific human lipoprotein lipase (hLPL) overexpression to investigate effects of lipid overload in skeletal muscle. We were intrigued to find that ectopic lipid accumulation induced proteasomal activity, apoptosis and skeletal muscle damage. In line with these findings we observed reduced Musculus gastrocnemius and Musculus quadriceps mass in transgenic animals, accompanied by severely impaired physical endurance. We suggest that muscle loss was aggravated by impaired muscle regeneration as evidenced by reduced cross-sectional area of regenerating myofibers after cardiotoxin-induced injury in MCK(m)-hLPL mice. Similarly, an almost complete loss of myogenic potential was observed in C2C12 murine myoblasts upon overexpression of LPL. Our findings directly link lipid overload to muscle damage, impaired regeneration and loss of performance. These findings support the concept of lipotoxicity and are a further step to explain pathological effects seen in muscle of obese patients, patients with the metabolic syndrome and patients with cancer-associated cachexia.


Assuntos
Ácidos Graxos/metabolismo , Lipase Lipoproteica/metabolismo , Músculo Esquelético/metabolismo , Animais , Apoptose , Linhagem Celular , Creatina Quinase/genética , Creatina Quinase/metabolismo , Humanos , Lipase Lipoproteica/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mioblastos/metabolismo , Regeneração , Triglicerídeos/metabolismo
12.
Insect Mol Biol ; 21(3): 383-94, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22568680

RESUMO

Transcriptional activity of nuclear receptors is the result of transactivation capability and the concentration of the receptor protein. The concentration of ecdysteroid receptor (EcR) isoforms, constitutively expressed in mammalian CHO cells, is dependent on a number of factors. As shown previously, ligand binding stabilizes receptor protein concentration. In this paper, we investigate the degradation of EcR isoforms and provide evidence that N-terminal degradation is modulated by isoform-specific ubiquitination sites present in the A/B domains of EcR-A and -B1. This was demonstrated by the increase in EcR concentration by treatment with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), an inhibitor of ubiquitin-mediated proteasomal degradation and by deletion of ubiquitination sites. In addition, EcR is degraded by the peptidyl-dipeptidase cathepsin B (CatB) and the endopeptidase cathepsin S (CatS) at the C-terminus in an isoform-specific manner, despite identical C-termini. Ubiquitin-proteasome-mediated degradation and the proteolytic action are modulated by heterodimerization with Ultraspiracle (USP). The complex regulation of receptor protein concentration offers an additional opportunity to regulate transcriptional activity in an isoform- and target cell-specific way and allows the temporal limitation of hormone action.


Assuntos
Cisteína Proteases/metabolismo , Mamíferos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Receptores de Esteroides/química , Receptores de Esteroides/metabolismo , Treonina/metabolismo , Sequência de Aminoácidos , Animais , Western Blotting , Células CHO , Calpaína/antagonistas & inibidores , Calpaína/metabolismo , Catepsinas/antagonistas & inibidores , Catepsinas/metabolismo , Cricetinae , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Leupeptinas/farmacologia , Dados de Sequência Molecular , Oligopeptídeos/farmacologia , Inibidores de Proteases/farmacologia , Inibidores de Proteassoma , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Multimerização Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína , Proteólise/efeitos dos fármacos , Receptores de Esteroides/genética , Treonina/antagonistas & inibidores , Transcrição Gênica/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos
13.
Eur J Radiol ; 81(6): 1211-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21444168

RESUMO

INTRODUCTION: Achilles tendon ruptures, especially ruptures caused by pathologic conditions and also by achillotendinitis are often attributed to the alleged hypovascularisation of the Achilles tendon. Anatomic studies often mention an avascular plane. The purpose of this study was to re-investigate the arterial supply of the Achilles tendon. MATERIAL AND METHODS: Lower legs of 28 anatomic specimen were injected with a radiologic contrast agent and subsequently an arterial angiography was performed. Afterwards the legs were embalmed and later anatomically dissected. The origin of arteries entering the paratenon of the tendo calcanei branching off from either the anterior (TA) or the posterior tibial artery (TP) was determined. The distance between the points of commencement of these nutrient arteries and a specific reference point, i.e. the insertion of the Achilles tendon into the tuber calcanei, was measured digitally on the radiographs and again with a slide-gauge on the dissected specimens. RESULTS: As revealed by angiographic analysis, the TA gave off 5 vessels (v) at a frequency and median distance to the tuber calcanei (in cm) of v1: 50%, 6.01 cm; v2: 39.3%, 7.88 cm; v3: 35.7%, 9.71 cm; v4: 17.9%, 12.7 cm; v5: 10.7%, 14.6 cm. The TP contributed to the arterial supply of the Achilles tendon by means of 7 inserting arteries branching off at a frequency and mean distances of v1: 67.9%, 4.53 cm; v2: 60.7%, 6.97 cm, v3: 50%, 9.58 cm; v4: 35.7%, 10.89 cm; v5: 25%, 12.65 cm; v6: 10.7%, 16.94 cm; v7: 3.6%, 18.7 cm proximal to the tuber calcanei. However, due to the small diameter of these branches, by anatomic dissection no nutrient arteries commencing from the TA could be detected. On the other hand, a maximum of 7 vessels originating from the TP, larger than the former vessels, had been also revealed by anatomic dissection (frequency and mean distances, v1: 100%, 6.8 cm; v2: 82.1%, 7.7 cm; v3: 71.4%, 9.5cm; v4: 35.7%, 11.3 cm; v5: 17.9%, 9.9 cm; v6: 7.1, 10.5 cm; v7: 3.6%, 12.0 cm). CONCLUSION: A dense net of small arteries inserts into the paratenon of the Achilles tendon in its lower 20 cm. The angiographic method was more specific and showed vessels that could not be identified as arteries originating from the TA by macroscopic anatomic dissection.


Assuntos
Tendão do Calcâneo/irrigação sanguínea , Traumatismos dos Tendões/diagnóstico por imagem , Traumatismos dos Tendões/cirurgia , Angiografia , Cadáver , Meios de Contraste/administração & dosagem , Humanos , Iohexol/administração & dosagem , Iohexol/análogos & derivados , Ruptura
14.
Insect Mol Biol ; 20(6): 701-11, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21895819

RESUMO

Transcriptional activity of nuclear receptors is the result of transactivation capability and receptor protein concentration. The concentration of ecdysteroid receptor (EcR) constitutively expressed in vertebrate cells varies depending on the isoforms. Besides ligand binding and heterodimerization with ultraspiracle (USP), which stabilizes receptor protein concentration, degradation is regulated by interaction of the receptor complex with different ecdysteroid response elements (EcREs). Coexpression of EcREs significantly reduces ecdysteroid receptor concentration depending on the type of EcRE. Transcriptional activity and interaction with hormone response elements (HREs) as determined by Electrophoretic Mobility Shift Assay (EMSA) are often inversely related to receptor protein concentration. The complex regulation of receptor protein concentration offers an additional opportunity to regulate transcriptional activity in an isoform- and target cell-specific manner and allows the temporal limitation of hormone action.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Receptores de Esteroides/metabolismo , Elementos de Resposta , Fatores de Transcrição/metabolismo , Animais , Células CHO , Cricetinae , DNA/metabolismo , Drosophila , Técnicas de Transferência de Genes , Multimerização Proteica
15.
Plant Signal Behav ; 6(4): 510-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21673511

RESUMO

Land plants (embryophytes) evolved in the presence of prokaryotic microbes. As a result, numerous mutually beneficial associations (symbioses) developed that can be analyzed using a variety of methods. Here we describe the isolation and characterization of a new pink-pigmented facultatively methylotrophic symbiotic bacterium of the genus Methylobacterium (laboratory strain F3.2) that was isolated from the gametophytic phylloids of the common cord moss Funaria hygrometrica Hedw. Plantlets were collected in the field and analyzed in the laboratory. Colonies of methylobacteria were obtained by the agar-impression-method. Based on its unique phenotype (the bacterial cells are characterized by fimbriae-like appendages), a comparative 16S rRNA gene (DNA) sequence analysis, and an average DNA-DNA hybridization value of 8,4 %, compared with its most closely related sister taxon, this isolate is described as a new species, Methylobacterium funariae sp. nov. (type strain F3.2). This new epiphytic bacterium inhabits the leaf surface of "primitive" land plants such as mosses and interacts with its host organism via the secretion of phytohormones (cytokinines, auxins). These external signals are perceived by the plant cells that divide and grow more rapidly than in the absence of their prokaryotic phytosymbionts. We suggest that M. funariae sp. nov. uses methanol emitted from the stomatal pores as principal carbon source for cell metabolism. However, our novel data indicate that, in this unique symbiotic plant-microbe interaction, the uptake of amino acids leached from the surface of the epidermal cells of the green host organism may be of importance as microbial carbon- and nitrogen-source.


Assuntos
Briófitas/microbiologia , Methylobacterium/genética , Methylobacterium/isolamento & purificação , Folhas de Planta/microbiologia , Methylobacterium/classificação , Methylobacterium/ultraestrutura , Microscopia Eletrônica de Varredura , Filogenia , Reguladores de Crescimento de Plantas/metabolismo , RNA Ribossômico 16S/genética
17.
Theriogenology ; 75(6): 1076-84, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21295833

RESUMO

This study was conducted to test the hypothesis that supplementation of growing follicles with LH during the early spring transitional period would promote the development of steroidogenically active, dominant follicles with the ability to respond to an ovulatory dose of hCG. Mares during early transition were randomly assigned to receive a subovulatory dose of equine LH (in the form of a purified equine pituitary fraction) or saline (transitional control; n = 7 mares per group) following ablation of all follicles >15 mm. Treatments were administered intravenously every 12 h from the day the largest follicle of the post-ablation wave reached 20 mm until a follicle reached >32 mm, when an ovulatory dose of hCG (3000 IU) was given. Saline-treated mares during June and July were used as ovulatory controls. In a preliminary study, injection of this pituitary fraction (eLH) to anestrus mares was followed by an increase in circulating levels of LH (P < 0.01) but not FSH (P > 0.6). Administration of eLH during early transition stimulated the growth of the dominant follicle (Group x Day, P < 0.00001), which attained diameters similar to the dominant follicle in ovulatory controls (P > 0.1). In contrast, eLH had no effect on the diameter of the largest subordinate follicle or the number of follicles >10 mm during treatment (P > 0.3). The numbers of mares that ovulated in response to hCG in transitional control, transitional eLH and ovulatory control groups (2 of 2, 3 of 5 and 7 of 7, respectively) were not significantly different (P > 0.1). However, after hCG-induced ovulation, all transitional mares returned to an anovulatory state. Circulating estradiol levels increased during the experimental period in ovulatory controls but not in transitional eLH or transitional control groups (Group x Day, P = 0.013). In addition, although progesterone levels increased after ovulation in transitional control and transitional eLH groups, levels in these two groups were lower than in the ovulatory control group after ovulation (Group, P = 0.045). In conclusion, although LH supplementation of early transitional waves beginning after the largest follicle reached 20 mm promoted growth of ovulatory-size follicles, these follicles were developmentally deficient as indicated by their reduced steroidogenic activity.


Assuntos
Cavalos , Hormônio Luteinizante/farmacologia , Folículo Ovariano/efeitos dos fármacos , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Estações do Ano
18.
Int J Syst Evol Microbiol ; 61(Pt 4): 870-876, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20495043

RESUMO

A pink-pigmented, facultatively methylotrophic bacterium, designated strain JT1(T), was isolated from a thallus of the liverwort Marchantia polymorpha L. and was analysed by using a polyphasic approach. Comparative 16S rRNA gene sequence analysis placed the strain in a clade with Methylobacterium adhaesivum AR27(T), Methylobacterium fujisawaense DSM 5686(T), Methylobacterium radiotolerans JCM 2831(T) and Methylobacterium jeotgali S2R03-9(T), with which it showed sequence similarities of 97.8, 97.7, 97.2 and 97.4 %, respectively. However, levels of DNA-DNA relatedness between strain JT1(T) and these and the type strains of other closely related species were lower than 70 %. Cells of JT1(T) stained Gram-negative and were motile, rod-shaped and characterized by numerous fimbriae-like appendages on the outer surface of their wall (density up to 200 µm(-2)). Major fatty acids were C(18 : 1)ω7c and C(16 : 0). Based on the morphological, physiological and biochemical data presented, strain JT1(T) is considered to represent a novel species of the genus Methylobacterium, for which the name Methylobacterium marchantiae sp. nov. is proposed. The type strain is JT1(T) ( = DSM 21328(T)  = CCUG 56108(T)).


Assuntos
Hepatófitas/microbiologia , Methylobacterium/classificação , Methylobacterium/isolamento & purificação , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Fímbrias Bacterianas/fisiologia , Locomoção , Methylobacterium/genética , Methylobacterium/fisiologia , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Filogenia , Pigmentos Biológicos/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Arch Clin Neuropsychol ; 25(2): 99-117, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20080833

RESUMO

Increasingly often, practitioners in neuropsychological rehabilitation centers are called upon to assess patients' fitness to drive after brain injury. There is, therefore, a need for valid and reliable psychometric test batteries that enable unsafe drivers to be identified. This article investigates the contribution of five driving-related personality traits to the prediction of fitness to drive in patients suffering from traumatic brain injuries (TBI) or strokes over and above cognitive ability traits that have already shown to be related to safe driving. A total of 178 patients suffering from either strokes or TBI participated in this study. All the participants completed a standardized psychometric test battery and subsequently took a standardized driving test. The contribution of the driving-related ability and personality traits to the prediction of fitness to drive was investigated by means of a logistic regression analysis and an artificial neural network. The results indicate that both cognitive ability and personality factors are important in predicting fitness to drive, although cognitive ability factors contribute slightly more to the prediction of patients' actual fitness to drive than personality factors. Furthermore, even though there are subtle differences in the predictive models obtained for the two subsamples (stroke and TBI patients), these differences are adequately accounted for by a more unitary model calculated by means of an artificial neural network that is capable of taking account of moderating effects between the predictor variables.


Assuntos
Condução de Veículo , Lesões Encefálicas/reabilitação , Cognição , Personalidade , Aptidão Física , Reabilitação do Acidente Vascular Cerebral , Acidentes de Trânsito , Adulto , Idoso , Exame para Habilitação de Motoristas , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Valor Preditivo dos Testes , Psicometria , Desempenho Psicomotor , Recuperação de Função Fisiológica , Centros de Reabilitação , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas
20.
Theory Biosci ; 127(1): 23-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18193314

RESUMO

Plant-associated methylobacteria of the genus Methylobacterium colonize the foliage and roots of embryophytes, living on the volatile compound methanol emitted from the cells of their host organism. In this study we analyzed these surface-dwelling pink-pigmented epiphytes in three contrasting habitats of field-grown sunflower plants (Helianthus annuus). Using the methanol-ammonium salts agar surface impression method and a polymerase chain reaction (PCR)-based assay, we document the occurrence and characterize the composition of the methylobacteria in these epiphytic habitats. In both the sun-exposed phylloplane (yellow ligulate florets; green leaves) and the moist, dark rhizoplane pink-pigmented methylobacteria were detected that are assigned to the taxa M. mesophilicum, M. extorquens, M. radiotolerans and M. sp. (un-identifiable by our methods). Considerable differences in relative species compositions were found. These data are discussed with respect to a biogeographic model of the plant surface and microbial population dynamics on leaves. In addition, methylobacteria were analyzed by microscopic techniques. We document that in sedentary colonies extracellular polymers are secreted. However, flagella, which were observed in single cells maintained in liquid cultures, are absent in these bacterial aggregates.


Assuntos
Ecossistema , Helianthus/microbiologia , Methylobacterium/crescimento & desenvolvimento , DNA Bacteriano/química , DNA Bacteriano/genética , Methylobacterium/genética , Methylobacterium/ultraestrutura , Microscopia Eletrônica de Varredura , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética
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